The Safety, Pharmacokinetics and Antitumor Activity of BGB-A317 in Combination With BGB-290 in Participants With Advanced Solid Tumors

• Sponsor: BeiGene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02660034
• Collaborator: Myriad Genetic Laboratories, Inc. (Industry)
• Enrollment: 229
• Locations: 29
• Arms: 2
• Actual Duration (Months): 55.2
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial studied the safety, pharmacokinetics, and antitumor activity of the anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) BGB-A317 (tislelizumab) in combination with the poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor BGB-290 (pamiparib) in participants with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Biological: Tislelizumab; Drug: Pamiparib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 229 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Subjects With Advanced Solid Tumors
• Actual Study Start Date: Feb 2, 2016
• Actual Primary Completion Date: Sep 9, 2020
• Actual Study Completion Date: Sep 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Dose Escalation Phase Participants received tislelizumab and pamiparib (dose escalation) until determination of the maximum tolerated dose/recommended Phase 2 dose.	Biological: Tislelizumab; Other Names: BGB-A317 ; Drug: Pamiparib; Other Names: BGB-290
Experimental: Part B: Dose Expansion Phase Participants received tislelizumab and pamiparib (dose expansion).	Biological: Tislelizumab; Other Names: BGB-A317 ; Drug: Pamiparib; Other Names: BGB-290

Outcome Measures

Primary Outcome Measures

1. Part A: Number Of Participants Experiencing Adverse Events (AEs) [From Day 1 up to 4 years and 7 months]

   An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

2. Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) [21 days following the first dose of tislelizumab and pamiparib in Cycle 1]

   DLT was defined as an AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and occurs during the first 21 days following the first dose of tislelizumab and pamiparib in Cycle 1 and meets protocol-specified criteria. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

3. Part B: Objective Response Rate (ORR) [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   ORR was defined as the percentage of participants with a best overall response of complete response (CR) and partial response (PR).

4. Part B: Progression-free Survival (PFS) [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first.

5. Part B: Duration Of Response (DOR) [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   DOR, defined as the time from the first determination of an objective response, was assessed by investigator per Response Evaluation Criteria in Solid Tumors v1.1 until the first documentation of progression or death, whichever occurred first. Results are reported only for arms with responders.

6. Part B: Disease Control Rate (DCR) [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   DCR was defined as the percentage of participants with a best overall response of CR, PR, and stable disease (SD).

7. Part B: Clinical Benefit Rate (CBR) [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks.

8. Part B: Overall Survival (OS) [From Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)]

   OS was defined as the time from the date of first dose of study drug to death due to any cause.

Secondary Outcome Measures

1. Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab [Cycle 4 Day 1 (0 hours and 4 hours) post dose]

2. Part A: Ctrough Of Pamiparib [Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)]

3. Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib [Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)]

4. Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib [Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)]

5. Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib [Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)]

6. Part A: ORR [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   ORR was defined as the percentage of participants with a best overall response of CR and PR.

7. Part A: PFS [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first.

8. Part A: DCR [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   DCR was defined as the percentage of participants with a best overall response of CR, PR, and SD.

9. Part A: CBR [Starting from Day 1 until disease progression (up to 4 years and 7 months)]

   CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks.

10. Part A: OS [Starting from Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)]

    OS was defined as the time from the date of first dose of study drug to death due to any cause.

11. Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab [Within 24 hours before the start of the first dose of tislelizumab in Cycle 1, Day 8 of Cycle 1, and Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9, and Cycle 17]

    Immunogenicity was summarized by participants who were ADA positive and developed detectable ADAs.

12. Part B: Number Of Participants Experiencing AEs [Day 1 of Cycle 1 up to 4 years and 7 months]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

13. Part B: Ctrough Of Tislelizumab [Cycle 4 Day 1 ( 0 hours and 4 hours post dose)]

    As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.

14. Part B: Maximum Observed Plasma Concentration (Cmax) Of Tislelizumab [Cycle 4 Day 1 ( 0 hours and 4 hours) post dose]

    As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.

15. Part B: Ctrough Of Pamiparib [Cycle 2 Day 1 (7 hours Post-dose)]

    As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.

16. Part B: Cmax Of Pamiparib [Cycle 2 (7 hours Post-dose)]

    As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.

17. Part B: Percentage Of Participants With ADAs For Tislelizumab [24 hours predose of Day 1 of every cycle]

    Immunogenicity was summarized by participants who developed detectable ADAs. Treatment-emergent ADAs: sum of both treatment-induced ADAs and treatment-boosted ADAs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Participants voluntarily agreed to participate by giving written informed consent.

2. Must have received standard of care in the primary treatment of their disease.

3. Participants who had the below specified histologically confirmed malignancies that had progressed to the advanced or metastatic stage:

4. In Part A, the participants must have had an advanced malignancy, including but not limited to high-grade serous cancer of the ovary, fallopian tube, or peritoneum, triple negative breast cancer, small cell lung cancer (SCLC), primary peritoneal cancer, and any tumor likely to harbor DNA damage repair deficiencies susceptible to treatment with a PARP inhibitor or likely to be responsive to a PD-1 blocker.

5. In Part B, the participants recruited to 1 of the 8 expansion arms must have had advanced solid tumors of the following types:

Arm 1: Participants with relapsed, platinum-sensitive high-grade epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) must have met the following criteria:

1. Must have had at least 2 prior platinum-containing treatments in any treatment setting.

2. Must have had platinum-sensitive recurrent disease and must not have progressed (by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1 criteria) within 6 months of the completion of the last platinum-containing line of treatment.

• Note: Participants may have received additional non-platinum-based chemotherapy for recurrence after prior last platinum-containing regimen if the criteria for platinum sensitivity were met.

1. Arm 1a: Participants with relapsed, platinum-sensitive high-grade EOC with either known deleterious or suspected deleterious germline or somatic breast cancer susceptibility gene 1/2 (BRCA1/2) mutations or with homologous recombination deficiency (HRD).

• If HRD or BRCA1/2 mutation status from archival tissue was unknown or had not been previously evaluated, then the archival tissue must have undergone tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result was BRCA1/2 or HRD positive, the participant was eligible for enrollment in Arm 1a.

1. Arm 1b: Participants with relapsed, platinum-sensitive high grade EOC who otherwise met the above criteria and were without known germline or somatic BRCA1/2 mutations and without HRD mutation.

Arm 2: Participants with triple negative breast cancer must have met the following criteria:

1. 0-1 prior platinum-containing treatment in any treatment setting.

• Note: participants could have received additional therapy after the last platinum-containing line of treatment if the other eligibility criteria were met.

1. Participants who received at least 1 prior treatment but not more than 3 prior lines of treatment in the advanced or metastatic setting.

2. Known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with documented HRD.

• If HRD or BRCA1/2 mutation status from archival tissue was unknown or had not been previously evaluated, then the archival tissue must have undergone tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result was HRD positive, then the participant was eligible for enrollment in Arm 2.

• If archival tissue was not available and the participant submitted a fresh tumor biopsy, then the diagnostic test needed to demonstrate somatic BRCA1/2 mutation or HRD positivity.

Arm 3: Participants with metastatic castration-resistant prostate cancer, including but not limited to mutations in homologous recombination (HR) pathways and/or defined by HRD algorithms, and must have met the following criteria:

1. May be either chemotherapy-naïve, but must have received prior abiraterone acetate and/or enzalutamide treatment, or have previously had no more than 2 taxane-based chemotherapy lines of treatment, including docetaxel and carbazitaxel. If docetaxel was used more than once, this was considered as 1 line of treatment.

2. At least 2 weeks since the completion of prior flutamide, bicalutamide, and nilutimide, or enzalutamide and abiraterone treatment.

3. Documented prostate cancer with one of the following:

• Surgically or medically castrated. The testosterone levels did not need to be checked if the participant had undergone surgical castration for > 4 months. Participants receiving chemical castration should have had testosterone levels checked at baseline and confirmed to be in the castrate levels (< 0.5 ng/mL or 1.735 nM). In all cases, the luteinizing hormone-releasing hormone antagonist/agonist was to be continued in these participants.

• Participants with only non-measurable bone lesions must have had disease progression based on Prostate Cancer Clinical Trials Working Group with 2 or more new lesions or have had prostate-specific antigen progression before enrolment.

1. Known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with documented HRD.

• If HRD or BRCA1/2 mutation status from archival tissue was unknown or had not been previously evaluated, then the archival tissue must have undergone tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result was HRD positive, then the participant was be eligible for enrollment in Arm 3.

• If archival tissue was not available and the participant summitted a fresh tumor biopsy, then the diagnostic test needed to demonstrate somatic BRCA1/2 mutation or HRD positivity.

Arm 4: Participants with extensive-stage disease SCLC must have met the following criteria:

1. Received at least 1 and not more than 2 prior lines of treatment; ii. At least 1 prior line of treatment must have contained a platinum agent

Arm 5: Participants with human epidermal growth factor receptor-2 (HER2)-negative gastric or gastroesophageal junction cancer must have met the following criteria:

1. May have received at least 1 and not more than 2 prior lines of treatment

Arm 6: Participants with locally advanced or metastatic urothelial (muscle-invasive bladder, ureter, urethra, or renal pelvis) cancer must have met the following criteria:

1. Received at least 1 and not more than 2 prior lines of treatment in the advanced or metastatic disease setting; ii. At least 1 prior line of treatment must have contained a platinum agent

Arm 7: Participants with advanced or metastatic pancreatic adenocarcinoma must have met the following criteria:

1. Received at least 1 but not more than 2 lines of treatment in either an advanced or metastatic setting; ii. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent; iii. Participants with known deleterious germline or somatic BRCA1/2 mutation could be considered for the study even if platinum naïve.

Arm 8: (Note: Closed to enrollment) Participants with advanced or metastatic recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix and participants with tumors known to be mismatch repair deficient or HRD positive) must have met the following criteria:

1. Participants with a complete response, partial response, or stable disease from at least 1 prior platinum-containing treatment in any treatment setting; ii. The Sponsor medical monitor would approve tumor types for Arm 8 prior to screening.

• Note: Excluded tumor types included participants with bone or soft tissue sarcoma; central nervous system (CNS) malignancies; colorectal cancer (except microsatellite instability-high colorectal cancer is permitted); cutaneous or ocular melanoma; hematologic malignancies; HER2-negative breast cancer without BRCA mutation; mesothelioma, papillary, follicular, medullary or Hürthle cell thyroid cancer; unknown primary malignancy.

1. Participants who were treated with chemotherapy or any investigational therapies, if eligible, must have completed at least 4 weeks or at least 5 half-lives (whichever is longer, but no less than 3 weeks) before the study drug administration, and all adverse events (AEs) had either returned to baseline or stabilized.

2. At least 2 weeks from palliative radiotherapy.

3. Participants must have had archival tumor tissue or agree to a tumor biopsy for mutation and biomarkers analysis unless previously discussed with Sponsor's medical monitor or its designee (fresh tumor biopsies were recommended at baseline in participants with readily accessible tumor lesions and who consented to the biopsies). Participants with ovarian, fallopian tube, primary peritoneal, or breast cancer in Part A and all participants enrolled in Part B must also have agreed to provide fresh blood sample at the baseline for the evaluation of BRCA mutations and/or confirmation of prior BRCA results or other HR deficiency mutations, even if it was previously tested.

4. Participants must have had measurable disease as defined in RECIST v1.1. Participants with metastatic castration-resistant prostate cancer and epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer may have used separate disease-specific criteria.

5. Male or female ≥ 18 years of age on the day of signing informed consent.

6. Must have had an Eastern Cooperative Oncology Group Performance Status ≤ 1.

7. Must have had a life expectancy ≥ 12 weeks.

8. Must have had adequate organ function.

9. Females of childbearing potential must have been willing to use a highly effective method of birth control for the duration of the study, and for at least 6 months after the last dose of investigational drug, and have had a negative serum pregnancy test within 7 days of the first dose of study drug(s).

10. Non-sterile males and their female partners must have been willing to use a highly effective method of birth control for the duration of the study and for at least 6 months after the last dose of investigational drug. Nonsterile males must have avoided sperm donation for the duration of the study and for at least 6 months after last study drug.

11. Females must have agreed not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.

Key Exclusion Criteria:

1. Participants with ovarian cancer who have platinum-resistant/refractory disease, defined as progressive disease at the first tumor assessment while receiving platinum-containing chemotherapy.

2. Participant had history of severe hypersensitivity reactions to other mAbs.

3. Any major surgery within 28 days before first dose of study drugs.

4. Prior allogeneic stem cell transplantation or organ transplantation.

5. Participants with toxicities (as a result of prior anticancer therapy) that had not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (for example, alopecia, neuropathy and specific laboratory abnormalities).

6. Concurrent participation in another clinical trial.

7. Prior malignancy within the previous 2 years except for locally curable non-melanoma dermatologic cancers that had been apparently cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the skin, cervix, breast, bladder, or prostate.

8. Symptomatic CNS metastasis or leptomeningeal disease. Note: Baseline magnetic resonance imaging of the brain and spinal cord was required for SCLC participants enrolled in Arm 4 if they had a history of CNS disease.

Note: Participants with previously treated CNS metastatic disease were eligible for any arm if CNS metastatic disease was asymptomatic, clinically stable, and did not require corticosteroids or anticonvulsants within a minimum of 4 weeks of enrollment.

1. Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or PARP.

2. Active autoimmune diseases or history of autoimmune diseases that may have relapsed.

Note: Participants with the following diseases were not excluded and may have proceeded to further screening:

1. Controlled Type I diabetes;

2. Hypothyroidism managed with no treatment other than with hormone replacement therapy;

3. Controlled celiac disease;

4. Skin diseases not requiring systemic treatment (for example, vitiligo, psoriasis, alopecia);

5. Any other disease that was not expected to recur in the absence of external triggering factors.

6. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 2 weeks of the study drug administration.

Note: Participants who were currently or had previously been on any of the following steroid regimens were not excluded:

1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent);

2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption;

3. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (for example, for contrast dye allergy) or for the treatment of a non-autoimmune condition (for example, delayed-type hypersensitivity reaction caused by contact allergen).

4. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, et cetera.

5. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, et cetera.

6. History of non-viral hepatitis or cirrhosis.

7. Positive human immunodeficiency virus status.

8. A known history of hepatitis B virus or hepatitis C virus infection.

9. History of alcohol abuse.

10. Underlying medical conditions or alcohol or drug abuse or dependence that, in the investigator's opinion, would be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs; or insufficient compliance during the study according to investigator's judgement.

11. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening, or otherwise altering the product formulation. Participants should not have had gastrointestinal illnesses that would have precluded the absorption of pamiparib, which was an oral agent.

12. Had been administered a live vaccine within 4 weeks (28 days) of initiation of study therapy.

13. Any of the following cardiovascular criteria:

14. Current evidence of cardiac ischemia;

15. Current symptomatic pulmonary embolism;

16. Acute myocardial infarction ≤ 6 months prior to Day 1;

17. Heart failure of New York Heart Association Classification III or IV ≤ 6 months prior to Day 1;

18. Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to Day 1;

19. History of cerebrovascular accident within 6 months before first dose of study drugs.

20. Use or had anticipated need for food or drugs known to be strong or moderate cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers ≤ 10 days (or ≤ 5 half-lives, whichever is shorter) prior to Day 1.

Note: Other protocol-defined Inclusion/Exclusion criteria may have applied.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Oncology Hematology	Scottsdale	Arizona	United States	85258
2	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
3	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
4	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
5	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
6	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
7	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
8	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
9	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
10	Texas Oncology	Dallas	Texas	United States	75246
11	Texas Oncology	Tyler	Texas	United States	75702
12	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
13	The Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
14	Mid North Coast Cancer Institute	Coffs Harbour	New South Wales	Australia	2450
15	Calvary Mater Newcastle	Newcastle	New South Wales	Australia	2298
16	Westmead Hospital	Parramatta	New South Wales	Australia
17	Prince of Wales	Randwick	New South Wales	Australia
18	Northern Cancer Institute	St Leonards	New South Wales	Australia	2065
19	Icon Cancer Care	Brisbane	Queensland	Australia	4101
20	Monash Health	Clayton	Victoria	Australia
21	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia
22	Linear Clinical Research Ltd	Nedlands	Western Australia	Australia
23	Institut Gustave Roussy	Paris		France	94800
24	Centre Eugene Marquis	Rennes		France	35042
25	Auckland City Hospital	Auckland		New Zealand	1023
26	Capital and Coast District Health Board	Wellington		New Zealand	6021
27	Hospital Universitario Vall d'Hebrón	Barcelona		Spain	08035
28	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
29	Sarah Cannon Research Institute	London		United Kingdom	W1G 6AD

Sponsors and Collaborators

• BeiGene
• Myriad Genetic Laboratories, Inc.

Investigators

• Principal Investigator: Study Director, BeiGene

Study Documents (Full-Text)

• Study Protocol - Sep 18, 2018
• Statistical Analysis Plan - Sep 4, 2020

More Information

Publications

None provided.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT02660034
• Other Study ID Numbers: BGB-A317/BGB-290_Study_001; 2017-003580-35
• First Posted: Jan 21, 2016
• Last Update Posted: Dec 6, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by BeiGene: Dose Escalation; Dose Expansion; BGB-A317; BGB-290; Tislelizumab; Pamiparib
• Additional relevant MeSH terms: Neoplasms

Study Results

Participant Flow

Recruitment Details	Part A: A total of 49 participants with advanced solid tumors were enrolled in Part A of the study (dose escalation phase) at a total of 5 sites or community oncology centers in Australia. Part B: A total of 180 participants with advanced solid tumors were enrolled in Part B of the study (dose expansion phase).

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants received tislelizumab (2 milligrams/kilogram [mg/kg] once every 3 weeks [Q3W] intravenously [IV]) with pamiparib (20 mg twice daily) (dose escalation) until determination of the maximum tolerated dose/recommended Phase 2 dose (MTD/RP2D).	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants with relapsed, platinum-sensitive, high-grade epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) with either known germline or somatic breast cancer susceptibility gene 1/2 (BRCA1/2) mutations or with homologous recombination deficiency (HRD) received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with triple negative breast cancer (TNBC) with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with metastatic castration-resistant prostate cancer (mCRPC) with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease small cell lung cancer (SCLC) treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with human epidermal growth factor receptor-2 (HER2)-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a poly (ADP-ribose) polymerase (PARP) inhibitor and a programmed cell death 1 (PD-1) inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be mismatch repair [MMR] deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Period Title: Overall Study
STARTED	12	12	6	13	6	23	23	19	20	23	20	21	21	10
Received At Least 1 Dose of Study Drug(s)	12	12	6	13	6	23	23	19	20	23	20	21	21	10
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	12	12	6	13	6	23	23	19	20	23	20	21	21	10

Baseline Characteristics

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8	Total
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.	Total of all reporting groups
Overall Participants	12	12	6	13	6	23	23	19	20	23	20	21	21	10	229
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.9 (9.39)	58.6 (9.52)	54.5 (11.27)	61.8 (11.42)	64.3 (5.96)	59.5 (10.71)	69.1 (8.68)	50.4 (12.41)	68.0 (8.89)	64.2 (9.87)	58.5 (13.71)	68.9 (10.45)	63.3 (9.11)	60.1 (16.20)	62.3 (11.7)
Sex: Female, Male (Count of Participants)
Female	9 75%	11 91.7%	5 83.3%	12 92.3%	5 83.3%	23 100%	23 100%	19 100%	0 0%	10 43.5%	3 15%	6 28.6%	9 42.9%	5 50%	140 61.1%
Male	3 25%	1 8.3%	1 16.7%	1 7.7%	1 16.7%	0 0%	0 0%	0 0%	20 100%	13 56.5%	17 85%	15 71.4%	12 57.1%	5 50%	89 38.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	1 4.3%	1 4.3%	2 10.5%	1 5%	0 0%	1 5%	1 4.8%	0 0%	0 0%	7 3.1%
Not Hispanic or Latino	12 100%	12 100%	6 100%	13 100%	6 100%	22 95.7%	22 95.7%	16 84.2%	18 90%	21 91.3%	17 85%	17 81%	19 90.5%	9 90%	210 91.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.3%	1 5%	2 8.7%	2 10%	3 14.3%	2 9.5%	1 10%	12 5.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 16.7%	0 0%	1 16.7%	2 15.4%	0 0%	2 8.7%	0 0%	0 0%	0 0%	2 8.7%	1 5%	0 0%	0 0%	2 20%	12 5.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	1 4.3%	0 0%	0 0%	1 5%	1 4.3%	0 0%	0 0%	0 0%	0 0%	3 1.3%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5%	0 0%	2 9.5%	0 0%	3 1.3%
White	10 83.3%	12 100%	5 83.3%	11 84.6%	6 100%	20 87%	23 100%	17 89.5%	18 90%	18 78.3%	16 80%	18 85.7%	19 90.5%	8 80%	201 87.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 10.5%	1 5%	2 8.7%	2 10%	3 14.3%	0 0%	0 0%	10 4.4%

Outcome Measures

1. Primary Outcome

Title	Part A: Number Of Participants Experiencing Adverse Events (AEs)
Description	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	From Day 1 up to 4 years and 7 months

Outcome Measure Data

Analysis Population Description

The safety analysis set (SAF) included all participants (both parts) who received at least one dose of tislelizumab and/or pamiparib.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Count of Participants [Participants]	12 100%	12 100%	6 100%	13 100%	6 100%

2. Primary Outcome

Title	Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)
Description	DLT was defined as an AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and occurs during the first 21 days following the first dose of tislelizumab and pamiparib in Cycle 1 and meets protocol-specified criteria. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	21 days following the first dose of tislelizumab and pamiparib in Cycle 1

Outcome Measure Data

Analysis Population Description

SAF included all participants (both parts) who received at least one dose of tislelizumab and/or pamiparib.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Count of Participants [Participants]	0 0%	0 0%	0 0%	2 15.4%	2 33.3%

3. Primary Outcome

Title	Part B: Objective Response Rate (ORR)
Description	ORR was defined as the percentage of participants with a best overall response of complete response (CR) and partial response (PR).
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known germline or somatic BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	23	23	19	20	23	20	21	21	10
Count of Participants [Participants]	7 58.3%	3 25%	9 150%	4 30.8%	2 33.3%	2 8.7%	6 26.1%	0 0%	3 15%

4. Primary Outcome

Title	Part B: Progression-free Survival (PFS)
Description	PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first.
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	23	23	19	20	23	20	21	21	7
Median (95% Confidence Interval) [month]	8.2	3.5	8.4	10.4	2.0	2.1	3.5	1.9	2.2

5. Primary Outcome

Title	Part B: Duration Of Response (DOR)
Description	DOR, defined as the time from the first determination of an objective response, was assessed by investigator per Response Evaluation Criteria in Solid Tumors v1.1 until the first documentation of progression or death, whichever occurred first. Results are reported only for arms with responders.
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	7	3	9	4	2	2	6	3
Median (95% Confidence Interval) [months]	11.2	6.2	17.1	NA	6.2	NA	NA	NA

6. Primary Outcome

Title	Part B: Disease Control Rate (DCR)
Description	DCR was defined as the percentage of participants with a best overall response of CR, PR, and stable disease (SD).
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	23	23	19	20	23	20	21	21	10
Count of Participants [Participants]	21 175%	11 91.7%	14 233.3%	15 115.4%	7 116.7%	7 30.4%	12 52.2%	2 10.5%	4 20%

7. Primary Outcome

Title	Part B: Clinical Benefit Rate (CBR)
Description	CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks.
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	23	23	19	20	23	20	21	21	10
Count of Participants [Participants]	15 125%	7 58.3%	11 183.3%	10 76.9%	4 66.7%	4 17.4%	8 34.8%	1 5.3%	3 15%

8. Primary Outcome

Title	Part B: Overall Survival (OS)
Description	OS was defined as the time from the date of first dose of study drug to death due to any cause.
Time Frame	From Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	23	23	19	20	23	20	21	21	10
Median (95% Confidence Interval) [month]	20.9	18.7	15.8	21.2	6.9	7.4	8.4	4.1	4.1

9. Secondary Outcome

Title	Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab
Time Frame	Cycle 4 Day 1 (0 hours and 4 hours) post dose

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	5	8	4	7	2
Cycle 4 Day 1 (Pre-dose)	23530 (48.02)	26040 (58.04)	26160 (23.69)	30330 (58.28)	53700 (81.62)
Cycle 4 Day 1 (4 h)	74260 (20.70)	66250 (47.28)	69020 (16.47)	104300 (35.31)	119600 (33.83)

10. Secondary Outcome

Title	Part A: Ctrough Of Pamiparib
Time Frame	Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Cycle 2 Day 1 (Pre-dose)	772.9 (164.6)	1258 (62.13)	1209 (42.18)	1876 (60.41)	2754 (48.69)
Cycle 2 Day 1 (7 h)	824.8 (130.6)	1469 (38.14)	1717 (55.56)	2070 (47.36)	2969 (48.77)

11. Secondary Outcome

Title	Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib
Time Frame	Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Number [nanogram/milliliter]	1457	2497	2985	2586	3189

12. Secondary Outcome

Title	Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib
Time Frame	Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Median (95% Confidence Interval) [hour]	1.0	1.1	1.0	1.9	2.0

13. Secondary Outcome

Title	Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib
Time Frame	Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter]	494 (130)	1170 (66)	1151 (97)	2135 (39)	2554 (2.5)

14. Secondary Outcome

Title	Part A: ORR
Description	ORR was defined as the percentage of participants with a best overall response of CR and PR.
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

EFF included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Count of Participants [Participants]	1 8.3%	3 25%	0 0%	3 23.1%	3 50%

15. Secondary Outcome

Title	Part A: PFS
Description	PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first.
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

EFF included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Median (95% Confidence Interval) [Days]	64	77	190	107	373

16. Secondary Outcome

Title	Part A: DCR
Description	DCR was defined as the percentage of participants with a best overall response of CR, PR, and SD.
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Count of Participants [Participants]	3 25%	6 50%	5 83.3%	7 53.8%	5 83.3%

17. Secondary Outcome

Title	Part A: CBR
Description	CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks.
Time Frame	Starting from Day 1 until disease progression (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Median (Standard Deviation) [week]	2 (16.7)	5 (41.7)	4 (66.7)	4 (30.8)	4 (66.7)

18. Secondary Outcome

Title	Part A: OS
Description	OS was defined as the time from the date of first dose of study drug to death due to any cause.
Time Frame	Starting from Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)

Outcome Measure Data

Analysis Population Description

The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Median (95% Confidence Interval) [Days]	259	413	NA	434	NA

19. Secondary Outcome

Title	Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab
Description	Immunogenicity was summarized by participants who were ADA positive and developed detectable ADAs.
Time Frame	Within 24 hours before the start of the first dose of tislelizumab in Cycle 1, Day 8 of Cycle 1, and Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9, and Cycle 17

Outcome Measure Data

Analysis Population Description

The Antidrug Antibody (ADA) Analysis Set included participants who received ≥ 1 dose of study drug.

Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1	Part A: Dose Escalation Phase - Cohort 2	Part A: Dose Escalation Phase - Cohort 3	Part A: Dose Escalation Phase - Cohort 4	Part A: Dose Escalation Phase - Cohort 5
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.	Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.
Measure Participants	12	12	6	13	6
Count of Participants [Participants]	3 25%	1 8.3%	0 0%	1 7.7%	0 0%

20. Secondary Outcome

Title	Part B: Number Of Participants Experiencing AEs
Description	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	Day 1 of Cycle 1 up to 4 years and 7 months

Outcome Measure Data

Analysis Population Description

SAF will include all participants (both parts) who received at least one dose of tislelizumab and/or pamiparib.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	23	23	19	20	23	20	21	21	10
Count of Participants [Participants]	23 191.7%	23 191.7%	19 316.7%	20 153.8%	23 383.3%	20 87%	21 91.3%	21 110.5%	9 45%

21. Secondary Outcome

Title	Part B: Ctrough Of Tislelizumab
Description	As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time Frame	Cycle 4 Day 1 ( 0 hours and 4 hours post dose)

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part B: Dose Expansion Phase
Arm/Group Description	Participants received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.
Measure Participants	180
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter]	46060 (36)

22. Secondary Outcome

Title	Part B: Maximum Observed Plasma Concentration (Cmax) Of Tislelizumab
Description	As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time Frame	Cycle 4 Day 1 ( 0 hours and 4 hours) post dose

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part B: Dose Expansion Phase
Arm/Group Description	Participants received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily
Measure Participants	180
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter]	99408 (20)

23. Secondary Outcome

Title	Part B: Ctrough Of Pamiparib
Description	As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time Frame	Cycle 2 Day 1 (7 hours Post-dose)

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.

Arm/Group Title	Part B: Dose Expansion Phase
Arm/Group Description	Participants received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.
Measure Participants	180
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter]	1161 (80)

24. Secondary Outcome

Title	Part B: Cmax Of Pamiparib
Description	As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time Frame	Cycle 2 (7 hours Post-dose)

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab..

Arm/Group Title	Part B: Dose Expansion Phase
Arm/Group Description	Participants received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.
Measure Participants	180
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter]	1850 (63)

25. Secondary Outcome

Title	Part B: Percentage Of Participants With ADAs For Tislelizumab
Description	Immunogenicity was summarized by participants who developed detectable ADAs. Treatment-emergent ADAs: sum of both treatment-induced ADAs and treatment-boosted ADAs.
Time Frame	24 hours predose of Day 1 of every cycle

Outcome Measure Data

Analysis Population Description

The Antidrug Antibody (ADA) Analysis Set included participants who received ≥ 1 dose of study drug.

Arm/Group Title	Part B: Dose Expansion Phase - Arm 1a	Part B: Dose Expansion Phase - Arm 1b	Part B: Dose Expansion Phase - Arm 2	Part B: Dose Expansion Phase - Arm 3	Part B: Dose Expansion Phase - Arm 4	Part B: Dose Expansion Phase - Arm 5	Part B: Dose Expansion Phase - Arm 6	Part B: Dose Expansion Phase - Arm 7	Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.	Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.	Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.	Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.	Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.	Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve.	Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
Measure Participants	19	18	16	18	21	19	19	17	9
Treatment-emergent ADA	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	1 4.3%	0 0%	0 0%	2 10%
Treatment-boosted ADA	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Treatment-induced ADA	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	1 4.3%	0 0%	0 0%	2 10%
Persistent ADA Response	0 0%	0 0%	0 0%	0 0%	0 0%	1 4.3%	0 0%	0 0%	0 0%
Transient ADA Response	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	0 0%	0 0%	0 0%	2 10%
NAb Positive	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Day 1 through 4 years and 7 months
Arm/Group Title	Part A: Dose Escalation Phase - Cohort 1		Part A: Dose Escalation Phase - Cohort 2		Part A: Dose Escalation Phase - Cohort 3		Part A: Dose Escalation Phase - Cohort 4		Part A: Dose Escalation Phase - Cohort 5		Part B: Dose Expansion Phase - Arm 1a		Part B: Dose Expansion Phase - Arm 1b		Part B: Dose Expansion Phase - Arm 2		Part B: Dose Expansion Phase - Arm 3		Part B: Dose Expansion Phase - Arm 4		Part B: Dose Expansion Phase - Arm 5		Part B: Dose Expansion Phase - Arm 6		Part B: Dose Expansion Phase - Arm 7		Part B: Dose Expansion Phase - Arm 8
Arm/Group Description	Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D.		Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.		Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.		Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D.		Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D.		Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.		Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy.		Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment.		Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment.		Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.		Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment.		Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily.		Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum-naïve.		Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm.
All Cause Mortality
	Part A: Dose Escalation Phase - Cohort 1		Part A: Dose Escalation Phase - Cohort 2		Part A: Dose Escalation Phase - Cohort 3		Part A: Dose Escalation Phase - Cohort 4		Part A: Dose Escalation Phase - Cohort 5		Part B: Dose Expansion Phase - Arm 1a		Part B: Dose Expansion Phase - Arm 1b		Part B: Dose Expansion Phase - Arm 2		Part B: Dose Expansion Phase - Arm 3		Part B: Dose Expansion Phase - Arm 4		Part B: Dose Expansion Phase - Arm 5		Part B: Dose Expansion Phase - Arm 6		Part B: Dose Expansion Phase - Arm 7		Part B: Dose Expansion Phase - Arm 8
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		9/12 (75%)		2/6 (33.3%)		10/13 (76.9%)		3/6 (50%)		13/23 (56.5%)		14/23 (60.9%)		10/19 (52.6%)		9/20 (45%)		21/23 (91.3%)		17/20 (85%)		15/21 (71.4%)		20/21 (95.2%)		8/10 (80%)
Serious Adverse Events
	Part A: Dose Escalation Phase - Cohort 1		Part A: Dose Escalation Phase - Cohort 2		Part A: Dose Escalation Phase - Cohort 3		Part A: Dose Escalation Phase - Cohort 4		Part A: Dose Escalation Phase - Cohort 5		Part B: Dose Expansion Phase - Arm 1a		Part B: Dose Expansion Phase - Arm 1b		Part B: Dose Expansion Phase - Arm 2		Part B: Dose Expansion Phase - Arm 3		Part B: Dose Expansion Phase - Arm 4		Part B: Dose Expansion Phase - Arm 5		Part B: Dose Expansion Phase - Arm 6		Part B: Dose Expansion Phase - Arm 7		Part B: Dose Expansion Phase - Arm 8
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		5/12 (41.7%)		3/6 (50%)		6/13 (46.2%)		5/6 (83.3%)		6/23 (26.1%)		16/23 (69.6%)		7/19 (36.8%)		8/20 (40%)		14/23 (60.9%)		10/20 (50%)		13/21 (61.9%)		8/21 (38.1%)		8/10 (80%)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		2/19 (10.5%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Cardiac disorders
Atrial fibrillation	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Supraventricular tachycardia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		1/21 (4.8%)		0/10 (0%)
Cardiac failure	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Coronary artery occlusion	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Myocardial infarction	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Myocarditis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Endocrine disorders
Hypophysitis	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Gastrointestinal disorders
Ascites	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		1/23 (4.3%)		2/23 (8.7%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		2/21 (9.5%)		0/10 (0%)
Diarrhoea	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Intestinal obstruction	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Malignant gastrointestinal obstruction	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Nausea	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Small intestinal obstruction	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		2/23 (8.7%)		4/23 (17.4%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Vomiting	0/12 (0%)		0/12 (0%)		0/6 (0%)		2/13 (15.4%)		1/6 (16.7%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Constipation	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		1/21 (4.8%)		2/10 (20%)
Abdominal pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Abdominal pain upper	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Dysphagia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Gastritis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Gastritis erosive	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Gastrooesophageal reflux disease	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Large intestinal obstruction	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
General disorders
General physical health deterioration	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Pyrexia	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		1/20 (5%)		1/23 (4.3%)		0/20 (0%)		2/21 (9.5%)		0/21 (0%)		0/10 (0%)
Fatigue	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		1/20 (5%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Asthenia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Non-cardiac chest pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hepatobiliary disorders
Autoimmune hepatitis	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		1/23 (4.3%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hepatitis	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		2/23 (8.7%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Immune-mediated hepatitis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		2/23 (8.7%)		3/23 (13%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Malignant biliary obstruction	0/12 (0%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Bile duct obstruction	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hepatic failure	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Jaundice	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Infections and infestations
Abdominal sepsis	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Escherichia bacteraemia	0/12 (0%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Lower respiratory tract infection viral	0/12 (0%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pneumocystis jirovecii pneumonia	0/12 (0%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pneumonia	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		1/19 (5.3%)		1/20 (5%)		2/23 (8.7%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pyoderma streptococcal	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Urinary tract infection	0/12 (0%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		2/21 (9.5%)		0/21 (0%)		0/10 (0%)
Sepsis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Biliary tract infection	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Corneal abscess	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Gastroenteritis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Osteomyelitis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Periorbital cellulitis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pneumococcal infection	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pneumonia klebsiella	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Pulmonary sepsis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Sinobronchitis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Lower respiratory tract infection	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		2/19 (10.5%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Injury, poisoning and procedural complications
Lumbar vertebral fracture	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Femur fracture	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Fall	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Gastroenteritis radiation	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Humerus fracture	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Post procedural haemorrhage	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Procedural pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Investigations
Alanine aminotransferase increased	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Aspartate aminotransferase increased	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Blood bilirubin increased	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Troponin T increased	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Metabolism and nutrition disorders
Hypomagnesaemia	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Dehydration	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		2/20 (10%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hypoglycaemia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Cachexia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Diabetic ketoacidosis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Hypokalaemia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Malnutrition	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Flank pain	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Polymyalgia rheumatica	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Back pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		1/19 (5.3%)		0/20 (0%)		1/23 (4.3%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Musculoskeletal chest pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Groin pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Osteonecrosis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pathological fracture	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Squamous cell carcinoma of skin	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Nervous system disorders
Spinal cord compression	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		3/20 (15%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Headache	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Cerebrovascular accident	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Depressed level of consciousness	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Hemiplegia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Seizure	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Syncope	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Transient ischaemic attack	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Psychiatric disorders
Delirium	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Substance-induced psychotic disorder	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Renal and urinary disorders
Acute kidney injury	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		2/21 (9.5%)		1/21 (4.8%)		0/10 (0%)
Ureteric obstruction	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Haematuria	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Nephrolithiasis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Urinary tract obstruction	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Reproductive system and breast disorders
Pelvic pain	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Vaginal haemorrhage	0/9 (0%)		0/11 (0%)		0/5 (0%)		1/12 (8.3%)		0/5 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/0 (NaN)		0/10 (0%)		0/3 (0%)		0/6 (0%)		0/9 (0%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pleural effusion	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Pulmonary embolism	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		2/20 (10%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Pneumonitis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Dyspnoea	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		2/23 (8.7%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pleuritic pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pneumonia aspiration	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pneumothorax	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Respiratory distress	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Respiratory failure	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Rash macular	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Rash maculo-papular	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Vascular disorders
Hypotension	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Embolism arterial	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Haematoma	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Superior vena cava occlusion	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Superior vena cava syndrome	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Dose Escalation Phase - Cohort 1		Part A: Dose Escalation Phase - Cohort 2		Part A: Dose Escalation Phase - Cohort 3		Part A: Dose Escalation Phase - Cohort 4		Part A: Dose Escalation Phase - Cohort 5		Part B: Dose Expansion Phase - Arm 1a		Part B: Dose Expansion Phase - Arm 1b		Part B: Dose Expansion Phase - Arm 2		Part B: Dose Expansion Phase - Arm 3		Part B: Dose Expansion Phase - Arm 4		Part B: Dose Expansion Phase - Arm 5		Part B: Dose Expansion Phase - Arm 6		Part B: Dose Expansion Phase - Arm 7		Part B: Dose Expansion Phase - Arm 8
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		11/12 (91.7%)		5/6 (83.3%)		12/13 (92.3%)		6/6 (100%)		21/23 (91.3%)		22/23 (95.7%)		16/19 (84.2%)		13/20 (65%)		15/23 (65.2%)		17/20 (85%)		14/21 (66.7%)		18/21 (85.7%)		5/10 (50%)
Blood and lymphatic system disorders
Anaemia	2/12 (16.7%)		2/12 (16.7%)		2/6 (33.3%)		4/13 (30.8%)		3/6 (50%)		5/23 (21.7%)		2/23 (8.7%)		10/19 (52.6%)		5/20 (25%)		3/23 (13%)		2/20 (10%)		5/21 (23.8%)		5/21 (23.8%)		2/10 (20%)
Lymphopenia	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Neutropenia	2/12 (16.7%)		0/12 (0%)		1/6 (16.7%)		1/13 (7.7%)		1/6 (16.7%)		1/23 (4.3%)		1/23 (4.3%)		2/19 (10.5%)		1/20 (5%)		0/23 (0%)		1/20 (5%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Thrombocytopenia	0/12 (0%)		0/12 (0%)		3/6 (50%)		0/13 (0%)		2/6 (33.3%)		3/23 (13%)		1/23 (4.3%)		2/19 (10.5%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Endocrine disorders
Hyperthyroidism	1/12 (8.3%)		0/12 (0%)		1/6 (16.7%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hypothyroidism	1/12 (8.3%)		1/12 (8.3%)		1/6 (16.7%)		1/13 (7.7%)		2/6 (33.3%)		4/23 (17.4%)		0/23 (0%)		2/19 (10.5%)		0/20 (0%)		2/23 (8.7%)		1/20 (5%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Eye disorders
Dry eye	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		3/19 (15.8%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Vision blurred	0/12 (0%)		0/12 (0%)		0/6 (0%)		2/13 (15.4%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		1/23 (4.3%)		2/23 (8.7%)		2/19 (10.5%)		0/20 (0%)		1/23 (4.3%)		1/20 (5%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Abdominal distension	1/12 (8.3%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		2/23 (8.7%)		1/19 (5.3%)		0/20 (0%)		2/23 (8.7%)		1/20 (5%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Abdominal pain	2/12 (16.7%)		1/12 (8.3%)		2/6 (33.3%)		1/13 (7.7%)		1/6 (16.7%)		3/23 (13%)		5/23 (21.7%)		3/19 (15.8%)		1/20 (5%)		0/23 (0%)		4/20 (20%)		1/21 (4.8%)		1/21 (4.8%)		1/10 (10%)
Abdominal pain lower	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Abdominal pain upper	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		1/23 (4.3%)		2/20 (10%)		0/21 (0%)		2/21 (9.5%)		1/10 (10%)
Ascites	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Constipation	4/12 (33.3%)		3/12 (25%)		1/6 (16.7%)		1/13 (7.7%)		1/6 (16.7%)		4/23 (17.4%)		8/23 (34.8%)		5/19 (26.3%)		6/20 (30%)		3/23 (13%)		8/20 (40%)		3/21 (14.3%)		5/21 (23.8%)		0/10 (0%)
Diarrhoea	1/12 (8.3%)		6/12 (50%)		4/6 (66.7%)		5/13 (38.5%)		3/6 (50%)		10/23 (43.5%)		6/23 (26.1%)		8/19 (42.1%)		4/20 (20%)		4/23 (17.4%)		6/20 (30%)		6/21 (28.6%)		3/21 (14.3%)		1/10 (10%)
Dry mouth	2/12 (16.7%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Dyspepsia	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		1/23 (4.3%)		2/23 (8.7%)		2/19 (10.5%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Gastrooesophageal reflux disease	1/12 (8.3%)		3/12 (25%)		1/6 (16.7%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		2/23 (8.7%)		0/19 (0%)		1/20 (5%)		1/23 (4.3%)		4/20 (20%)		2/21 (9.5%)		0/21 (0%)		2/10 (20%)
Nausea	5/12 (41.7%)		10/12 (83.3%)		4/6 (66.7%)		10/13 (76.9%)		5/6 (83.3%)		18/23 (78.3%)		17/23 (73.9%)		15/19 (78.9%)		8/20 (40%)		8/23 (34.8%)		7/20 (35%)		12/21 (57.1%)		12/21 (57.1%)		3/10 (30%)
Oesophagitis	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Rectal haemorrhage	1/12 (8.3%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Toothache	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Vomiting	1/12 (8.3%)		7/12 (58.3%)		1/6 (16.7%)		5/13 (38.5%)		3/6 (50%)		6/23 (26.1%)		5/23 (21.7%)		8/19 (42.1%)		3/20 (15%)		2/23 (8.7%)		4/20 (20%)		4/21 (19%)		3/21 (14.3%)		2/10 (20%)
Dysphagia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		4/20 (20%)		1/21 (4.8%)		1/21 (4.8%)		0/10 (0%)
General disorders
Chills	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Fatigue	7/12 (58.3%)		7/12 (58.3%)		3/6 (50%)		7/13 (53.8%)		4/6 (66.7%)		10/23 (43.5%)		15/23 (65.2%)		12/19 (63.2%)		12/20 (60%)		5/23 (21.7%)		11/20 (55%)		9/21 (42.9%)		9/21 (42.9%)		5/10 (50%)
Influenza like illness	2/12 (16.7%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pyrexia	4/12 (33.3%)		2/12 (16.7%)		2/6 (33.3%)		0/13 (0%)		1/6 (16.7%)		3/23 (13%)		1/23 (4.3%)		2/19 (10.5%)		1/20 (5%)		0/23 (0%)		2/20 (10%)		2/21 (9.5%)		1/21 (4.8%)		0/10 (0%)
Asthenia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		2/23 (8.7%)		4/19 (21.1%)		0/20 (0%)		3/23 (13%)		1/20 (5%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Non-cardiac chest pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		2/23 (8.7%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		1/20 (5%)		1/21 (4.8%)		1/21 (4.8%)		0/10 (0%)
Oedema peripheral	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		3/23 (13%)		5/23 (21.7%)		1/19 (5.3%)		2/20 (10%)		1/23 (4.3%)		0/20 (0%)		3/21 (14.3%)		6/21 (28.6%)		3/10 (30%)
Hepatobiliary disorders
Autoimmune hepatitis	1/12 (8.3%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hepatitis	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		3/23 (13%)		1/23 (4.3%)		1/19 (5.3%)		0/20 (0%)		3/23 (13%)		0/20 (0%)		3/21 (14.3%)		0/21 (0%)		0/10 (0%)
Infections and infestations
Lower respiratory tract infection bacterial	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Nasopharyngitis	2/12 (16.7%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Oral candidiasis	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		2/13 (15.4%)		1/6 (16.7%)		1/23 (4.3%)		2/23 (8.7%)		1/19 (5.3%)		2/20 (10%)		1/23 (4.3%)		1/20 (5%)		2/21 (9.5%)		1/21 (4.8%)		0/10 (0%)
Rhinitis	0/12 (0%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Upper respiratory tract infection	3/12 (25%)		3/12 (25%)		2/6 (33.3%)		2/13 (15.4%)		1/6 (16.7%)		5/23 (21.7%)		1/23 (4.3%)		7/19 (36.8%)		3/20 (15%)		2/23 (8.7%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		1/10 (10%)
Urinary tract infection	0/12 (0%)		2/12 (16.7%)		2/6 (33.3%)		3/13 (23.1%)		2/6 (33.3%)		4/23 (17.4%)		3/23 (13%)		1/19 (5.3%)		3/20 (15%)		1/23 (4.3%)		3/20 (15%)		4/21 (19%)		0/21 (0%)		1/10 (10%)
Vulvovaginal candidiasis	0/9 (0%)		1/11 (9.1%)		2/5 (40%)		0/12 (0%)		0/5 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/0 (NaN)		0/10 (0%)		0/3 (0%)		0/6 (0%)		0/9 (0%)		0/5 (0%)
Bronchitis	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		2/19 (10.5%)		3/20 (15%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Lower respiratory tract infection	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		1/19 (5.3%)		1/20 (5%)		2/23 (8.7%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Injury, poisoning and procedural complications
Fall	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Investigations
Alanine aminotransferase increased	1/12 (8.3%)		2/12 (16.7%)		3/6 (50%)		3/13 (23.1%)		3/6 (50%)		4/23 (17.4%)		3/23 (13%)		3/19 (15.8%)		3/20 (15%)		2/23 (8.7%)		2/20 (10%)		8/21 (38.1%)		1/21 (4.8%)		2/10 (20%)
Aspartate aminotransferase increased	1/12 (8.3%)		2/12 (16.7%)		3/6 (50%)		3/13 (23.1%)		1/6 (16.7%)		3/23 (13%)		3/23 (13%)		3/19 (15.8%)		3/20 (15%)		2/23 (8.7%)		2/20 (10%)		9/21 (42.9%)		2/21 (9.5%)		2/10 (20%)
Blood alkaline phosphatase increased	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Blood bilirubin increased	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		1/23 (4.3%)		3/19 (15.8%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		1/21 (4.8%)		1/21 (4.8%)		1/10 (10%)
Gamma-glutamyltransferase increased	0/12 (0%)		2/12 (16.7%)		2/6 (33.3%)		0/13 (0%)		1/6 (16.7%)		1/23 (4.3%)		1/23 (4.3%)		1/19 (5.3%)		0/20 (0%)		2/23 (8.7%)		0/20 (0%)		2/21 (9.5%)		0/21 (0%)		0/10 (0%)
Weight decreased	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		1/6 (16.7%)		0/23 (0%)		2/23 (8.7%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		2/20 (10%)		3/21 (14.3%)		3/21 (14.3%)		0/10 (0%)
Blood creatine phosphokinase increased	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		3/23 (13%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		3/20 (15%)		2/21 (9.5%)		0/21 (0%)		0/10 (0%)
Blood creatinine increased	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		2/23 (8.7%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		1/23 (4.3%)		1/20 (5%)		2/21 (9.5%)		0/21 (0%)		0/10 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/12 (0%)		2/12 (16.7%)		0/6 (0%)		2/13 (15.4%)		0/6 (0%)		6/23 (26.1%)		4/23 (17.4%)		2/19 (10.5%)		2/20 (10%)		8/23 (34.8%)		3/20 (15%)		3/21 (14.3%)		5/21 (23.8%)		2/10 (20%)
Dehydration	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		1/20 (5%)		2/23 (8.7%)		3/20 (15%)		1/21 (4.8%)		2/21 (9.5%)		0/10 (0%)
Hypercalcaemia	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hypokalaemia	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		2/13 (15.4%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		4/19 (21.1%)		0/20 (0%)		0/23 (0%)		2/20 (10%)		2/21 (9.5%)		2/21 (9.5%)		1/10 (10%)
Hypophosphataemia	1/12 (8.3%)		2/12 (16.7%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)		2/12 (16.7%)		1/6 (16.7%)		2/13 (15.4%)		1/6 (16.7%)		5/23 (21.7%)		3/23 (13%)		3/19 (15.8%)		5/20 (25%)		1/23 (4.3%)		1/20 (5%)		1/21 (4.8%)		2/21 (9.5%)		2/10 (20%)
Back pain	1/12 (8.3%)		3/12 (25%)		3/6 (50%)		0/13 (0%)		3/6 (50%)		8/23 (34.8%)		3/23 (13%)		5/19 (26.3%)		5/20 (25%)		5/23 (21.7%)		4/20 (20%)		3/21 (14.3%)		3/21 (14.3%)		0/10 (0%)
Flank pain	0/12 (0%)		2/12 (16.7%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Groin pain	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Muscle spasms	1/12 (8.3%)		0/12 (0%)		1/6 (16.7%)		2/13 (15.4%)		0/6 (0%)		3/23 (13%)		6/23 (26.1%)		4/19 (21.1%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Muscular weakness	0/12 (0%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Musculoskeletal chest pain	0/12 (0%)		0/12 (0%)		2/6 (33.3%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		3/19 (15.8%)		3/20 (15%)		2/23 (8.7%)		2/20 (10%)		0/21 (0%)		0/21 (0%)		1/10 (10%)
Myalgia	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		1/6 (16.7%)		5/23 (21.7%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		1/21 (4.8%)		1/21 (4.8%)		0/10 (0%)
Neck pain	0/12 (0%)		2/12 (16.7%)		1/6 (16.7%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pain in extremity	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		3/13 (23.1%)		1/6 (16.7%)		1/23 (4.3%)		0/23 (0%)		3/19 (15.8%)		3/20 (15%)		0/23 (0%)		1/20 (5%)		1/21 (4.8%)		0/21 (0%)		1/10 (10%)
Musculoskeletal pain	1/12 (8.3%)		1/12 (8.3%)		2/6 (33.3%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		1/23 (4.3%)		0/19 (0%)		2/20 (10%)		0/23 (0%)		1/20 (5%)		2/21 (9.5%)		1/21 (4.8%)		0/10 (0%)
Nervous system disorders
Dizziness	1/12 (8.3%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		2/23 (8.7%)		2/23 (8.7%)		2/19 (10.5%)		0/20 (0%)		1/23 (4.3%)		3/20 (15%)		2/21 (9.5%)		4/21 (19%)		0/10 (0%)
Dysgeusia	1/12 (8.3%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		2/6 (33.3%)		0/23 (0%)		1/23 (4.3%)		2/19 (10.5%)		2/20 (10%)		2/23 (8.7%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		0/10 (0%)
Headache	3/12 (25%)		3/12 (25%)		2/6 (33.3%)		2/13 (15.4%)		1/6 (16.7%)		5/23 (21.7%)		3/23 (13%)		5/19 (26.3%)		3/20 (15%)		3/23 (13%)		3/20 (15%)		2/21 (9.5%)		2/21 (9.5%)		0/10 (0%)
Paraesthesia	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		0/23 (0%)		3/19 (15.8%)		2/20 (10%)		1/23 (4.3%)		2/20 (10%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Peripheral sensory neuropathy	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		1/23 (4.3%)		1/19 (5.3%)		0/20 (0%)		1/23 (4.3%)		0/20 (0%)		1/21 (4.8%)		1/21 (4.8%)		0/10 (0%)
Psychiatric disorders
Anxiety	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		2/23 (8.7%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		1/20 (5%)		2/21 (9.5%)		3/21 (14.3%)		1/10 (10%)
Insomnia	1/12 (8.3%)		0/12 (0%)		1/6 (16.7%)		0/13 (0%)		1/6 (16.7%)		1/23 (4.3%)		2/23 (8.7%)		1/19 (5.3%)		5/20 (25%)		0/23 (0%)		2/20 (10%)		1/21 (4.8%)		1/21 (4.8%)		1/10 (10%)
Depression	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		0/23 (0%)		0/19 (0%)		1/20 (5%)		1/23 (4.3%)		2/20 (10%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Renal and urinary disorders
Dysuria	1/12 (8.3%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/9 (11.1%)		0/11 (0%)		0/5 (0%)		1/12 (8.3%)		0/5 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/0 (NaN)		0/10 (0%)		0/3 (0%)		0/6 (0%)		0/9 (0%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	4/12 (33.3%)		2/12 (16.7%)		2/6 (33.3%)		1/13 (7.7%)		1/6 (16.7%)		1/23 (4.3%)		3/23 (13%)		5/19 (26.3%)		3/20 (15%)		6/23 (26.1%)		2/20 (10%)		1/21 (4.8%)		3/21 (14.3%)		1/10 (10%)
Dyspnoea	1/12 (8.3%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		1/6 (16.7%)		2/23 (8.7%)		2/23 (8.7%)		3/19 (15.8%)		2/20 (10%)		4/23 (17.4%)		0/20 (0%)		3/21 (14.3%)		3/21 (14.3%)		1/10 (10%)
Epistaxis	0/12 (0%)		0/12 (0%)		0/6 (0%)		2/13 (15.4%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Oropharyngeal pain	2/12 (16.7%)		0/12 (0%)		1/6 (16.7%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Productive cough	0/12 (0%)		1/12 (8.3%)		1/6 (16.7%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pulmonary embolism	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		1/23 (4.3%)		1/23 (4.3%)		1/19 (5.3%)		0/20 (0%)		0/23 (0%)		1/20 (5%)		0/21 (0%)		2/21 (9.5%)		0/10 (0%)
Rhinorrhoea	0/12 (0%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pleural effusion	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		0/23 (0%)		1/19 (5.3%)		0/20 (0%)		1/23 (4.3%)		1/20 (5%)		1/21 (4.8%)		3/21 (14.3%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/12 (0%)		0/12 (0%)		1/6 (16.7%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Dry skin	1/12 (8.3%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Pruritus	1/12 (8.3%)		1/12 (8.3%)		1/6 (16.7%)		2/13 (15.4%)		0/6 (0%)		3/23 (13%)		1/23 (4.3%)		1/19 (5.3%)		1/20 (5%)		5/23 (21.7%)		0/20 (0%)		1/21 (4.8%)		1/21 (4.8%)		0/10 (0%)
Rash	1/12 (8.3%)		0/12 (0%)		1/6 (16.7%)		1/13 (7.7%)		1/6 (16.7%)		3/23 (13%)		0/23 (0%)		4/19 (21.1%)		1/20 (5%)		1/23 (4.3%)		1/20 (5%)		0/21 (0%)		2/21 (9.5%)		0/10 (0%)
Rash macular	1/12 (8.3%)		1/12 (8.3%)		0/6 (0%)		0/13 (0%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Rash maculo-papular	0/12 (0%)		2/12 (16.7%)		1/6 (16.7%)		1/13 (7.7%)		1/6 (16.7%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Vascular disorders
Deep vein thrombosis	1/12 (8.3%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		0/23 (0%)		0/23 (0%)		0/19 (0%)		0/20 (0%)		0/23 (0%)		0/20 (0%)		0/21 (0%)		0/21 (0%)		0/10 (0%)
Hot flush	2/12 (16.7%)		0/12 (0%)		0/6 (0%)		1/13 (7.7%)		0/6 (0%)		2/23 (8.7%)		2/23 (8.7%)		0/19 (0%)		1/20 (5%)		0/23 (0%)		0/20 (0%)		1/21 (4.8%)		0/21 (0%)		0/10 (0%)
Hypertension	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		0/23 (0%)		0/19 (0%)		2/20 (10%)		1/23 (4.3%)		0/20 (0%)		0/21 (0%)		1/21 (4.8%)		1/10 (10%)
Hypotension	0/12 (0%)		0/12 (0%)		0/6 (0%)		0/13 (0%)		0/6 (0%)		1/23 (4.3%)		2/23 (8.7%)		1/19 (5.3%)		0/20 (0%)		1/23 (4.3%)		3/20 (15%)		2/21 (9.5%)		0/21 (0%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.