Zanubrutinib (BGB-3111) in Combination With Tislelizumab (BGB-A317) in Participants With B-cell Malignancies
Study Details
Study Description
Brief Summary
This study is evaluating the safety and preliminary efficacy of BGB-3111 in combination with BGB-A317 in participants with B-cell lymphoid malignancies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Zanubrutinib abd Tislelizumab Based on results of the dose escalation cohorts and the identified recommended Phase 2 dose, all patients will receive zanubrutinib at 160 mg orally twice daily in combination with intravenous infusion of tislelizumab 200mg given every 21 days, to be continued until disease progression, unacceptable toxicity, treatment consent withdrawal, or study termination |
Drug: Zanubrutinib
Other Names:
Drug: Tislelizumab
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Dose Escalation: Maximum Tolerated Dose (MTD) of Tislelizumab [From the date of first dose of study drugs until RP2D was determined (Approximately 1 year and 10 months)]
The MTD of tislelizumab is considered the dose level below that at which at least 2 participants (or at least 33%) experience a dose-limiting toxicity (DLT).
- Dose Escalation: RP2D of Tislelizumab [From the date of first dose of study drugs until final R2PD was decided (Approximately 1 year and 10 months)]
The RP2D of tislelizumab in combination with zanubrutinib will be selected by taking into account the safety, tolerability, and pharmacokinetic (PK) profile.
Secondary Outcome Measures
- Number of Participants With TEAEs and SAEs [From the day of first dose of study drug until end of study (up to 4 years and 6 months)]
A treatment-emergent adverse event (TEAE) was defined as an AE that had an onset date during the treatment emergent period, defined as from the first dose date of zanubrutinib or tislelizumab (whichever is earlier) through 30 days after the last dose (permanent discontinuation of study drug) of zanubrutinib or 90 days after the last dose of tislelizumab, whichever is later, or prior to initiation of new anti-cancer therapy. Treatment-related serious adverse events (SAEs) and any worsening of a TEAE by PT post treatment-emergent period were also counted as TEAEs.
- Overall Response Rate [Up to 4 years and 6 months]
ORR, is defined as the percentage of participants who had complete response (CR) or partial response (PR) by standard disease-specific response criteria. for WM participants ORR includes minor response (MR) and very good partial response (VGPR).
- Duration of Response (DOR) [Up to 4 years and 6 months]
DOR is defined as the time from the date that a confirmed objective response is first documented to the date of progressive disease (PD) or death due to any cause for those participants with a confirmed PR or CR.
- Progression Free Survival (PFS) [Up to 4 years and 6 months]
PFS, is defined as the time from the first dose of study medication to objective disease progression or death
- Number of Participants With Anti-Drug Antibodies (ADAs) to Tislelizumab [From the day of first dose of study drug until end of study (up to 4 years and 6 months)]
Eligibility Criteria
Criteria
Key Inclusion Criteria
Participants may be entered in the study only if they meet all of the following criteria:
-
Dose escalation for Dose Levels 1, 2, and 3: participants with relapsed or refractory World Health Organization (WHO) classification-defined B-lymphoid malignancy following at least 1 line of therapy, with no therapy of higher priority available, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), human cultured lymphoblast (HCL), Marginal zone lymphoma (MZL), non-germinal center B-cell (GCB) DLBCL, GCB DLBCL, transformed FL, and Richter's transformation (NOTE: participants with WM are excluded from enrollment as of Amendment 3).
-
Dose expansion for Cohorts 1 to 4: participants with either of the following relapsed or refractory WHO-classified lymphoid malignancies who have received at least 1 prior line of standard therapy: a. Cohort 1: GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling. b. Cohort 2: non-GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling. participants who have transformed to DLBCL from another histology may be enrolled into Cohort 3. c. Cohort 3: Transformed lymphoid malignancy, including but not limited to: i. Large cell transformation of chronic lymphocytic leukemia (Richter's transformation). ii. Large cell transformation of other WHO-classified indolent non-Hodgkin's lymphoma, including FL, or MZL. d. Cohort 4: Histologically confirmed primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL) of breast or testicular origin: i. Must be able to tolerate lumbar puncture and/or Ommaya taps. ii. Must have received at least 1 prior central nervous system (CNS)-directed therapy. iii. Presence of brain parenchymal and/or leptomeningeal disease.
-
Aged ≥ 18 years, able and willing to provide written informed consent and to comply with the study protocol.
-
Measurable disease for non-Hodgkin lymphoma defined as ≥ 1 nodal lesion that is > 15 mm in the longest diameter and can be accurately measured in at least 2 dimensions with computed tomography (CT) scan, or ≥ 1 extra-nodal lesion that is > 10 mm in the longest diameter and can be accurately measured in at least 2 dimensions with CT scan, except for PCNSL or SCNSL.
-
Participants with an accessible tumor lesion must agree to a tumor biopsy at screening and another before the drug administration on Cycle 1 Day 8, ideally taken from the same tumor lesion, for biomarker analysis (up to first 12 qualified participants), except for PCNSL. Additionally, participants with DLBCL must have archival tumor tissue or agree to a tumor biopsy for confirmation of the DLBCL subtype.
-
Laboratory parameters as specified below: a. Hematologic: Platelet count ≥ 50 × 109/L; absolute neutrophil count ≥ 1.0 × 109 cells/L; participants with neutrophils < 1.0 × 109/L unless cytopenias are a direct result of active leukemia or lymphoma, in which case platelet count ≥ 35 × 109/L, absolute neutrophil count ≥ 0.75 × 109/L are allowed. (Note: Platelet transfusion administered ≤ 7 days of screening to raise pre-treatment platelet count to ≥ 35 x 109/L is prohibited.) b. Hepatic: Total bilirubin ≤ 1.5 the upper limit of normal (ULN) or ≤ 2.0 × ULN for participants with Gilbert syndrome, aspartate transaminase (AST), and alanine aminotransaminase (ALT) ≤ 3 × ULN. c. Renal: Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection). participants requiring hemodialysis will be excluded.
-
Anticipated survival of at least 4 months.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
-
Female participants of childbearing potential and nonsterile males must practice at least 1 of the following methods of birth control with partner(s) throughout the study and for ≥ 3 months after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, intrauterine device or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.
-
Male participants must not donate sperm from initial study drug administration until 180 days after drug discontinuation.
Key Exclusion Criteria
Participants will not be entered in the study for any of the following reasons:
-
Known, active, CNS lymphoma or leukemia, except for Cohorts 4.
-
Diagnosis with Waldenstrom's macroglobulinemia (WM).
-
For PCNSL and SCNSL (Cohorts 4): a. Require corticosteroid therapy > 16 mg dexamethasone daily or equivalent. b. Corticosteroid therapy ≤ 16 mg dexamethasone daily or equivalent at study entry from which, in the Investigator's opinion, it is expected that the participant cannot be tapered off after the first 4 weeks of study treatment. c. Intraocular PCNSL without evidence of brain disease. d. SCNSL actively receiving treatment for extra-CNS disease. e. PCNSL actively receiving concomitant local or systemic therapy for CNS disease.
-
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
-
History of stroke or cerebral hemorrhage within 6 months of enrollment.
-
History of significant cardiovascular disease, defined as: a. Congestive heart failure greater than New York Heart Association (NYHA) class II according to the NYHA functional classification. b. Unstable angina or myocardial infarction with 6 months of enrollment. c. Serious cardiac arrhythmia or clinically significant ECG abnormality: corrected QT wave (QTcF) > 480 msec based on the Fridericia's formula or other ECG abnormalities including second-degree atrioventricular block type II, third-degree atrioventricular block. Participants who have a pacemaker will be allowed on study despite ECG abnormalities or the inability to calculate the QTc.
-
Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, congestive obstructive pulmonary disease).
-
History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.
-
Prior Bruton's tyrosine kinase (BTK) inhibitor or anti-PD-1/anti-PD-L1 treatment.
-
Any illness or condition that in the opinion of the investigator may affect safety of treatment or evaluation of any study endpoint.
-
Active autoimmune diseases or history of severe autoimmune diseases; these include but are not limited to a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis systemic lupus erythematosus, rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, or clinically manifest antiphospholipid syndrome. Note: Participants are permitted to enroll if they have vitiligo, eczema, type I diabetes mellitus, or endocrine deficiencies, including thyroiditis managed with replacement hormones including physiologic doses of corticosteroids. Participants with Sjögren's syndrome and psoriasis controlled with topical medication and participants with positive serology, such as antinuclear antibodies or antithyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
-
A condition requiring systemic treatment with either corticosteroids (> 20 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, except for PCNSL and SCNSL. Note: adrenal replacement doses ≤ 20 mg daily prednisone or equivalents are permitted in the absence of active autoimmune disease; Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
-
History of interstitial lung disease or noninfectious pneumonitis, except for those induced by radiation therapy.
-
Requirement for medications which strong cytochrome P450 (CYP)3A inhibitors or inducers.
-
Vaccination with a live vaccine within 28 days of the initiation of treatment.
-
A candidate for hematopoietic stem cell transplantation. Participants are excluded if they had received an allogeneic stem cell transplantation within 6 months or have active graft-versus-host-disease requiring ongoing immunosuppression.
-
Participated in any investigational drug study within 28 days or not recovered from toxicity of any prior chemotherapy to Grade ≤ 1.
-
History of other active malignancies within 2 years of study entry, with the exception of adequately treated in-situ carcinoma of cervix; localized basal cell or squamous cell carcinoma of skin; or previous malignancy confined and treated locally (surgery or other modality) with curative intent.
-
Major surgery in the past 4 weeks prior to the first day of screening.
-
Active and symptomatic fungal, bacterial, and/or viral infection; human T-cell lymphotropic virus type 1 seropositive status.
-
Human immunodeficiency virus (HIV) infection, or active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] detected. • Hepatitis B/C serologic markers and viral load will be tested at screening. The hepatitis B testing includes HBsAg, HBcAb, and HBsAb as well as hepatitis B virus (HBV) DNA by Polymerase chain reaction (PCR) if the participant is negative for HBsAg but HBcAb positive (regardless of HBsAb status). The hepatitis C testing includes Hepatitis C virus (HCV) antibody as well as HCV RNA by PCR if the Participant is HCV antibody positive. Participants with positive HBsAg and/or detectable level of HBV DNA or detectable level of HCV RNA (≥ 15 IU/mL) are not eligible. Participants negative for HBsAg, HBcAb positive, and HBV DNA negative must undergo monthly HBV DNA screening by PCR. Participants positive for HCV antibody but negative for HCV RNA (defined as < 15 IU) must undergo monthly HCV RNA screening.
-
Inability to comply with study procedures.
-
Pregnant or nursing women.
-
Men or women of childbearing potential who refuse to use an adequate measure of contraception, unless they have past medical history of surgical sterilization.
-
Currently taking or plan to take CNS penetrant therapy such as thiotepa, cytarabine, or partially CNS penetrant agents known to be active in lymphoid tumors, such as rituximab.
-
Has taken or plans to take any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin), or any investigational therapies to treat leukemia or lymphoma within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration, including CNS penetrating agents.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St Vincent's Hospital | Darlinghurst | New South Wales | Australia | |
| 2 | Concord Hospital | Sydney | New South Wales | Australia | 2139 |
| 3 | Royal Hobart Hospital | Hobart | Tasmania | Australia | |
| 4 | Monash Hospital | Clayton | Victoria | Australia | 3168 |
| 5 | Peter MacCallum Cancer Centre | Melbourne | Victoria | Australia | 3002 |
| 6 | Epworth Healthcare | Richmond | Victoria | Australia | |
| 7 | Sir Charles Gairdner Hospital | Nedlands | Western Australia | Australia | 6009 |
| 8 | Guangdong General Hospital | Guangzhou | Guangdong | China | |
| 9 | Harbin Medical University Cancer Hospital | Harbin | Heilongjiang | China | 150081 |
| 10 | Shanghai jiaotong university school of medicine Ruijin Hospital | Shanghai | Shanghai | China | 200025 |
Sponsors and Collaborators
- BeiGene
Investigators
- Principal Investigator: Study Director, BeiGene
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- BGB-3111_BGB-A317_Study_001
Study Results
Participant Flow
| Recruitment Details | The study consisted of a dose escalation phase during which 3 dose levels of tislelizumab were administered in combination with a total of 320 mg zanubrutinib to determine the recommended phase 2 dose (RP2D). Once RP2D was determined all participants remaining in the study were switched to RP2D. A total of 75 participants were enrolled in both phases combined. As pre-specified in the protocol, analyses were conducted by disease subtype on the overall enrolled participants and not by phases. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W |
|---|---|---|---|---|
| Arm/Group Description | Zanubrutinib 320 mg once daily (QD) orally with tislelizumab 2.0 milligrams/kilogram (mg/kg) intravenously (IV) once every 3 weeks until unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor. | Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 160 mg twice daily (BID) orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor |
| Period Title: Overall Study | ||||
| STARTED | 15 | 10 | 7 | 43 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 15 | 10 | 7 | 43 |
Baseline Characteristics
| Arm/Group Title | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Zanubrutinib 320 mg QD orally with tislelizumab 2.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Total of all reporting groups |
| Overall Participants | 15 | 10 | 7 | 43 | 75 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
60.4
(12.63)
|
60.7
(6.52)
|
70.4
(5.26)
|
66.7
(9.85)
|
65.0
(10.20)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
4
26.7%
|
5
50%
|
4
57.1%
|
16
37.2%
|
29
38.7%
|
| Male |
11
73.3%
|
5
50%
|
3
42.9%
|
27
62.8%
|
46
61.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
1
1.3%
|
| Not Hispanic or Latino |
12
80%
|
7
70%
|
7
100%
|
38
88.4%
|
64
85.3%
|
| Unknown or Not Reported |
3
20%
|
3
30%
|
0
0%
|
4
9.3%
|
10
13.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Race- White |
14
93.3%
|
9
90%
|
7
100%
|
33
76.7%
|
63
84%
|
| Race - Asian |
1
6.7%
|
1
10%
|
0
0%
|
9
20.9%
|
11
14.7%
|
| Race - Other |
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
1
1.3%
|
Outcome Measures
| Title | Dose Escalation: Maximum Tolerated Dose (MTD) of Tislelizumab |
|---|---|
| Description | The MTD of tislelizumab is considered the dose level below that at which at least 2 participants (or at least 33%) experience a dose-limiting toxicity (DLT). |
| Time Frame | From the date of first dose of study drugs until RP2D was determined (Approximately 1 year and 10 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Dose Escalation Phase: Safety analysis set: Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab. |
| Arm/Group Title | Dose Escalation Phase |
|---|---|
| Arm/Group Description | Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor |
| Measure Participants | 32 |
| Number [mg] |
NA
|
| Title | Dose Escalation: RP2D of Tislelizumab |
|---|---|
| Description | The RP2D of tislelizumab in combination with zanubrutinib will be selected by taking into account the safety, tolerability, and pharmacokinetic (PK) profile. |
| Time Frame | From the date of first dose of study drugs until final R2PD was decided (Approximately 1 year and 10 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Dose Escalation Phase: Safety analysis set: Included all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab. |
| Arm/Group Title | Dose Escalation Phase |
|---|---|
| Arm/Group Description | Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor |
| Measure Participants | 32 |
| Number [mg] |
200
|
| Title | Number of Participants With TEAEs and SAEs |
|---|---|
| Description | A treatment-emergent adverse event (TEAE) was defined as an AE that had an onset date during the treatment emergent period, defined as from the first dose date of zanubrutinib or tislelizumab (whichever is earlier) through 30 days after the last dose (permanent discontinuation of study drug) of zanubrutinib or 90 days after the last dose of tislelizumab, whichever is later, or prior to initiation of new anti-cancer therapy. Treatment-related serious adverse events (SAEs) and any worsening of a TEAE by PT post treatment-emergent period were also counted as TEAEs. |
| Time Frame | From the day of first dose of study drug until end of study (up to 4 years and 6 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W |
|---|---|---|---|---|
| Arm/Group Description | Zanubrutinib 320 mg QD orally with tislelizumab 2.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor |
| Measure Participants | 15 | 10 | 7 | 43 |
| Participants With at Least One TEAE |
15
100%
|
9
90%
|
7
100%
|
40
93%
|
| Participants With at Least One SAE |
10
66.7%
|
10
100%
|
4
57.1%
|
23
53.5%
|
| Title | Overall Response Rate |
|---|---|
| Description | ORR, is defined as the percentage of participants who had complete response (CR) or partial response (PR) by standard disease-specific response criteria. for WM participants ORR includes minor response (MR) and very good partial response (VGPR). |
| Time Frame | Up to 4 years and 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set : Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab. Per protocol Safety analysis set was used for all safety and efficacy outcome analyses. All efficacy analyses were done by disease type for both part 1 and part 2 combined and not by dose level as specified in the protocol. |
| Arm/Group Title | Other B-Cell Malignancies | GCB DLBCL | Non-GCB DLBCL | Richter's Transformation | Transformed Lymphoid Malignancy | PCNSL or SCNSL of Breast or Testicular Origin |
|---|---|---|---|---|---|---|
| Arm/Group Description | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. This group included participants with CLL/SLL, WM, FL, MCL and MZL. | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor |
| Measure Participants | 16 | 12 | 15 | 7 | 20 | 5 |
| Number (95% Confidence Interval) [Percentage of participants] |
37.5
250%
|
25.0
250%
|
40.0
571.4%
|
42.9
99.8%
|
40
53.3%
|
40
NaN
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR is defined as the time from the date that a confirmed objective response is first documented to the date of progressive disease (PD) or death due to any cause for those participants with a confirmed PR or CR. |
| Time Frame | Up to 4 years and 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set : Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab. Per protocol Safety analysis set was used for all safety and efficacy outcome analyses. All efficacy analyses were done by disease type for both part 1 and part 2 combined and not by dose level as specified in the protocol. |
| Arm/Group Title | Other B-Cell Malignancies | GCB DLBCL | Non-GCB DLBCL | Richter's Transformation | Transformed Lymphoid Malignancy | PCNSL or SCNSL of Breast or Testicular Origin |
|---|---|---|---|---|---|---|
| Arm/Group Description | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. This group included participants with CLL/SLL, WM, FL, MCL and MZL. | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor |
| Measure Participants | 16 | 12 | 15 | 7 | 20 | 5 |
| Median (95% Confidence Interval) [Months] |
22.36
|
NA
|
6.79
|
17.47
|
8.89
|
7.80
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS, is defined as the time from the first dose of study medication to objective disease progression or death |
| Time Frame | Up to 4 years and 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set : Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab. Per protocol Safety analysis set was used for all safety and efficacy outcome analyses. All efficacy analyses were done by disease type for both part 1 and part 2 combined and not by dose level as specified in the protocol. |
| Arm/Group Title | Other B-Cell Malignancies | GCB DLBCL | Non-GCB DLBCL | Richter's Transformation | Transformed Lymphoid Malignancy | PCNSL or SCNSL of Breast or Testicular Origin |
|---|---|---|---|---|---|---|
| Arm/Group Description | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. This group included participants with CLL/SLL, WM, FL, MCL and MZL. | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor |
| Measure Participants | 16 | 12 | 15 | 7 | 20 | 5 |
| Median (95% Confidence Interval) [Months] |
16.94
|
1.43
|
2.80
|
2.93
|
4.68
|
8.42
|
| Title | Number of Participants With Anti-Drug Antibodies (ADAs) to Tislelizumab |
|---|---|
| Description | |
| Time Frame | From the day of first dose of study drug until end of study (up to 4 years and 6 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of tislelizumab. N is the number of evaluable participants. Evaluable participants received at least one complete dose of Tislelizumab and for whom one baseline ADA and at least one post dose ADA values are available. |
| Arm/Group Title | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W |
|---|---|---|---|---|
| Arm/Group Description | Zanubrutinib 320 mg QD orally with tislelizumab 2.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor |
| Measure Participants | 3 | 4 | 5 | 35 |
| Treatment Emergent ADA |
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
| Neutralizing antibody Positive |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | From the Day of first dose of study drug until end of Study (up to 4 years and 6 months) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety analysis set: Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab | |||||||
| Arm/Group Title | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | ||||
| Arm/Group Description | Zanubrutinib 320 mg QD orally with tislelizumab 2.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor. | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor | ||||
All Cause Mortality |
||||||||
| Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/15 (33.3%) | 4/10 (40%) | 4/7 (57.1%) | 21/43 (48.8%) | ||||
Serious Adverse Events |
||||||||
| Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/15 (66.7%) | 10/10 (100%) | 4/7 (57.1%) | 23/43 (53.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Atypical haemolytic uraemic syndrome | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Febrile neutropenia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 3 |
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Atrial flutter | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Eye disorders | ||||||||
| Ulcerative keratitis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Ascites | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Colitis microscopic | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Constipation | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Diarrhoea | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Immune-mediated enterocolitis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 1/43 (2.3%) | 2 |
| Melaena | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Nausea | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Vomiting | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| General disorders | ||||||||
| Catheter site haemorrhage | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Multiple organ dysfunction syndrome | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Pyrexia | 0/15 (0%) | 0 | 2/10 (20%) | 4 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Immune-mediated hepatitis | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Immune system disorders | ||||||||
| Drug hypersensitivity | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 2 | 0/43 (0%) | 0 |
| Infections and infestations | ||||||||
| Abscess limb | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Bronchopulmonary aspergillosis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Gastroenteritis salmonella | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Lower respiratory tract infection | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Lymph gland infection | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Osteomyelitis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pneumocystis jirovecii pneumonia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pneumonia | 1/15 (6.7%) | 1 | 2/10 (20%) | 2 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Pneumonia pneumococcal | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Sepsis | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Septic shock | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Sialoadenitis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Upper respiratory tract infection | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 3 |
| Urinary tract infection | 1/15 (6.7%) | 3 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Urosepsis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Viral rash | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Cystitis radiation | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Femur fracture | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Haemolytic transfusion reaction | 0/15 (0%) | 0 | 2/10 (20%) | 3 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Subdural haematoma | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 4 |
| Investigations | ||||||||
| Liver function test abnormal | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Troponin T increased | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Hypercalcaemia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Bone lesion | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Bone pain | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Joint effusion | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Synovitis | 1/15 (6.7%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Infected neoplasm | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pancreatic carcinoma metastatic | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Nervous system disorders | ||||||||
| Ataxia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Autonomic neuropathy | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Balance disorder | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Encephalitis autoimmune | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Headache | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 2 |
| Seizure | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/15 (6.7%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Haematuria | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 4/43 (9.3%) | 4 |
| Renal impairment | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chylothorax | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Dyspnoea | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Pleural effusion | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Pleuritic pain | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Pneumonia aspiration | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pneumonitis | 1/15 (6.7%) | 1 | 1/10 (10%) | 3 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Respiratory failure | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Pemphigoid | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Toxic epidermal necrolysis | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg | Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg | Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/15 (100%) | 9/10 (90%) | 7/7 (100%) | 40/43 (93%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/15 (13.3%) | 2 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 9/43 (20.9%) | 21 |
| Haemolysis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Haemolytic anaemia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Leukopenia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 33 |
| Lymphopenia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Neutropenia | 1/15 (6.7%) | 2 | 1/10 (10%) | 2 | 0/7 (0%) | 0 | 9/43 (20.9%) | 21 |
| Thrombocytopenia | 2/15 (13.3%) | 2 | 2/10 (20%) | 5 | 0/7 (0%) | 0 | 7/43 (16.3%) | 10 |
| Thrombocytosis | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Cardiac disorders | ||||||||
| Atrial flutter | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Cardiac tamponade | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pericardial effusion | 0/15 (0%) | 0 | 1/10 (10%) | 2 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Vertigo | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Eye disorders | ||||||||
| Dry eye | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Eyelid ptosis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Vision blurred | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Abdominal pain | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Abdominal pain upper | 2/15 (13.3%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Ascites | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 3 |
| Coeliac disease | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Constipation | 2/15 (13.3%) | 2 | 2/10 (20%) | 2 | 1/7 (14.3%) | 1 | 9/43 (20.9%) | 10 |
| Diarrhoea | 6/15 (40%) | 10 | 2/10 (20%) | 2 | 2/7 (28.6%) | 2 | 10/43 (23.3%) | 14 |
| Dry mouth | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Dysphagia | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Haemorrhoids | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Immune-mediated enterocolitis | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 1/43 (2.3%) | 3 |
| Lip ulceration | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Nausea | 4/15 (26.7%) | 4 | 3/10 (30%) | 3 | 1/7 (14.3%) | 1 | 7/43 (16.3%) | 9 |
| Oral blood blister | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Paraesthesia oral | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Rectal haemorrhage | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Rectal polyp | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Stomatitis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Tongue geographic | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Vomiting | 1/15 (6.7%) | 2 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 8/43 (18.6%) | 12 |
| General disorders | ||||||||
| Chills | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Complication associated with device | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Fatigue | 5/15 (33.3%) | 5 | 2/10 (20%) | 2 | 0/7 (0%) | 0 | 9/43 (20.9%) | 12 |
| Influenza like illness | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Infusion site irritation | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Non-cardiac chest pain | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Oedema peripheral | 0/15 (0%) | 0 | 2/10 (20%) | 3 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Peripheral swelling | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 5 |
| Pyrexia | 3/15 (20%) | 3 | 1/10 (10%) | 2 | 0/7 (0%) | 0 | 3/43 (7%) | 4 |
| Immune system disorders | ||||||||
| Drug hypersensitivity | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 2/43 (4.7%) | 3 |
| Infections and infestations | ||||||||
| Campylobacter sepsis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Cellulitis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Conjunctivitis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Conjunctivitis bacterial | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Folliculitis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Furuncle | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Herpes simplex | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Herpes zoster | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Lower respiratory tract infection | 0/15 (0%) | 0 | 2/10 (20%) | 2 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Ludwig angina | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Nail bed infection | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Oral candidiasis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 4/43 (9.3%) | 4 |
| Oral herpes | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 1/43 (2.3%) | 1 |
| Otitis externa | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pneumonia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Respiratory tract infection | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Sepsis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Sinusitis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Skin infection | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Upper respiratory tract infection | 5/15 (33.3%) | 6 | 3/10 (30%) | 3 | 1/7 (14.3%) | 1 | 5/43 (11.6%) | 7 |
| Urinary tract infection | 1/15 (6.7%) | 7 | 0/10 (0%) | 0 | 2/7 (28.6%) | 3 | 6/43 (14%) | 18 |
| Viral rhinitis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Viral upper respiratory tract infection | 2/15 (13.3%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Vulvitis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Vulvovaginal candidiasis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Concussion | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Contusion | 2/15 (13.3%) | 2 | 2/10 (20%) | 5 | 0/7 (0%) | 0 | 10/43 (23.3%) | 14 |
| Fall | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Limb injury | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Rib fracture | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Thermal burn | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Tooth fracture | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Traumatic haematoma | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Aspartate aminotransferase increased | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Blood alkaline phosphatase increased | 1/15 (6.7%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Blood creatinine increased | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 2/43 (4.7%) | 2 |
| Gamma-glutamyltransferase increased | 2/15 (13.3%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Human metapneumovirus test positive | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Lymphocyte count decreased | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 13 |
| Neutrophil count decreased | 0/15 (0%) | 0 | 1/10 (10%) | 2 | 1/7 (14.3%) | 1 | 3/43 (7%) | 27 |
| Platelet count decreased | 0/15 (0%) | 0 | 1/10 (10%) | 5 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Serum ferritin decreased | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Troponin increased | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Weight decreased | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 3/15 (20%) | 4 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 4/43 (9.3%) | 4 |
| Dehydration | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 2/43 (4.7%) | 2 |
| Diabetes mellitus inadequate control | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Hyperglycaemia | 1/15 (6.7%) | 1 | 2/10 (20%) | 2 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Hyperkalaemia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Hypoalbuminaemia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Hypoglycaemia | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Hypokalaemia | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 6/43 (14%) | 6 |
| Hypomagnesaemia | 2/15 (13.3%) | 3 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 3/43 (7%) | 4 |
| Hypophosphataemia | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Iron deficiency | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Tumour lysis syndrome | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 1/43 (2.3%) | 1 |
| Type 2 diabetes mellitus | 2/15 (13.3%) | 2 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Vitamin B12 deficiency | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/15 (6.7%) | 1 | 2/10 (20%) | 2 | 0/7 (0%) | 0 | 4/43 (9.3%) | 5 |
| Arthritis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Back pain | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 5/43 (11.6%) | 8 |
| Flank pain | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Joint swelling | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 3 |
| Muscle spasms | 2/15 (13.3%) | 2 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 3/43 (7%) | 6 |
| Musculoskeletal chest pain | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 1/43 (2.3%) | 1 |
| Musculoskeletal pain | 1/15 (6.7%) | 2 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Neck pain | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 1/43 (2.3%) | 1 |
| Pain in extremity | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 4/43 (9.3%) | 6 |
| Synovitis | 1/15 (6.7%) | 3 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Benign neoplasm | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Skin cancer | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Tumour pain | 1/15 (6.7%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Nervous system disorders | ||||||||
| Ageusia | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Aphasia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Dizziness | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 3 |
| Dizziness postural | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Dysgeusia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Headache | 1/15 (6.7%) | 1 | 3/10 (30%) | 3 | 0/7 (0%) | 0 | 4/43 (9.3%) | 5 |
| Memory impairment | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Neuralgia | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 2 |
| Paraesthesia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Peripheral sensory neuropathy | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Presyncope | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Restless legs syndrome | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Somnolence | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Syncope | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 3/43 (7%) | 3 |
| Psychiatric disorders | ||||||||
| Anxiety | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Depressed mood | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Depression | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Insomnia | 2/15 (13.3%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Renal and urinary disorders | ||||||||
| Dysuria | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Haematuria | 2/15 (13.3%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 4/43 (9.3%) | 4 |
| Nocturia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Urinary hesitation | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Urinary retention | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Erectile dysfunction | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Vaginal haemorrhage | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic obstructive pulmonary disease | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Cough | 4/15 (26.7%) | 4 | 3/10 (30%) | 3 | 0/7 (0%) | 0 | 7/43 (16.3%) | 10 |
| Dysphonia | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Dyspnoea | 0/15 (0%) | 0 | 2/10 (20%) | 2 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Dyspnoea exertional | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Epistaxis | 1/15 (6.7%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Haemoptysis | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Laryngeal inflammation | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Nasal polyps | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Oropharyngeal pain | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pneumonitis | 2/15 (13.3%) | 2 | 1/10 (10%) | 3 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Productive cough | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Dry skin | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Ecchymosis | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Erythema | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Hyperhidrosis | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Photosensitivity reaction | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Pruritus | 2/15 (13.3%) | 2 | 1/10 (10%) | 1 | 1/7 (14.3%) | 1 | 2/43 (4.7%) | 2 |
| Purpura | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Rash | 2/15 (13.3%) | 5 | 1/10 (10%) | 2 | 2/7 (28.6%) | 3 | 3/43 (7%) | 5 |
| Rash macular | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 1/43 (2.3%) | 1 |
| Rash maculo-papular | 1/15 (6.7%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 3/43 (7%) | 3 |
| Rash pruritic | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Rosacea | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Skin exfoliation | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Skin lesion | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 1/7 (14.3%) | 1 | 0/43 (0%) | 0 |
| Skin ulcer | 0/15 (0%) | 0 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Vascular disorders | ||||||||
| Haematoma | 1/15 (6.7%) | 2 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Hot flush | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
| Hypertension | 1/15 (6.7%) | 1 | 1/10 (10%) | 1 | 0/7 (0%) | 0 | 2/43 (4.7%) | 2 |
| Hypotension | 0/15 (0%) | 0 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 4/43 (9.3%) | 4 |
| Orthostatic hypotension | 1/15 (6.7%) | 1 | 0/10 (0%) | 0 | 0/7 (0%) | 0 | 0/43 (0%) | 0 |
Limitations/Caveats
More Information
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | BeiGene |
| Phone | +1-877-828-5568 |
| clinicaltrials@beigene.com |
- BGB-3111_BGB-A317_Study_001