Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency

• Sponsor: BeiGene (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03712930
• Collaborator: (none)
• Enrollment: 13
• Locations: 9
• Arm: 1
• Actual Duration (Months): 18.9
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is designed to evaluate the efficacy of pamiparib in participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). All participants will receive pamiparib. The purpose of this study is to demonstrate that pamiparib will improve Objective Response Rate (ORR) and Prostate-Specific Antigen (PSA) response rate

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-Resistant Prostate Cancer (mCRPC); Homologous Recombination Deficiency (HRD)	Drug: Pamiparib	Phase 2

Detailed Description

This is a global, Phase 2, open-label study of pamiparib in approximately 100 participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). Participants in Cohort 1 will include 50 mCRPC participants with CTC-HRD-positive, measurable metastatic disease (soft tissue with/without bone lesions), and positive BRCA1/2 mutation or negative/unknown BRCA1/2 mutation. Cohort 2 will include 30 mCRPC CTC-HRD positive participants with bone metastasis only and positive or negative/unknown BRCA1/2. Cohort 3 and 4 will include 20 mCRPC CTC-HRD negative/unknown participants with BRCA1/2 positive mutations, metastatic disease (measurable soft tissue with/without bone), and bone only. Participants will undergo PSA level assessments approximately every 4 weeks as well as tumor assessments every 8 weeks for 24 weeks and the every 12 weeks, or as clinically indicated. Administration of pamiparib will continue until disease progression, unacceptable toxicity, death or another discontinuation criterion is met.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Single-Arm Study of BGB-290 (BGB-290) for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Homologous Recombination Deficiency (HRD)
• Actual Study Start Date: Feb 5, 2019
• Actual Primary Completion Date: Aug 6, 2020
• Actual Study Completion Date: Sep 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pamiparib Participants will receive pamiparib for a period up to 1 year	Drug: Pamiparib; 60 mg orally twice daily (BID); Other Names: BGB-290

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) Determined by Independent Review Committee [Up to 1 year and 6 months]

   ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by an Independent Review Committee (IRC).

2. Prostate-Specific Antigen (PSA) Response Rate [Up to 1 year and 6 months]

   PSA response rate is defined as the percentage of participants with PSA decline ≥ 50% from baseline [confirmed by a second PSA value ≥ 3 weeks later] for CTC-HRD-positive participants with or without measurable disease.

Secondary Outcome Measures

1. Duration of Response (DOR) by IRC [Up to 1 year and 7 months]

   DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to radiographic disease progression or death due to any cause, whichever occurs first.

2. Objective Response Rate by Investigator [Up to 1 year and 6 months]

   ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by the investigator.

3. Time to Objective Response by Investigator [Up to 1 year and 6 months]

   Time to objective response is defined as the time from the date of the first dose of study drug to the first documented confirmed response of CR or PR assessed by the investigator and summarized for participants who have achieved a confirmed objective response.

4. Clinical Benefit Rate By Investigator [Up to 1 year and 6 months]

   Clinical Benefit Rate is the percentage of participants who achieved confirmed CR, PR, or SD or NON-CR/NON-PD. The minimum interval for confirmed CR and PR is 4 weeks and the measurement of SD or NON-CR/NON-PD is 7 weeks after first dose date.

5. Time to PSA Response [Up to 1 year and 6 months]

   Time to PSA response is defined as the time from the date of the first dose of study drug to the first PSA decline ≥ 50% that is subsequently confirmed. Assessments are summarized for participants who have achieved a confirmed PSA response.

6. Duration of PSA Response [Up to 1 year and 7 months]

   Duration of PSA response is defined as the time from the date of the earliest documented PSA response (that is subsequently confirmed) to PSA progression or death due to any cause, whichever occurs first. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 μg/L above the nadir (or above the baseline for participants with no PSA decline) after12 weeks, confirmed by a second value ≥ 3 weeks later. The nadir is defined as the lowest value at or after baseline.

7. Time to PSA Progression [Up to 1 year and 7 months]

   Time to PSA progression is defined as the time from the date of the first dose of study drug to a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline for participants with no PSA decline) after 12 weeks, confirmed by a second value ≥ 3 weeks later. Death for the participants with no PSA progression is also considered as an event.

8. Time to Symptomatic Skeletal Event [Up to 1 year and 7 months]

   Time to symptomatic skeletal event (SSE) is defined as time from the date of the first dose of study drug to the first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.

9. Radiographic Progression-Free Survival by IRC [Up to 1 year and 7 months]

   Radiographic progression-free survival is defined as the time from the date of the first dose of study drug to radiographic disease progression by IRC or death due to any cause, whichever occurs first.

10. Overall Survival (OS) [Up to 1 year and 7 months]

    Overall survival is defined as the time from the date of the first dose of study drug to death due to any cause.

11. Number of Participants With Treatment-Emergent Adverse Events Graded According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 [From the date of first Pamiparib dose until 30 days after the last dose or initiation of new anti-cancer therapy, whichever occurs first. (Up to 1 year and 7 months)]

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Men (≥ 18 years of age) with histologically or cytologically confirmed adenocarcinoma or poorly differentiated adenocarcinoma of the prostate without neuroendocrine differentiation with HRD deficiency by CTC-HRD assay and/or deleterious germline or somatic mutation in BRCA1 or BRCA2; mCRPC measurable disease and/or bone disease. • PSA progression with ≥ 3 rising PSA levels with ≥ 1 week between determinations and a screening PSA ≥ 2 μg/L (2 ng/mL).

• Must be surgically or medically castrated with serum testosterone levels of ≤1.73 nmol/L (50 ng/dL), must have received ≥ 1 prior androgen receptor-targeted therapy, and must have received ≥ 1 taxane-based therapy.

• mCRPC with 1 or 2 of the following:

• Measurable disease per RECIST v1.1

• Bone disease

• CTC-HRD+ or BRCA1/2 mutation

• PSA progression (PCWG3 criteria)

• ≥1 androgen receptor-targeted therapy (eg, abiraterone acetate/prednisone or enzalutamide) for mCRPC with progressive disease

• ≥1 taxane for metastatic prostate cancer

Key Exclusion Criteria:

• Chemotherapy, hormonal therapy, biologic therapy, radionuclide therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or herbal remedies ≤ 5 half-lives if the half-life is known, ≤ 14 days if not known, before start of study treatment

• Continued treatment with a bisphosphonate or denosumab is allowed, if administered at a stable dose > 28 days before start of study treatment

• Radiotherapy ≤ 21 days (≤ 14 days, if single fraction of radiotherapy) before start of study treatment

Prior treatment for prostate cancer with any of the following:

• poly ADP ribose polymerase (PARP) inhibitor

• Platinum

• Cyclophosphamide

• Mitoxantrone

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Cancer and Blood Center	Athens	Georgia	United States	30607
2	Montefiore Einstein Cancer Center	Bronx	New York	United States	10461
3	University of Washington	Seattle	Washington	United States	98195
4	Gosford Hospital	Gosford	New South Wales	Australia	2250
5	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
6	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
7	Icon Cancer Care Foundation	South Brisbane	Queensland	Australia	044101
8	Pan American Oncology Trials, LLC	Rio Piedras		Puerto Rico	935
9	L Hospitalet de Llobregat	Barcelona		Spain	8035

Sponsors and Collaborators

• BeiGene

Investigators

• Principal Investigator: Study Director, Guy's and St Thomas' NHS Foundation Trust

Study Documents (Full-Text)

• Study Protocol - Oct 16, 2018
• Statistical Analysis Plan - Nov 2, 2020

More Information

Publications

None provided.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03712930
• Other Study ID Numbers: BGB-290-202; 2018-002587-28
• First Posted: Oct 19, 2018
• Last Update Posted: Nov 17, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	Eighteen subjects were screened; 5 subjects failed screening and 13 subjects were dosed.
Pre-assignment Detail	All subjects enrolled had unknown BRCA1/2 status at study entry and were assigned to cohorts 1B or 2B; there were no subjects known to be BRCA1/2 positive at enrollment.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Period Title: Overall Study
STARTED	13
COMPLETED	0
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Overall Participants	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.3 (9.49)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	13 100%
Race/Ethnicity, Customized (Count of Participants)
Race: American Indian or Alaska Native, White	1 7.7%
Race: White	7 53.8%
Race: Not Reported	1 7.7%
Race: Unknown	3 23.1%
Race: Other	1 7.7%
Ethnicity: Not Hispanic or Latino	7 53.8%
Hispanic or Latino	3 23.1%
Not Reported/Unknown	3 23.1%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) Determined by Independent Review Committee
Description	ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by an Independent Review Committee (IRC).
Time Frame	Up to 1 year and 6 months

Outcome Measure Data

Analysis Population Description

Efficacy-Evaluable Analysis Set: includes all participants in the Safety Analysis Set who had measurable disease at baseline and at least 1 post-baseline tumor assessment, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before tumor assessment. Participants with available data were included in the analysis.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	12
Number [Percentage of participants]	0 0%

2. Primary Outcome

Title	Prostate-Specific Antigen (PSA) Response Rate
Description	PSA response rate is defined as the percentage of participants with PSA decline ≥ 50% from baseline [confirmed by a second PSA value ≥ 3 weeks later] for CTC-HRD-positive participants with or without measurable disease.
Time Frame	Up to 1 year and 6 months

Outcome Measure Data

Analysis Population Description

PSA-Evaluable Analysis Set: includes all participants in the Safety Analysis Set with ≥3 rising PSA levels with ≥ 1 week between determinations and screening PSA ≥ 2 μg/L) and who had at least 1 post-baseline PSA measurement unless they permanently discontinue pamiparib or the study early due to clinical progression or death before completed PSA assessment.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Number [Percentage of participants]	0 0%

3. Secondary Outcome

Title	Duration of Response (DOR) by IRC
Description	DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to radiographic disease progression or death due to any cause, whichever occurs first.
Time Frame	Up to 1 year and 7 months

Outcome Measure Data

Analysis Population Description

Efficacy-Evaluable Analysis Set: includes all participants in the Safety Analysis Set who had measurable disease at baseline and at least 1 post-baseline tumor assessment, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before tumor assessment. Participants with available data were included in the analysis.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	12
Number [Months]	NA

4. Secondary Outcome

Title	Objective Response Rate by Investigator
Description	ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by the investigator.
Time Frame	Up to 1 year and 6 months

Outcome Measure Data

Analysis Population Description

Efficacy-Evaluable Analysis Set: includes all participants in the Safety Analysis Set who had measurable disease at baseline and at least 1 post-baseline tumor assessment, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before tumor assessment. Participants with available data were included in the analysis.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	12
Number [Percentage of participants]	0 0%

5. Secondary Outcome

Title	Time to Objective Response by Investigator
Description	Time to objective response is defined as the time from the date of the first dose of study drug to the first documented confirmed response of CR or PR assessed by the investigator and summarized for participants who have achieved a confirmed objective response.
Time Frame	Up to 1 year and 6 months

Outcome Measure Data

Analysis Population Description

Efficacy-Evaluable Analysis Set: includes all participants in the Safety Analysis Set who had measurable disease at baseline and at least 1 post-baseline tumor assessment, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before tumor assessment. Participants with available data were included in the analysis.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	12
Number [Months]	NA

6. Secondary Outcome

Title	Clinical Benefit Rate By Investigator
Description	Clinical Benefit Rate is the percentage of participants who achieved confirmed CR, PR, or SD or NON-CR/NON-PD. The minimum interval for confirmed CR and PR is 4 weeks and the measurement of SD or NON-CR/NON-PD is 7 weeks after first dose date.
Time Frame	Up to 1 year and 6 months

Outcome Measure Data

Analysis Population Description

Efficacy-Evaluable Analysis Set: includes all participants in the Safety Analysis Set who had measurable disease at baseline and at least 1 post-baseline tumor assessment, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before tumor assessment. Participants with available data were included in the analysis.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	12
Number [Percentage of participants]	25 192.3%

7. Secondary Outcome

Title	Time to PSA Response
Description	Time to PSA response is defined as the time from the date of the first dose of study drug to the first PSA decline ≥ 50% that is subsequently confirmed. Assessments are summarized for participants who have achieved a confirmed PSA response.
Time Frame	Up to 1 year and 6 months

Outcome Measure Data

Analysis Population Description

PSA-Evaluable Analysis Set: includes all participants in the Safety Analysis Set with ≥3 rising PSA levels with ≥ 1 week between determinations and screening PSA ≥ 2 μg/L and who had at least 1 post-baseline PSA measurement, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before completed PSA assessment.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Number [Months]	NA

8. Secondary Outcome

Title	Duration of PSA Response
Description	Duration of PSA response is defined as the time from the date of the earliest documented PSA response (that is subsequently confirmed) to PSA progression or death due to any cause, whichever occurs first. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 μg/L above the nadir (or above the baseline for participants with no PSA decline) after12 weeks, confirmed by a second value ≥ 3 weeks later. The nadir is defined as the lowest value at or after baseline.
Time Frame	Up to 1 year and 7 months

Outcome Measure Data

Analysis Population Description

PSA-Evaluable Analysis Set: includes all participants in the Safety Analysis Set with ≥3 rising PSA levels with ≥ 1 week between determinations and screening PSA ≥ 2 μg/L) and who had at least 1 post-baseline PSA measurement, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before completed PSA assessment.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Number [Months]	NA

9. Secondary Outcome

Title	Time to PSA Progression
Description	Time to PSA progression is defined as the time from the date of the first dose of study drug to a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline for participants with no PSA decline) after 12 weeks, confirmed by a second value ≥ 3 weeks later. Death for the participants with no PSA progression is also considered as an event.
Time Frame	Up to 1 year and 7 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set : includes all participants enrolled into the study who received any dose of pamiparib.

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Mean (Standard Deviation) [Months]	3.13 (1.533)

10. Secondary Outcome

Title	Time to Symptomatic Skeletal Event
Description	Time to symptomatic skeletal event (SSE) is defined as time from the date of the first dose of study drug to the first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.
Time Frame	Up to 1 year and 7 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: includes all participants enrolled in the study who received any dose of pamiparib

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Number [Months]	NA

11. Secondary Outcome

Title	Radiographic Progression-Free Survival by IRC
Description	Radiographic progression-free survival is defined as the time from the date of the first dose of study drug to radiographic disease progression by IRC or death due to any cause, whichever occurs first.
Time Frame	Up to 1 year and 7 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set : includes all participants enrolled in the study who received any dose of pamiparib

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Median (95% Confidence Interval) [Months]	2.6

12. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the time from the date of the first dose of study drug to death due to any cause.
Time Frame	Up to 1 year and 7 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: includes all participants enrolled in the study who received any dose of pamiparib

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Median (95% Confidence Interval) [Months]	5.8

13. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events Graded According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
Time Frame	From the date of first Pamiparib dose until 30 days after the last dose or initiation of new anti-cancer therapy, whichever occurs first. (Up to 1 year and 7 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: includes all participants enrolled in the study who received any dose of pamiparib

Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
Measure Participants	13
Participants with at Least One TEAE	13 100%
Grade 3 or Higher	11 84.6%
Serious	6 46.2%
Leading to Death	1 7.7%
Leading to Treatment Discontinuation	3 23.1%
Leading to Dose Modification	11 84.6%
Leading to Dose Interruption	9 69.2%
Leading to Dose Reduction	5 38.5%
Treatment Related TEAEs	11 84.6%
Treatment Related Grade 3 or Higher	7 53.8%
Treatment Related Serious	1 7.7%
Treatment Related Leading to Death	0 0%
Treatment Related Leading to Treatment Discontinuation	3 23.1%
Treatment Related Leading to Dose Modification	7 53.8%
Treatment Related Leading to Dose Interruption	6 46.2%
Treatment Related Leading to Dose Reduction	3 23.1%

Adverse Events

Time Frame	From the date of first dose of Pamiparib until 30 days after the last dose or initiation of new anti-cancer therapy, whichever occurs first (up to approximately 1 year and 7 months)
Arm/Group Title	Pamiparib
Arm/Group Description	Participants received 60 mg pamiparib orally twice daily
All Cause Mortality
	Pamiparib
	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)
Serious Adverse Events
	Pamiparib
	Affected / at Risk (%)	# Events
Total	6/13 (46.2%)
Blood and lymphatic system disorders
Anemia	1/13 (7.7%)
Febrile neutropenia	1/13 (7.7%)
Neutropenia	1/13 (7.7%)
Pancytopenia	1/13 (7.7%)
General disorders
Pyrexia	2/13 (15.4%)
Peripheral swelling	1/13 (7.7%)
Infections and infestations
Oesophageal candidiasis	1/13 (7.7%)
Metabolism and nutrition disorders
Dehydration	1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/13 (7.7%)
Musculoskeletal chest pain	1/13 (7.7%)
Nervous system disorders
Hemiparesis	1/13 (7.7%)
Renal and urinary disorders
Hydronephrosis	1/13 (7.7%)
Ureteric obstruction	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Pamiparib
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Anaemia	7/13 (53.8%)
Neutropenia	2/13 (15.4%)
Thrombocytopenia	2/13 (15.4%)
Leukopenia	1/13 (7.7%)
Ear and labyrinth disorders
Vertigo	1/13 (7.7%)
Eye disorders
Dry eye	1/13 (7.7%)
Orbital oedema	1/13 (7.7%)
Gastrointestinal disorders
Nausea	7/13 (53.8%)
Diarrhoea	4/13 (30.8%)
Vomiting	4/13 (30.8%)
Abdominal pain	1/13 (7.7%)
Constipation	1/13 (7.7%)
Dry mouth	1/13 (7.7%)
Dyspepsia	1/13 (7.7%)
Gastrooesophageal reflux disease	1/13 (7.7%)
Rectal haemorrhage	1/13 (7.7%)
Rectal tenesmus	1/13 (7.7%)
General disorders
Fatigue	5/13 (38.5%)
Asthenia	1/13 (7.7%)
Infections and infestations
Urinary tract infection	2/13 (15.4%)
Oral candidiasis	1/13 (7.7%)
Investigations
Weight decreased	3/13 (23.1%)
Blood alkaline phosphatase increased	2/13 (15.4%)
Blood creatinine increased	2/13 (15.4%)
Aspartate aminotransferase increased	1/13 (7.7%)
Blood lactate dehydrogenase increased	1/13 (7.7%)
Platelet count decreased	1/13 (7.7%)
Metabolism and nutrition disorders
Decreased appetite	6/13 (46.2%)
Dehydration	1/13 (7.7%)
Hypocalcaemia	1/13 (7.7%)
Hypophosphataemia	1/13 (7.7%)
Malnutrition	1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Pain in extremity	2/13 (15.4%)
Back pain	1/13 (7.7%)
Flank pain	1/13 (7.7%)
Musculoskeletal pain	1/13 (7.7%)
Myalgia	1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/13 (7.7%)
Nervous system disorders
Dizziness	1/13 (7.7%)
Dysgeusia	1/13 (7.7%)
Headache	1/13 (7.7%)
Taste disorder	1/13 (7.7%)
Renal and urinary disorders
Haematuria	1/13 (7.7%)
Reproductive system and breast disorders
Pelvic pain	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/13 (7.7%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/13 (7.7%)

Limitations/Caveats

[Not Specified]

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.