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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02660034




Registration number
NCT02660034
Ethics application status
Date submitted
11/01/2016
Date registered
21/01/2016

Titles & IDs
Public title
The Safety, Pharmacokinetics and Antitumor Activity of BGB-A317 in Combination With BGB-290 in Participants With Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
2017-003580-35
Secondary ID [2] 0 0
BGB-A317/BGB-290_Study_001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Part A: Dose Escalation Phase - Participants received tislelizumab and pamiparib (dose escalation) until determination of the maximum tolerated dose/recommended Phase 2 dose.

Experimental: Part B: Dose Expansion Phase - Participants received tislelizumab and pamiparib (dose expansion).
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Number Of Participants Experiencing Adverse Events (AEs)
Timepoint [1] 0 0
From Day 1 up to 4 years and 7 months
Primary outcome [2] 0 0
Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)
Timepoint [2] 0 0
21 days following the first dose of tislelizumab and pamiparib in Cycle 1
Primary outcome [3] 0 0
Part B: Objective Response Rate (ORR)
Timepoint [3] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Primary outcome [4] 0 0
Part B: Progression-free Survival (PFS)
Timepoint [4] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Primary outcome [5] 0 0
Part B: Duration Of Response (DOR)
Timepoint [5] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Primary outcome [6] 0 0
Part B: Disease Control Rate (DCR)
Timepoint [6] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Primary outcome [7] 0 0
Part B: Clinical Benefit Rate (CBR)
Timepoint [7] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Primary outcome [8] 0 0
Part B: Overall Survival (OS)
Timepoint [8] 0 0
From Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)
Secondary outcome [1] 0 0
Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab
Timepoint [1] 0 0
Cycle 4 Day 1 (0 hours and 4 hours) post dose
Secondary outcome [2] 0 0
Part A: Ctrough Of Pamiparib
Timepoint [2] 0 0
Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Secondary outcome [3] 0 0
Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib
Timepoint [3] 0 0
Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Secondary outcome [4] 0 0
Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib
Timepoint [4] 0 0
Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Secondary outcome [5] 0 0
Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib
Timepoint [5] 0 0
Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Secondary outcome [6] 0 0
Part A: ORR
Timepoint [6] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Secondary outcome [7] 0 0
Part A: PFS
Timepoint [7] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Secondary outcome [8] 0 0
Part A: DCR
Timepoint [8] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Secondary outcome [9] 0 0
Part A: CBR
Timepoint [9] 0 0
Starting from Day 1 until disease progression (up to 4 years and 7 months)
Secondary outcome [10] 0 0
Part A: OS
Timepoint [10] 0 0
Starting from Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)
Secondary outcome [11] 0 0
Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Part B: Number Of Participants Experiencing AEs
Timepoint [12] 0 0
Day 1 of Cycle 1 up to 4 years and 7 months
Secondary outcome [13] 0 0
Part B: Ctrough Of Tislelizumab
Timepoint [13] 0 0
Cycle 4 Day 1 ( 0 hours and 4 hours post dose)
Secondary outcome [14] 0 0
Part B: Maximum Observed Plasma Concentration (Cmax) Of Tislelizumab
Timepoint [14] 0 0
Cycle 4 Day 1 ( 0 hours and 4 hours) post dose
Secondary outcome [15] 0 0
Part B: Ctrough Of Pamiparib
Timepoint [15] 0 0
Cycle 2 Day 1 (7 hours Post-dose)
Secondary outcome [16] 0 0
Part B: Cmax Of Pamiparib
Timepoint [16] 0 0
Cycle 2 (7 hours Post-dose)
Secondary outcome [17] 0 0
Part B: Percentage Of Participants With ADAs For Tislelizumab
Timepoint [17] 0 0
24 hours predose of Day 1 of every cycle

Eligibility
Key inclusion criteria
Key

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:

1. 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.
2. 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:

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

ii. 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.

iii. 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.

iv. 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:

i. 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.

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

iii. 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:

i. 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.

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

iii. 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.

iv. 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:

i. 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:

i. 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:

i. 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:

i. 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:

i. 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.
4. 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.
5. At least 2 weeks from palliative radiotherapy.
6. 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.
7. 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.
8. Male or female = 18 years of age on the day of signing informed consent.
9. Must have had an Eastern Cooperative Oncology Group Performance Status = 1.
10. Must have had a life expectancy = 12 weeks.
11. Must have had adequate organ function.
12. 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).
13. 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.
14. 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.
9. Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or PARP.
10. 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.
11. 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).
12. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, et cetera.
13. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, et cetera.
14. History of non-viral hepatitis or cirrhosis.
15. Positive human immunodeficiency virus status.
16. A known history of hepatitis B virus or hepatitis C virus infection.
17. History of alcohol abuse.
18. 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.
19. 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.
20. Had been administered a live vaccine within 4 weeks (28 days) of initiation of study therapy.
21. Any of the following cardiovascular criteria:

1. Current evidence of cardiac ischemia;
2. Current symptomatic pulmonary embolism;
3. Acute myocardial infarction = 6 months prior to Day 1;
4. Heart failure of New York Heart Association Classification III or IV = 6 months prior to Day 1;
5. Grade = 2 ventricular arrhythmia = 6 months prior to Day 1;
6. History of cerebrovascular accident within 6 months before first dose of study drugs.
22. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/09/2020
Sample size
Target
Accrual to date
Final
229
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Mid North Coast Cancer Institute - Coffs Harbour
Recruitment hospital [3] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [4] 0 0
Westmead Hospital - Parramatta
Recruitment hospital [5] 0 0
Prince of Wales - Randwick
Recruitment hospital [6] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [7] 0 0
Icon Cancer Care - Brisbane
Recruitment hospital [8] 0 0
Monash Health - Clayton
Recruitment hospital [9] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [10] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [3] 0 0
2298 - Newcastle
Recruitment postcode(s) [4] 0 0
- Parramatta
Recruitment postcode(s) [5] 0 0
- Randwick
Recruitment postcode(s) [6] 0 0
2065 - St Leonards
Recruitment postcode(s) [7] 0 0
4101 - Brisbane
Recruitment postcode(s) [8] 0 0
- Clayton
Recruitment postcode(s) [9] 0 0
- Melbourne
Recruitment postcode(s) [10] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
France
State/province [12] 0 0
Rennes
Country [13] 0 0
New Zealand
State/province [13] 0 0
Auckland
Country [14] 0 0
New Zealand
State/province [14] 0 0
Wellington
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Valencia
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Myriad Genetic Laboratories, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Friedlander M, Meniawy T, Markman B, Mileshkin L, ... [More Details]


Results not provided in https://clinicaltrials.gov/study/NCT02660034