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Trial record 1 of 1 for:    NCT02660034
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The Safety, Pharmacokinetics and Antitumor Activity of BGB-A317 in Combination With BGB-290 in Participants With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02660034
Recruitment Status : Active, not recruiting
First Posted : January 21, 2016
Last Update Posted : April 21, 2020
Sponsor:
Collaborator:
Myriad Genetic Laboratories, Inc.
Information provided by (Responsible Party):
BeiGene

Tracking Information
First Submitted Date  ICMJE January 11, 2016
First Posted Date  ICMJE January 21, 2016
Last Update Posted Date April 21, 2020
Actual Study Start Date  ICMJE February 2, 2016
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2020)
  • Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: from the day of first administration of study drugs up to 30 days after the last administration of pamiparib and up to 90 days after the last administration of tislelizumab. ]
    Safety and tolerability as assessed by the incidence and nature of Adverse Events (AEs).
  • Part A: Incidence and nature of Dose Limiting Toxicities [ Time Frame: from the day of first administration of study drugs up to 30 days after the last administration of pamiparib and up to 90 days after the last administration of tislelizumab. ]
  • Part A: Determination of maximum tolerated dose of the combination of tislelizumab and pamiparib [ Time Frame: from the day of first administration of study drugs up to 30 days after the last administration of pamiparib and up to 90 days after the last administration of tislelizumab. ]
  • Part B: Disease response as determined by Overall Response Rate (ORR) per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the ORR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part B: Disease response as determined by Progression Free Survival (PFS) per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the PFS. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part B: Disease response as determined by Duration of Response (DOR) per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the DOR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part B: Disease response as determined by Disease Control Rate (DCR) per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the DCR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part B: Disease response as determined by Clinical Benefit Rate (CBR) per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the CBR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part B: Disease response as determined by overall survival (OS) [ Time Frame: From randomisation until the participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the OS.
Original Primary Outcome Measures  ICMJE
 (submitted: January 17, 2016)
  • Phase 1A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: from signing the informed consent form (ICF) and throughout the study (2 years of active therapy) ]
  • Phase 1B: Objective Response Rate (ORR) as evaluated by the investigators separately for each arm [ Time Frame: Every 9 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 24, 2019)
  • Part A: Pharmacokinetic parameters, including but not limited to Ctrough of tislelizumab [ Time Frame: pre-dose in Cycle 1, 2, 3, 4, 5, 9 & 17 and at 4 hours in Cycles 2, 3 & 4 (each cycle is 21 days) ]
  • Part A: Pharmacokinetic parameters, including but not limited to Cmax of pamiparib [ Time Frame: pre-dose in Cycle 2 & 3, and at 0.5, 1, 2, 4 & 7 hours post dose in Cycle 2 (each cycle is 21 days) ]
  • Part A: Pharmacokinetic parameters, including but not limited to Tmax of pamiparib [ Time Frame: pre-dose in Cycle 2 & 3, and at 0.5, 1, 2, 4 & 7 hours post dose in Cycle 2 (each cycle is 21 days) ]
  • Part A: Pharmacokinetic parameters, including but not limited to Ctrough of pamiparib [ Time Frame: pre-dose in Cycle 2 & 3, and at 0.5, 1, 2, 4 & 7 hours post dose in Cycle 2 (each cycle is 21 days) ]
  • Part A: Disease response as determined by Overall Response Rate per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the ORR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part A: Disease response as determined by Progression Free Survival per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the PFS. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part A: Disease response as determined by Duration of Response per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the DOR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part A: Disease response as determined by Disease Control Rate per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the DCR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part A: Disease response as determined by Clinical Benefit Rate per RECIST Version 1.1 [ Time Frame: From randomisation until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the CBR. Radiological assessment of tumor response should be performed approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks from screening until unequivocal PD is documented, the participant starts new anti-cancer therapies, participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment.
  • Part A: Disease response as determined by overall survival [ Time Frame: From randomisation until the participant withdraws consent from the trial, date of death from any cause, or completes a total of 2 years treatment. ]
    Anti-tumor activity as determined by the OS.
  • Part A: Immunogenicity of tislelizumab [ Time Frame: Blood for anti-tislelizumab antibodies should be collected within 24 hours before the start of the first dose of tislelizumab in Cycle 1, and Day 8 of Cycle 1, Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9 and Cycle 17 ]
  • Part B: Safety and tolerability as assessed by the incidence and nature of AEs [ Time Frame: from the day of first administration of study drugs up to 30 days after the last administration of pamiparib and up to 90 days after the last administration of tislelizumab. ]
  • Part B: Pharmacokinetic parameters, including but not limited to Ctrough of tislelizumab and Pamiparib [ Time Frame: Tislelizumab: Pre-dose in Cycle 1 (day 1 and day 8), and Cycles 2, 3, 4 5, 9 & 17. At 4 hours in Cycles 1 & 5. Pamiparib: Pre-dose and 2 hours post dose in Cycles 1 and 2 (each cycle is 21 days) ]
  • Part B: Immunogenicity of tislelizumab [ Time Frame: Cycle 1 (Day 1 & Day 8), and Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9 and Cycle 17 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2016)
  • Phase 1A and 1B: Serum concentrations of BGB-A317 [ Time Frame: pre-dose and at 4 hours in Cycles 2 (each cycle is 21 days), 3 and 4 ]
  • Phase 1A and 1B: Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration (AUClast) at steady state for BGB-290 [ Time Frame: Part A and B: day 1 in Cycle 2 (each cycle is 21 days), and 3 ]
  • Phase 1A and 1B: Maximum plasma concentration (Cmax) at steady state for BGB-290 [ Time Frame: Part A and B: day 1 in Cycle 2 (each cycle is 21 days), and 3 ]
  • Phase 1A and 1B: Time to reach maximum plasma concentration (tmax) at steady state for BGB-290 [ Time Frame: Part A and B: day 1 in Cycle 2 (each cycle is 21 days), and 3 ]
  • Phase 1A and 1B: disease control rate (DCR) [ Time Frame: Every 9 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months ]
  • Phase 1A and 1B: Clinical benefit rate (CBR) [ Time Frame: Every 9 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Safety, Pharmacokinetics and Antitumor Activity of BGB-A317 in Combination With BGB-290 in Participants With Advanced Solid Tumors
Official Title  ICMJE 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
Brief Summary The Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Participants With Advanced Solid Tumors
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE
  • Biological: tislelizumab
    Other Name: BGB-A317
  • Drug: pamiparib
    Other Name: BGB-290
Study Arms  ICMJE
  • Experimental: Phase 1A
    Approximately 50 participants for the dose escalation until maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) determination
    Interventions:
    • Biological: tislelizumab
    • Drug: pamiparib
  • Experimental: Phase 1B
    Approximately 180 participants for expansion in eight selected arms with nine cohorts.
    Interventions:
    • Biological: tislelizumab
    • Drug: pamiparib
Publications * Friedlander M, Meniawy T, Markman B, Mileshkin L, Harnett P, Millward M, Lundy J, Freimund A, Norris C, Mu S, Wu J, Paton V, Gao B. Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. Lancet Oncol. 2019 Sep;20(9):1306-1315. doi: 10.1016/S1470-2045(19)30396-1. Epub 2019 Aug 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 20, 2020)
229
Original Estimated Enrollment  ICMJE
 (submitted: January 17, 2016)
124
Estimated Study Completion Date  ICMJE September 15, 2020
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Participants have 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 have the below specified histologically confirmed malignancies that have progressed to the advanced or metastatic stage.

    1. In Part A, the participants must have an advanced malignancy including but not limited to high-grade serous cancer of the ovary, fallopian tube, or peritoneum, triple negative breast 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 one of the eight expansion arms must have 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 meet the following criteria:

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

    • Note: participants may have received additional therapy after the last platinum-containing regimen if the other eligibility criteria are met.

    ii. Must have platinum-sensitive recurrent disease and must not have progressed (by RECIST v1.1 criteria) within 6 months of the completion of the last platinum containing line of treatment • Note: participants may receive additional non-platinum based chemotherapy for recurrence after prior last platinum containing regimen if the criteria for platinum sensitivity are met.

    iii. Arm 1a: Participants with relapsed, platinum-sensitive high grade epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) with either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with HRD • If HRD or BRCA1/2 mutation status from archival tissue is unknown or has not been previously evaluated, then the archival tissue must undergo tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result is BRCA1/2 or HRD positive the participant will be eligible for enrollment in Arm 1a iv. Arm 1b: Participants with relapsed, platinum-sensitive high grade EOC who otherwise meet the above criteria and are without known germline or somatic BRCA1/2 mutations and without HRD mutation

    Arm 2: Participants with triple negative breast cancer must meet 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 are met.

    ii. Participants who have 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 is unknown or has not been previously evaluated, then the archival tissue must undergo tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result is HRD positive, then the participant will be eligible for enrollment in Arm 2
    • If archival tissue is not available and the participant submits a fresh tumor biopsy, then the diagnostic test needs 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 meet 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 is used more than once, this will be 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 do not need to be checked if the participant has undergone surgical castration for > 4 months. Participants receiving chemical castration should have 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 (LHRH) antagonist/agonist is to be continued in these participants

    • Participants with only non-measurable bone lesions must have disease progression based on PCWG3 with 2 or more new lesions or have prostate-specific antigen (PSA) 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 is unknown or has not been previously evaluated, then the archival tissue must undergo tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result is HRD positive, then the participant will be eligible for enrollment in Arm 3
    • If archival tissue is not available and the participant submits a fresh tumor biopsy, then the diagnostic test needs to demonstrate somatic BRCA1/2 mutation or HRD positivity.

    Arm 4: Participants with extensive-stage disease small cell lung cancer (SCLC) must meet the following criterion:

    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 (HER2)-negative gastric or gastroesophageal junction cancer must meet 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 meet 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 meet the following criteria:

    i. Received at least one 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 can be considered for the study even if platinum-naive

    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 MMR deficient or HRD positive) must meet 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 will approve tumor types for Arm 8 prior to screening

    • Note: Excluded tumor types include participants with bone or soft tissue sarcoma; central nervous system (CNS) malignancies; colorectal cancer (except microsatellite instability-high [MSI H] 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 been 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 AEs have either returned to baseline or
  5. At least 2 weeks from palliative radiotherapy
  6. Participants must have 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 are recommended at baseline in participants with readily accessible tumor lesions and who consent 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 agree to provide fresh blood sample at the baseline for the evaluation of BRCA mutations and/or confirmation of prior BRCA results or other homologous recombination deficiency mutations even if it was previously tested
  7. Participants must have 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 use separate disease-specific criteria
  8. Male or female ≥ 18 years of age on the day of signing informed consent
  9. Must have an ECOG Performance Status (PS) ≤ 1
  10. Must have a life expectancy ≥ 12 weeks
  11. Must have adequate organ function
  12. Females of childbearing potential must be 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 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 be 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 avoid sperm donation for the duration of the study and for at least 6 months after last study drug
  14. Females must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration

Key Exclusion criteria:

  1. Platinum-resistant/refractory disease, defined as progressive disease at the first tumor assessment while receiving platinum-containing chemotherapy
  2. Participant has history of severe hypersensitivity reactions to other monoclonal antibodies (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) which have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy and specific laboratory abnormalities).
  6. Concurrent participation in another therapeutic clinical trial.
  7. Prior malignancy within the previous 2 years except for locally curable non-melanoma dermatologic cancers that have 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 MRI of the brain and spinal cord is required for SCLC participants enrolled in Arm 4 if they have a history of CNS disease.

    Note: Participants with previously treated CNS metastatic disease are eligible for any arm if CNS metastatic disease is asymptomatic, clinically stable, and does 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. The exception to this criterion are participants eligible for Arm 9; where they may have received either a PD-1 inhibitor or PD-L1 inhibitor.
  10. Active autoimmune diseases or history of autoimmune diseases that may relapse

    Note: Participants with the following diseases are not excluded and may proceed 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 (eg, vitiligo, psoriasis, alopecia).
    5. Any other disease that is 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 are currently or have previously been on any of the following steroid regimens are 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 (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, 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, etc.
  13. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
  14. History of non-viral hepatitis or cirrhosis.
  15. Positive human immunodeficiency virus (HIV) status.
  16. A known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  17. History of alcohol abuse.
  18. Underlying medical conditions or alcohol or drug abuse or dependence that, in the investigator's opinion, will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or adverse events; 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 gastrointestinal illnesses that would preclude the absorption of pamiparib, which is an oral agent.
  20. Has 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 have 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   New Zealand,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02660034
Other Study ID Numbers  ICMJE BGB-A317/BGB-290_Study_001
2017-003580-35 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Myriad Genetic Laboratories, Inc.
Investigators  ICMJE
Principal Investigator: Michael Friedlander, MD Prince of Wales Hospital
PRS Account BeiGene
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP