Clinical Trials /

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

NCT02660034

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Pancreatic Adenocarcinoma
  • Primary Peritoneal Carcinoma
  • Prostate Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: The Safety, Pharmacokinetics and Antitumor Activity of BGB-A317 in Combination With BGB-290 in Participants With Advanced Solid Tumors
  • Official Title: A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BGB-A317/BGB-290_Study_001
  • SECONDARY ID: 2017-003580-35
  • NCT ID: NCT02660034

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
tislelizumabBGB-A317Phase 1A
pamiparibBGB-290Phase 1A

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Phase 1AExperimentalApproximately 50 participants for the dose escalation until maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) determination
  • tislelizumab
  • pamiparib
Phase 1BExperimentalApproximately 180 participants for expansion in eight selected arms with nine cohorts.
  • tislelizumab
  • pamiparib

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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 Issue:
Description:Safety and tolerability as assessed by the incidence and nature of Adverse Events (AEs).

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description:Anti-tumor activity as determined by the OS.
Measure: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
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BeiGene

Trial Keywords

  • Dose Escalation
  • Dose Expansion
  • BGB-A317
  • BGB-290

Last Updated

February 26, 2020