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

NCT02660034 | Completed Phase 1 Results

• 2 other identifiers: BGB-A317/BGB-290_Study_0012017-003580-35
• Study Type: interventional
• Target: 229
• Locations: 6 countries
• Sites: 29

Brief Summary

This trial studied the safety, pharmacokinetics, and antitumor activity of the anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) BGB-A317 (tislelizumab) in combination with the poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor BGB-290 (pamiparib) in participants with advanced solid tumors.

Conditions

Solid Tumors

Keywords

Dose Escalation; Dose Expansion; BGB-A317; BGB-290; Tislelizumab; Pamiparib

Outcome Measures

Primary Outcomes (8)

• Part A: Number Of Participants Experiencing Adverse Events (AEs)

  An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

  From Day 1 up to 4 years and 7 months

• Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)

  DLT was defined as an AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and occurs during the first 21 days following the first dose of tislelizumab and pamiparib in Cycle 1 and meets protocol-specified criteria. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

  21 days following the first dose of tislelizumab and pamiparib in Cycle 1

• Part B: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with a best overall response of complete response (CR) and partial response (PR).

  Starting from Day 1 until disease progression (up to 4 years and 7 months)

• Part B: Progression-free Survival (PFS)

  PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first.

  Starting from Day 1 until disease progression (up to 4 years and 7 months)

• Part B: Duration Of Response (DOR)

  DOR, defined as the time from the first determination of an objective response, was assessed by investigator per Response Evaluation Criteria in Solid Tumors v1.1 until the first documentation of progression or death, whichever occurred first. Results are reported only for arms with responders.

  Starting from Day 1 until disease progression (up to 4 years and 7 months)

• Part B: Disease Control Rate (DCR)

  DCR was defined as the percentage of participants with a best overall response of CR, PR, and stable disease (SD).

  Starting from Day 1 until disease progression (up to 4 years and 7 months)

• Part B: Clinical Benefit Rate (CBR)

  CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks.

  Starting from Day 1 until disease progression (up to 4 years and 7 months)

• Part B: Overall Survival (OS)

  OS was defined as the time from the date of first dose of study drug to death due to any cause.

  From Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)

Secondary Outcomes (17)

• Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab

  Cycle 4 Day 1 (0 hours and 4 hours) post dose

• Part A: Ctrough Of Pamiparib

  Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

• Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib

  Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

• Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib

  Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

• Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib

  Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Study Arms (2)

Part A: Dose Escalation Phase

EXPERIMENTAL

Participants received tislelizumab and pamiparib (dose escalation) until determination of the maximum tolerated dose/recommended Phase 2 dose.

Biological: Tislelizumab; Drug: Pamiparib

Part B: Dose Expansion Phase

EXPERIMENTAL

Participants received tislelizumab and pamiparib (dose expansion).

Biological: Tislelizumab; Drug: Pamiparib

Interventions

Tislelizumab BIOLOGICAL

Also known as: BGB-A317

Part A: Dose Escalation Phase; Part B: Dose Expansion Phase

Pamiparib DRUG

Also known as: BGB-290

Part A: Dose Escalation Phase; Part B: Dose Expansion Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants voluntarily agreed to participate by giving written informed consent.
• Must have received standard of care in the primary treatment of their disease.
• Participants who had the below specified histologically confirmed malignancies that had progressed to the advanced or metastatic stage:
• 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.
• 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.

You may not qualify if:

• Participants with ovarian cancer who have platinum-resistant/refractory disease, defined as progressive disease at the first tumor assessment while receiving platinum-containing chemotherapy.
• Participant had history of severe hypersensitivity reactions to other mAbs.
• Any major surgery within 28 days before first dose of study drugs.
• Prior allogeneic stem cell transplantation or organ transplantation.
• 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).
• Concurrent participation in another clinical trial.
• 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.
• 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.
• Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or PARP.
• 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:
• Controlled Type I diabetes;
• Hypothyroidism managed with no treatment other than with hormone replacement therapy;
• Controlled celiac disease;

Sponsors & Collaborators

• BeiGene: lead
• Myriad Genetic Laboratories, Inc.: collaborator

Study Sites (29)

Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology

Dallas, Texas, 75246, United States

Location

Texas Oncology

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

The Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Mid North Coast Cancer Institute

Coffs Harbour, New South Wales, 2450, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Westmead Hospital

Parramatta, New South Wales, Australia

Location

Prince of Wales

Randwick, New South Wales, Australia

Location

Northern Cancer Institute

St Leonards, New South Wales, 2065, Australia

Location

Icon Cancer Care

Brisbane, Queensland, 4101, Australia

Location

Monash Health

Clayton, Victoria, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Location

Linear Clinical Research Ltd

Nedlands, Western Australia, Australia

Location

Institut Gustave Roussy

Paris, 94800, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Capital and Coast District Health Board

Wellington, 6021, New Zealand

Location

Hospital Universitario Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 31378459 RESULT

• Friedlander M, Mileshkin L, Lombard J, Frentzas S, Gao B, Wilson M, Meniawy T, Baron-Hay S, Briscoe K, McCarthy N, Fountzilas C, Cervantes A, Ge R, Wu J, Spira A. Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. Br J Cancer. 2023 Sep;129(5):797-810. doi: 10.1038/s41416-023-02349-0. Epub 2023 Jul 20.

  PMID: 37474720 DERIVED

MeSH Terms

Interventions

tislelizumab; pamiparib

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2016
• First Posted: January 21, 2016
• Study Start: February 2, 2016
• Primary Completion: September 9, 2020
• Study Completion: September 9, 2020
• Last Updated: December 6, 2021
• Results First Posted: December 6, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

US (12); GB (1); NZ (2); ES (2); FR (2); AU (10)