Study of Ociperlimab (BGB-A1217) in Combination With Tislelizumab in Advanced Solid Tumors

Phase 1/1b Study Investigating Safety, Tolerability, PK and Antitumor Activity of Anti-TIGIT Monoclonal Antibody BGB-A1217 in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

The primary objectives of this study are : to assess the safety and tolerability, to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and to determine the recommended Phase 2 dose (RP2D) of BGB-A1217 (known as Ociperlimab) in combination with tislelizumab in participants with advanced solid tumors in phase 1.

Primary objective of Phase 1b is to assess overall response rate (ORR) determined by Investigator per RECIST v1.1 for patients in each dose- expansion cohort

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced and Metastatic Solid Tumors
• Intervention / Treatment: Drug: Ociperlimab; Drug: Tislelizumab; Drug: Paclitaxel; Drug: Nab paclitaxel; Drug: Carboplatin; Drug: Pemetrexed; Drug: Cisplatin; Drug: Etoposide; Drug: 5fluorouracil; Drug: Oxaliplatin; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1-877-828-5568; Email: clinicaltrials@beigene.com

Study Locations

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital
• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100010
      • Beijing Tongren Hospital, CMU
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian cancer hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Cancer Hospital
  • Shaanxi
    • Xian, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xian Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Sichuan Cancer Hospital and Institute
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40201
    • Chung Shan Medical University Hospital
  • Taichung, Taiwan, 40705
    • Veterans General Hospital Taichung
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital
  • Taipei, Taiwan, 231405
    • Taipei Tzu Chi Hospital
  • Taoyuan, Taiwan, 33305
    • Linkou Chang Gung Memorial Hospital
• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Phase 1 Key Inclusion Criteria

1. Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
2. ≥ 1 measurable lesion per RECIST v1.1.
3. Has adequate organ function.
4. phase 1- Patients with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for which treatment is not available, not tolerated or refused.

Phase 1b Key Inclusion Criteria

1. Signed informed consent form (ICF) and able to comply with study requirements.
2. Age ≥ 18 years (or the legal age of consent) at the time the ICF is signed.

3. Histologically or cytologically confirmed tumor types in the following disease cohorts:

   Cohort 1: stage IV squamous NSCLC Cohort 2: stage IV non-squamous NSCLC Cohort 3: stage IV squamous or non-squamous NSCLC with PD-L1 positive. Cohort 4: extensive-stage SCLC Cohort 5: stage IIIB, IIIC or IV NSCLC Cohort 6: stage IV ESCC Cohort 7: stage IV EAC Cohort 8: recurrent or metastatic HNSCC incurable by local therapies Cohort 9: stage IV G/GEJ adenocarcinoma. Cohort 10: stage IV squamous or non-squamous NSCLC with PD-L1 positive.

4. ECOG Performance Status ≤ 1
5. Adequate organ function
6. Willing to use highly effective method of birth control

Phase 1 Key Exclusion Criteria:

1. Active brain or leptomeningeal metastasis.
2. Active autoimmune diseases or history of autoimmune diseases that may relapse.
3. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
4. Concurrent participation in another therapeutic clinical trial.
5. Received prior therapies targeting TIGIT.

Phase 1b Key Exclusion Criteria:

1. Patients with any prior therapy for recurrent/metastatic disease.
2. Non-squamous NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion.
3. Gastric cancer patients with squamous or with positive HER2 expression.
4. Prior therapy with any drug specifically targeting T-cell co-stimulation or checkpoint pathways. (anti-PD(L)1 exception for Cohort 5).
5. Active leptomeningeal disease or uncontrolled brain metastasis.
6. Active autoimmune diseases or history of autoimmune diseases that may relapse.
7. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
8. Concurrent participation in another therapeutic clinical study.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; Cycle 1 (28 Days): A flat dose of ociperlimab as a single agent on Day 1. In the first cycle, 200 mg tislelizumab will be administered on Day 8. If ociperlamib is tolerated in Cycle 1, participants will receive tislelizumab + ociperlimab sequentially on Day 29 and every 21 days for up to 8 months.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: Phase 1b Cohort 1; Participants with metastatic squamous NSCLC will receive ociperlamib + tislelizumab + paclitaxel/nab-paclitaxel + Carbo once every 3 weeks (Q3W) for 4 to 6 cycles (21 days each) followed by ociperlimab + tislelizumab Q3W)	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection; Drug: Paclitaxel; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Nab paclitaxel; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Carboplatin; Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort 2; Participants with metastatic squamous NSCLC will receive ociperlimab + tislelizumab + pemetrexed + Cis/Carbo Q3W for 4 to 6 cycles (21 days each) followed by ociperlamib+tislelizumab Q3W)	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection; Drug: Carboplatin; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Pemetrexed; Administered in accordance with local guidelines, prescribing information/summary of product; Drug: Cisplatin; Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort 3; Participants with metastatic NSCLC (PD-L1 positive, [TC] ≥ 1%) will be treated with ociperlimab + tislelizumab	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: Phase 1b Cohort 4; Patients with extensive stage SCLC will be treated with ociperlimab + tislelizumab + etoposide + Cis/Carbo Q3W for up to 6 to 8 cycles followed by ociperlamib+tislelizumab Q3W	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection; Drug: Carboplatin; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Cisplatin; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Etoposide; Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort 5; Checkpoint inhibitor (CPI)-experienced NSCLC patients will be treated with ociperlimab plus tislelizumab	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: Phase1b Cohort 6; Patients with metastatic ESCC will be treated with ociperlimab + tislelizumab + cisplatin + 5-fluorouracil /paclitaxel Q3W for 6 cycles followed by ociperlamib+tislelizumab Q3W	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection; Drug: Paclitaxel; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Cisplatin; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: 5fluorouracil; Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase1b Cohort 7; Patients with metastatic EAC will be treated with ociperlimab + tislelizumab + cisplatin + 5-fluorouracil or paclitaxel Q3W for 6 cycles followed by ociperlamib+tislelizumab Q3W	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection; Drug: Paclitaxel; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Cisplatin; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: 5fluorouracil; Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase1b Cohort 8; Patients with recurrent or metastatic HNSCC (PD-L1 positive, vCPS≥ 1%) will be treated with ociperlimab + tislelizumab Q3W	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: Phase1b Cohort 9; Patients with metastatic G/GEJ carcinoma will be treated with ociperlimab + tislelizumab + [oxalipatin + capecitabine] or [cisplatin + 5-fluorouracil] Q3W for 6 cycles followed by ociperlamib+tislelizumab + capecitabine Q3W	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection; Drug: Cisplatin; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: 5fluorouracil; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Oxaliplatin; Administered in accordance with local guidelines , prescribing information/summary of product; Drug: Capecitabine; Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort10; Patients with metastatic NSCLC (PD-L1 positive, [TC] ≥ 1%) will be treated with tislelizumab in combination with ociperlimab 450mg, 900mg or 1800mg Q3W.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 1 Dose Escalation - Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)	Up to 28 Days in Cycle 1
Phase 1 Dose Escalation - Number of participants experiencing Serious Adverse Events (SAEs)	Up to 1.5 years
Phase 1 Dose Escalation - Recommended Phase Ib dose (RP2D) of ociperlimab in combination with tislelizumab	Up to 1.5 years
Phase 1b Dose Confirmation - Anti-tumor activity of ociperlimab in combination with tislelizumab in patients with select advanced solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using RECIST v. 1.1.	Up to 1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	Duration of response (DOR) will be determined from investigator derived tumor assessments per RECIST v. 1.1.	Up to 3 years
Disease control rate (DCR)	Disease control rate (DCR) will be determined from investigator derived tumor assessments per RECIST v. 1.1.	Up to 3 years
Progression free survival	Progression free survival will be determined from investigator derived tumor assessments per RECIST 1.1.	Up to 3 years
Immunogenicity as assessed by the presence of anti-drug antibodies		Up to 3 years

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2019
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: August 1, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Tislelizumab; anti-PD-1; Ociperlimab; BGB-A1217; Anti-TIGIT antibody
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Etoposide; Paclitaxel; Fluorouracil; Capecitabine; Oxaliplatin; Albumin-Bound Paclitaxel; Pemetrexed; Tislelizumab
• Other Study ID Numbers: BGB-900-105; AdvanTIG-105 (Other Identifier: BeiGene)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No