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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Locally Advanced and Metastatic Solid Tumors

Intervention / Treatment
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* Drug: Ociperlimab
* Drug: Tislelizumab
* Drug: Pemetrexed
* Drug: Paclitaxel
* Drug: Nab paclitaxel
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Etoposide
* Drug: 5fluorouracil
* Drug: Oxaliplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Phase 1 Key Inclusion Criteria Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1. ≥ 1 measurable lesion per RECIST v1.1. Has adequate organ function. 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 Signed informed consent form (ICF) and able to comply with study requirements. Age ≥ 18 years (or the legal age of consent) at the time the ICF is signed. 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. ECOG Performance Status ≤ 1 Adequate organ function Willing to use highly effective method of birth control Phase 1 Key Exclusion Criteria: Active brain or leptomeningeal metastasis. Active autoimmune diseases or history of autoimmune diseases that may relapse. 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). Concurrent participation in another therapeutic clinical trial. Received prior therapies targeting TIGIT. Phase 1b Key Exclusion Criteria: Patients with any prior therapy for recurrent/metastatic disease. Non-squamous NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion. Gastric cancer patients with squamous or with positive HER2 expression. Prior therapy with any drug specifically targeting T-cell co-stimulation or checkpoint pathways. (anti-PD(L)1 exception for Cohort 5). Active leptomeningeal disease or uncontrolled brain metastasis. Active autoimmune diseases or history of autoimmune diseases that may relapse. 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). Concurrent participation in another therapeutic clinical study. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>|
| Experimental: Phase 1b Cohort 1<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>Drug: Paclitaxel<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Nab paclitaxel<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Carboplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>|
| Experimental: Phase 1b Cohort 2<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>Drug: Pemetrexed<br>* Administered in accordance with local guidelines, prescribing information/summary of product<br>Drug: Carboplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Cisplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>|
| Experimental: Phase 1b Cohort 3<br>Participants with metastatic NSCLC (PD-L1 positive, [TC] ≥ 1%) will be treated with ociperlimab + tislelizumab | Drug: Ociperlimab<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>|
| Experimental: Phase 1b Cohort 4<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>Drug: Carboplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Cisplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Etoposide<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>|
| Experimental: Phase 1b Cohort 5<br>Checkpoint inhibitor (CPI)-experienced NSCLC patients will be treated with ociperlimab plus tislelizumab | Drug: Ociperlimab<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>|
| Experimental: Phase1b Cohort 6<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>Drug: Paclitaxel<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Cisplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: 5fluorouracil<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>|
| Experimental: Phase1b Cohort 7<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>Drug: Paclitaxel<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Cisplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: 5fluorouracil<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>|
| Experimental: Phase1b Cohort 8<br>Patients with recurrent or metastatic HNSCC (PD-L1 positive, vCPS≥ 1%) will be treated with ociperlimab + tislelizumab Q3W | Drug: Ociperlimab<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>|
| Experimental: Phase1b Cohort 9<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>Drug: Cisplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: 5fluorouracil<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Oxaliplatin<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>Drug: Capecitabine<br>* Administered in accordance with local guidelines , prescribing information/summary of product<br>|
| Experimental: Phase 1b Cohort10<br>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<br>* Administered as an intravenous (IV) injection<br>Drug: Tislelizumab<br>* Administered as an IV injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BGB-A1217, Anti-TIGIT antibody, Tislelizumab, anti-PD-1, Ociperlimab