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

BeiGene

Status and phase: Completed; Phase 1

Conditions: Locally Advanced and Metastatic Solid Tumors

Treatments: Drug: Etoposide; Drug: Capecitabine; Drug: Ociperlimab; Drug: Nab paclitaxel; Drug: Pemetrexed; Drug: Oxaliplatin; Drug: 5fluorouracil; Drug: Paclitaxel; Drug: Cisplatin; Drug: Tislelizumab; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04047862

BGB-900-105

Details and patient eligibility

About

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

Enrollment: 449 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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449 participants in 11 patient groups

Phase 1

Experimental group

Description:

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.

Treatment:

Drug: Ociperlimab

Drug: Tislelizumab

Phase 1b Cohort 1

Experimental group

Description:

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)

Treatment:

Drug: Nab paclitaxel

Drug: Paclitaxel

Drug: Ociperlimab

Drug: Tislelizumab

Drug: Carboplatin

Phase 1b Cohort 2

Experimental group

Description:

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)

Treatment:

Drug: Pemetrexed

Drug: Cisplatin

Drug: Ociperlimab

Drug: Tislelizumab

Drug: Carboplatin

Phase 1b Cohort 3

Experimental group

Description:

Participants with metastatic NSCLC (PD-L1 positive, \[TC\] ≥ 1%) will be treated with ociperlimab + tislelizumab

Treatment:

Drug: Ociperlimab

Drug: Tislelizumab

Phase 1b Cohort 4

Experimental group

Description:

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

Treatment:

Drug: Etoposide

Drug: Cisplatin

Drug: Ociperlimab

Drug: Tislelizumab

Drug: Carboplatin

Phase 1b Cohort 5

Experimental group

Description:

Checkpoint inhibitor (CPI)-experienced NSCLC patients will be treated with ociperlimab plus tislelizumab

Treatment:

Drug: Ociperlimab

Drug: Tislelizumab

Phase1b Cohort 6

Experimental group

Description:

Patients with metastatic ESCC will be treated with ociperlimab + tislelizumab + cisplatin + 5-fluorouracil /paclitaxel Q3W for 6 cycles followed by ociperlamib+tislelizumab Q3W

Treatment:

Drug: 5fluorouracil

Drug: Cisplatin

Drug: Paclitaxel

Drug: Ociperlimab

Drug: Tislelizumab

Phase1b Cohort 7

Experimental group

Description:

Patients with metastatic EAC will be treated with ociperlimab + tislelizumab + cisplatin + 5-fluorouracil or paclitaxel Q3W for 6 cycles followed by ociperlamib+tislelizumab Q3W

Treatment:

Drug: 5fluorouracil

Drug: Cisplatin

Drug: Paclitaxel

Drug: Ociperlimab

Drug: Tislelizumab

Phase1b Cohort 8

Experimental group

Description:

Patients with recurrent or metastatic HNSCC (PD-L1 positive, vCPS≥ 1%) will be treated with ociperlimab + tislelizumab Q3W

Treatment:

Drug: Ociperlimab

Drug: Tislelizumab

Phase1b Cohort 9

Experimental group

Description:

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

Treatment:

Drug: Oxaliplatin

Drug: Capecitabine

Drug: 5fluorouracil

Drug: Cisplatin

Drug: Ociperlimab

Drug: Tislelizumab

Phase 1b Cohort10

Experimental group

Description:

Patients with metastatic NSCLC (PD-L1 positive, \[TC\] ≥ 1%) will be treated with tislelizumab in combination with ociperlimab 450mg, 900mg or 1800mg Q3W.

Treatment:

Drug: Ociperlimab

Drug: Tislelizumab