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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04047862

AdvanTIG-105 (Other Identifier)

CTR20202608 (Other Identifier)

BGB-900-105

Details and patient eligibility

About

The primary objectives of this study were: 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 was to assess overall response rate (ORR) determined by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1 for patients in each dose-expansion cohort.

Enrollment: 446 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Phase 1 Key Inclusion Criteria

1. Had Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (<=) 1.
2. Greater than or equal to (>=) measurable lesion per RECIST v1.1.
3. Had adequate organ function.
4. Phase 1- Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who had 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 was 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. Were 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 could have relapsed.
3. Had 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. Participants 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 participants 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 participants 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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446 participants in 19 patient groups

Phase 1: Dose Escalation: Ociperlimab 50 mg + Tislelizumab 200 mg

Experimental group

Description:

Participants received ociperlimab 50 milligrams (mg) intravenous (IV) infusion on Day 1 of each cycle (cycle 1= 28 days) and tislelizumab 200 mg IV infusion on Day 8 of Cycle 1. If tolerated, participants received ociperlimab and tislelizumab doses IV on Cycle 2 Day 1 (cycle 2 onwards = 21 days) and thereafter every 21 days (that is, \[i.e.\], every 3 weeks \[Q3W\]) until disease progression, adverse events (AEs), participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1: Dose Escalation: Ociperlimab 150 mg + Tislelizumab 200 mg

Experimental group

Description:

Participants received ociperlimab 150 mg IV infusion on Day 1 of each cycle (cycle 1= 28 days) and tislelizumab 200 mg IV infusion on Day 8 of Cycle 1. If tolerated, participants received ociperlimab and tislelizumab doses IV on Cycle 2 Day 1 (cycle 2 onwards = 21 days) and thereafter every 21 days (i.e. Q3W) until disease progression, intolerable toxicity, or withdrawal of consent.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1: Dose Escalation: Ociperlimab 450 mg + Tislelizumab 200 mg

Experimental group

Description:

Participants received ociperlimab 450 mg IV infusion on Day 1 of each cycle (cycle 1= 28 days) and tislelizumab 200 mg IV infusion on Day 8 of Cycle 1. If tolerated, participants received ociperlimab and tislelizumab doses IV on Cycle 2 Day 1 (cycle 2 onwards = 21 days) and thereafter every 21 days (i.e. Q3W) until disease progression, intolerable toxicity, or withdrawal of consent.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1: Dose Escalation: Ociperlimab 900 mg + Tislelizumab 200 mg

Experimental group

Description:

Participants received ociperlimab 900 mg IV infusion on Day 1 of each cycle (cycle 1= 28 days) and tislelizumab 200 mg IV infusion on Day 8 of Cycle 1. If tolerated, participants received ociperlimab and tislelizumab doses IV on Cycle 2 Day 1 (cycle 2 onwards = 21 days) and thereafter every 21 days (i.e. Q3W) until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1: Dose Escalation: Ociperlimab 1800 mg + Tislelizumab 200 mg

Experimental group

Description:

Participants received ociperlimab 1800 mg IV infusion on Day 1 of each cycle (cycle 1= 28 days) and tislelizumab 200 mg IV infusion on Day 8 of Cycle 1. If tolerated, participants received ociperlimab and tislelizumab doses IV on Cycle 2 Day 1 (cycle 2 onwards = 21 days) and thereafter every 21 days (i.e. Q3W) until disease progression, intolerable toxicity, or withdrawal of consent.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1: Dose Verification: Cohort 1A (Ociperlimab 900 mg)

Experimental group

Description:

Participants received ociperlimab 900 mg as monotherapy IV infusion on Day 1 of each 21-day treatment cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Ociperlimab

Phase 1: Dose Verification: Cohort 1B (Ociperlimab 900 mg + Tislelizumab 200 mg)

Experimental group

Description:

Participants received ociperlimab 900 mg as IV infusion on Day 1 of each 21-day treatment cycle and tislelizumab 200 mg IV infusion once every 21 days (i.e. Q3W) until disease progression, intolerable toxicity, or withdrawal of consent.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 1

Experimental group

Description:

Participants with metastatic squamous non-small cell lung cancer (NSCLC) received treatment with ociperlimab 900 mg IV infusion along with tislelizumab 200 mg IV infusion on Day 1 of each 21-day cycle. Participants also received 4 to 6 cycles of chemotherapy with carboplatin at an area under the curve (AUC) 5 or 6 (Day 1) + paclitaxel 200 or 175 mg/m\^2 (Day 1) or nab paclitaxel 100 mg/m\^2 (Days 1, 8 and 15) Q3W p until disease progression, intolerable toxicity, or withdrawal of consent.

Treatment:

Drug: Tislelizumab

Drug: Nab paclitaxel

Drug: Paclitaxel

Drug: Carboplatin

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 2

Experimental group

Description:

Participants with metastatic non-squamous NSCLC received treatment with ociperlimab 900 mg IV infusion and tislelizumab 200 mg IV infusion on Day 1 of each 21-day cycle. Participants also received cisplatin 75 mg/m\^2 or carboplatin (AUC 5) and pemetrexed 500 mg/m\^2 (on Day 1) Q3W for 4-6 cycles followed by ociperlimab 900 mg + tislelizumab 200 mg + pemetrexed 500 mg/m\^2 on Day 1 Q3W until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Pemetrexed

Drug: Tislelizumab

Drug: Cisplatin

Drug: Carboplatin

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 3

Experimental group

Description:

Participants with metastatic NSCLC (programmed cell death protein-ligand 1 \[PD-L1\] positive, tumor cell \[TC\] \>=1%) were treated with ociperlimab 900 mg IV infusion and tislelizumab 200 mg IV infusion on Day 1 of each 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 4

Experimental group

Description:

Participants with extensive-stage small-cell lung cancer (SCLC) received treatment with ociperlimab 900 mg IV infusion, tislelizumab 200 mg IV infusion. Participants also received 4 cycles of etoposide 100 mg/m\^2 (on Days 1, 2, 3), and cisplatin 75 mg/m\^2 or carboplatin AUC 5 (Day 1) Q3W, followed by ociperlimab 900 mg (Day 1) + tislelizumab 200 mg (Day 1) Q3W until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Etoposide

Drug: Cisplatin

Drug: Carboplatin

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 5

Experimental group

Description:

Checkpoint inhibitor (CPI)-experienced NSCLC participants received treatment with ociperlimab 900 mg IV infusion and tislelizumab 200 mg IV infusions on Day 1 of each 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 6

Experimental group

Description:

Participants with metastatic esophageal squamous cell carcinoma (ESCC) received treatment with 6 cycles of ociperlimab 900 mg (Day 1) IV infusion, tislelizumab 200 mg (Day 1) IV infusion, cisplatin 75 mg/m\^2 (Day 1), and 5-fluorouracil 750-800 mg/m\^2 (5-FU; Day 1 to Day 5) or paclitaxel 200 or 175 mg/m\^2 (Day 1) Q3W followed by ociperlimab 900 mg and tislelizumab 200 mg on Day 1 of every 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Cisplatin

Drug: 5fluorouracil

Drug: Paclitaxel

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 7

Experimental group

Description:

Participants with metastatic esophageal adenocarcinoma (EAC) received treatment with 6 cycles of ociperlimab 900 mg (Day 1) IV infusion, tislelizumab 200 mg (Day 1) IV infusion, cisplatin 75 mg/m\^2 (Day 1), and 5-Fluorouracil 750-800 mg/m\^2 (5-FU; Day 1 to Day 5) or paclitaxel 200 or 175 mg/m\^2 (Day 1) Q3W followed by ociperlimab 900 mg and tislelizumab 200 mg on Day 1 of every 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Cisplatin

Drug: 5fluorouracil

Drug: Paclitaxel

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 8

Experimental group

Description:

Participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC; PD-L1 positive, visually estimated Combined Positive Score \[vCPS\] \>= 1%) received treatment with ociperlimab 900 mg IV infusion and tislelizumab 200 mg IV infusions on Day 1 of every 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1b: Dose Expansion: Cohort 9

Experimental group

Description:

Participants with unresectable, locally advanced, recurrent, or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma received treatment with 6 cycles of ociperlimab 900 mg (Day 1) IV infusion, tislelizumab 200 mg (Day 1) IV infusion, (oxaliplatin 1300 mg/m\^2 \[Day 1\] and capecitabine 1000 mg/m\^2 \[Day 1-14 twice daily\]), or (cisplatin 75 mg/m\^2 \[Day\], and 5-FU 750-800 mg/m\^2 \[Day 1-5\]) Q3W followed by ociperlimab 900 mg (Day 1), tislelizumab 200 mg (Day 1) + capecitabine 1000 mg/m\^2 twice daily (Day 1-14) Q3W until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Cisplatin

Drug: 5fluorouracil

Drug: Oxaliplatin

Drug: Capecitabine

Drug: Ociperlimab

Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 450 mg + Tislelizumab 200 mg)

Experimental group

Description:

articipants with metastatic NSCLC (PD-L1 positive, TC \>= 1%) received treatment with ociperlimab 450 mg IV infusion and tislelizumab 200 mg IV infusion on Day 1 of every 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 900 mg + Tislelizumab 200 mg)

Experimental group

Description:

Participants with metastatic NSCLC (PD-L1 positive, TC \>= 1%) received treatment with ociperlimab 900 mg IV infusion and tislelizumab 200 mg IV infusion on Day 1 of every 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab

Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 1800 mg + Tislelizumab 200 mg)

Experimental group

Description:

Participants with metastatic NSCLC (PD-L1 positive, TC \>= 1%) received treatment with ociperlimab 1800 mg IV infusion and tislelizumab 200 mg IV infusion on Day 1 of every 21-day cycle until disease progression, AEs, participant withdrew consent, lost to follow-up or death, whichever came first.

Treatment:

Drug: Tislelizumab

Drug: Ociperlimab