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
Overview
- Phase
- Phase 1
- Intervention
- Tislelizumab
- Conditions
- Not specified
- Sponsor
- BeiGene
- Enrollment
- 446
- Locations
- 65
- Primary Endpoint
- Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Phase 1 Key Inclusion Criteria
- •Had Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (\<=)
- •Greater than or equal to (\>=) measurable lesion per RECIST v1.
- •Had adequate organ function.
- •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
- •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 was 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.
Exclusion Criteria
- •Active brain or leptomeningeal metastasis.
- •Active autoimmune diseases or history of autoimmune diseases that could have relapsed.
- •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).
- •Concurrent participation in another therapeutic clinical trial.
- •Received prior therapies targeting TIGIT.
- •Phase 1b Key Exclusion Criteria:
- •Participants 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 participants 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).
Arms & Interventions
Phase 1: Dose Verification: Cohort 1B (Ociperlimab 900 mg + Tislelizumab 200 mg)
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.
Intervention: Tislelizumab
Phase 1: Dose Verification: Cohort 1A (Ociperlimab 900 mg)
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.
Intervention: Ociperlimab
Phase 1: Dose Verification: Cohort 1B (Ociperlimab 900 mg + Tislelizumab 200 mg)
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.
Intervention: Ociperlimab
Phase 1: Dose Escalation: Ociperlimab 50 mg + Tislelizumab 200 mg
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.
Intervention: Ociperlimab
Phase 1: Dose Escalation: Ociperlimab 50 mg + Tislelizumab 200 mg
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.
Intervention: Tislelizumab
Phase 1: Dose Escalation: Ociperlimab 150 mg + Tislelizumab 200 mg
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.
Intervention: Ociperlimab
Phase 1: Dose Escalation: Ociperlimab 150 mg + Tislelizumab 200 mg
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.
Intervention: Tislelizumab
Phase 1: Dose Escalation: Ociperlimab 450 mg + Tislelizumab 200 mg
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.
Intervention: Ociperlimab
Phase 1: Dose Escalation: Ociperlimab 450 mg + Tislelizumab 200 mg
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.
Intervention: Tislelizumab
Phase 1: Dose Escalation: Ociperlimab 900 mg + Tislelizumab 200 mg
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.
Intervention: Ociperlimab
Phase 1: Dose Escalation: Ociperlimab 900 mg + Tislelizumab 200 mg
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.
Intervention: Tislelizumab
Phase 1: Dose Escalation: Ociperlimab 1800 mg + Tislelizumab 200 mg
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.
Intervention: Ociperlimab
Phase 1: Dose Escalation: Ociperlimab 1800 mg + Tislelizumab 200 mg
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 1
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 1
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 1
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.
Intervention: Paclitaxel
Phase 1b: Dose Expansion: Cohort 1
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.
Intervention: Nab paclitaxel
Phase 1b: Dose Expansion: Cohort 1
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.
Intervention: Carboplatin
Phase 1b: Dose Expansion: Cohort 2
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 2
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 2
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.
Intervention: Pemetrexed
Phase 1b: Dose Expansion: Cohort 2
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.
Intervention: Carboplatin
Phase 1b: Dose Expansion: Cohort 2
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.
Intervention: Cisplatin
Phase 1b: Dose Expansion: Cohort 3
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 3
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 4
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 4
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 4
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.
Intervention: Carboplatin
Phase 1b: Dose Expansion: Cohort 4
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.
Intervention: Cisplatin
Phase 1b: Dose Expansion: Cohort 4
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.
Intervention: Etoposide
Phase 1b: Dose Expansion: Cohort 5
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 5
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 6
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 6
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 6
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.
Intervention: Paclitaxel
Phase 1b: Dose Expansion: Cohort 6
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.
Intervention: Cisplatin
Phase 1b: Dose Expansion: Cohort 6
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.
Intervention: 5fluorouracil
Phase 1b: Dose Expansion: Cohort 7
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 7
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 7
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.
Intervention: Paclitaxel
Phase 1b: Dose Expansion: Cohort 7
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.
Intervention: Cisplatin
Phase 1b: Dose Expansion: Cohort 7
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.
Intervention: 5fluorouracil
Phase 1b: Dose Expansion: Cohort 8
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 8
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 9
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.
Intervention: Ociperlimab
Phase 1b: Dose Expansion: Cohort 9
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.
Intervention: Tislelizumab
Phase 1b: Dose Expansion: Cohort 9
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.
Intervention: Cisplatin
Phase 1b: Dose Expansion: Cohort 9
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.
Intervention: 5fluorouracil
Phase 1b: Dose Expansion: Cohort 9
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.
Intervention: Oxaliplatin
Phase 1b: Dose Expansion: Cohort 9
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.
Intervention: Capecitabine
Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 450 mg + Tislelizumab 200 mg)
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.
Intervention: Ociperlimab
Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 450 mg + Tislelizumab 200 mg)
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.
Intervention: Tislelizumab
Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 900 mg + Tislelizumab 200 mg)
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.
Intervention: Ociperlimab
Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 900 mg + Tislelizumab 200 mg)
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.
Intervention: Tislelizumab
Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 1800 mg + Tislelizumab 200 mg)
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.
Intervention: Ociperlimab
Phase 1b: Dose Optimization: Cohort 10: (Ociperlimab 1800 mg + Tislelizumab 200 mg)
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.
Intervention: Tislelizumab
Outcomes
Primary Outcomes
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time Frame: Up to 30 days after the last dose of study interventions (up to 35.7 months [Dose escalation cohorts] and up to 13.3 months [Dose verification cohorts])
An AE was defined as any unfavorable and unintended sign, symptom, or disease associated with the use of study drugs, whether considered related to study drugs or not. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly or was considered a medically significant. Treatment-emergent adverse event (TEAE) was an AE that has an onset date or a worsening in severity from baseline on or after the first dose of study drug up to 30 days following study drug discontinuation or initiation of the first new systemic anticancer therapy, whichever occurred first. Severity of AEs was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v.5.0, which consists of: Grade 1 Mild; Grade 2 Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death due to AE.
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Up to 28 days (for Dose escalation cohorts) and up to 21 days (for Dose verification cohorts)
The DLTs were defined as high grade (Grade 3 or 4) non-hematologic toxicities (that is, \>= Grade 4 toxicity; Grade 3 toxicity that is clinically significant and does not resolve to baseline or \<=Grade 1 within 7 days of initiating optimal supportive care), or hematologic toxicities (Grade 4 neutropenia lasting \> 7 days; \>=Grade 3 febrile neutropenia; Grade 3 thrombocytopenia with clinically significant bleeding; Grade 4 thrombocytopenia lasting \> 7 days; \>=Grade 4 anemia occurring during the DLT assessment window and considered by the investigator to be related to ociperlimab and/or tislelizumab.
Phase 1: Maximum Administered Dose (MAD) of Ociperlimab in Combination With Tislelizumab
Time Frame: Up to 28 days (Dose escalation cohort)
MAD was defined as the highest dose of ociperlimab administered.
Phase 1: Recommended Phase 2 Dose (RP2D) of Ociperlimab in Combination With Tislelizumab
Time Frame: up to 28 days (Dose escalation cohorts)
RP2D of Ociperlimab in combination with Tislelizumab 200 mg was determined primarily from the safety, tolerability, and pharmacokinetic (PK) data of dose escalation cohorts.
Phase 1b: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Time Frame: Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)
ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Secondary Outcomes
- Phase 1: ORR as Per RECIST v.1.1(Maximum time duration on study: up to 35.7 months (Dose escalation cohorts) and up to 13.3 months (Dose verification cohorts))
- Phase 1: Duration of Response (DOR) as Per RECIST v.1.1(From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: up to 35.7 months [Dose escalation cohorts] and up to 13.3 months [Dose verification cohorts]))
- Phase 1: Disease Control Rate (DCR) as Per RECIST v.1.1(From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: up to 35.7 months [Dose escalation cohorts] and up to 13.3 months [Dose verification cohorts]))
- Phase 1 (Dose Escalation): Serum Concentrations of Ociperlimab(C1D1 (pre and post dose; 24 hours (h) 72h, 168h and 336 h post-dose), C2D1 (pre- and post-dose), C5D1 (pre and post dose,168h and 336 h post-dose), C6D1 (pre and post-dose), pre-dose on C9D1,C13D1,C17D1,C25D1 (Cycle 1= 28 days; Cycle 2 onwards= 21 days))
- Phase 1 (Dose Escalation): Serum Concentrations of Tislelizumab(Cycle 1, Day 8 (pre-dose), Cycle 1, Day 8 (post-dose), Cycle 2, Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose), Cycle 5 Day 1 (post-dose), pre-dose of Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 25 Day 1 (each cycle = 21 days))
- Phase 1 (Dose Verification): Serum Concentrations of Ociperlimab(Pre-dose, post-dose, 24 h,72 h,168 h,336 h post-dose C1D1, Pre-dose, post-dose on C2D1, Pre-dose, post-dose,168 h, 336 h post-dose on C5D1, Pre-dose, post-dose on C6D1, pre-dose C9D1 and C13D1 (each cycle = 21 days))
- Phase 1 (Dose Verification): Serum Concentrations of Tislelizumab(Cycle 1 Day 1 (pre-dose), Cycle 1 Day 1 (post-dose), Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose), Cycle 5 Day 1 (post-dose), Cycle 6 Day 1 (pre-dose), Cycle 9 Day 1 (pre-dose), Cycle 13 Day 1 (pre-dose) (each cycle = 21 days))
- Phase 1: Number of Participants With Immunogenic Response to Ociperlimab and Tislelizumab(Up to 32.2 months (Dose escalation cohorts) and up to 11 months (Dose verification cohorts))
- Phase 1b: DOR as Per RECIST v.1.1(From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: Up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10]))
- Phase 1b: DCR as Per RECIST v.1.1(From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: Up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10]))
- Phase 1b: Progression Free Survival (PFS) as Per RECIST v.1.1(From first dose of study drugs to the date of the first documentation of PD or death, whichever came first (Maximum time duration on study: up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10]))
- Phase 1b (Cohorts 1-10): Number of Participants With TEAEs and TESAEs(Up to 30 days after the last dose of study interventions (Maximum time duration on study: up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10]))
- Phase 1b (Cohort 1-9): Serum Concentrations of Ociperlimab(Cycle 1 Day 1 (pre-dose), Cycle 1 Day 1 (post-dose), Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose and post-dose), pre-dose on Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1 and Cycle 25 Day 1 (each cycle = 21 days))
- Phase 1b (Cohort 1-9): Serum Concentrations of Tislelizumab(Cycle 1 Day 1 (pre-dose and post-dose), Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose and post-dose), pre-dose on Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1 and Cycle 25 Day 1 (each cycle = 21 days))
- Phase 1b (Cohort 10): Serum Concentrations of Ociperlimab(Pre-dose, post-dose, 168 h, 336 h post-dose Cycle1 Day 1, Pre-dose on Cycle 2 Day 1, Pre-dose, post-dose (30 min) on Cycle 5 Day 1, Pre-dose on Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, and Cycle 25 Day 1 (each cycle = 21 days))
- Phase 1b (Cohort 10): Serum Concentrations of Tislelizumab(Cycle 1 Day 1 (pre-dose and post-dose, Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose and post-dose), pre-dose of Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1 and Cycle 25 Day 1 (each cycle = 21 days))
- Phase 1b (Cohort 1-10): Number of Participants With Immunogenic Response to Ociperlimab and Tislelizumab(Up to 34.4 months (Cohorts 1 to 9) and up to 20.8 months (Cohort 10))
- Phase 1b (Cohort 1-10): Percentage of Participants With ORR: TIGIT Biomarkers Expression(Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10))
- Phase 1b (Cohort 1-10): Percentage of Participants With ORR: PD-L1 Biomarkers Expression(Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10))
- Phase 1b (Cohort 1-10): PFS in TIGIT Biomarkers Expression(Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10))
- Phase 1b (Cohort 1-10): PFS in PD-L1 Biomarkers Expression(Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10))