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 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.

Study Overview

• Status: Completed
• 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): 446
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Cancer and Haematology Centre
    • Camperdown, New South Wales, Australia, 2050
      • Chris Obrien Lifehouse
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Pindara Private Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Foundation
    • Woolloongabba, Queensland, Australia, 4102
      • Metro South Health, Cancer Trials Unit Division of Cancer Services Pah
  • South Australia
    • Windsor Gardens, South Australia, Australia, 5087
      • Ashford Cancer Centre Research Northeast
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Bendigo, Victoria, Australia, 3550
      • Bendigo Health
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research
    • Subiaco, Western Australia, Australia, 6008
      • St John of God Health Care
• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 101149
      • Beijing Luhe Hospital, Capital Medical University
    • 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, 450052
      • The First Affiliated Hospital of Zhengzhou University
    • 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
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • 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
• Korea, Republic of
  • Gyeonggi-do
    • Goyangsi, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
    • Seongnamsi, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Suwonsi, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic University of Korea, St Vincents Hospital
  • Gyeongsangnamdo
    • Jinjusi, Gyeongsangnamdo, Korea, Republic of, 52727
      • Gyeongsang National University Hospital
  • Incheon Gwang'yeogsi
    • Incheon, Incheon Gwang'yeogsi, Korea, Republic of, 21565
      • Gachon University Gil Medical Center
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Severance Hospital Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06591
      • The Catholic University of Korea, Seoul St Marys Hospital
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 07061
      • Smg Snu Boramae Medical Center
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Christchurch, New Zealand, 8011
    • Nzcr Christchurch
• Taiwan
  • Hualien, Taiwan, 970
    • Hualien Tzu Chi Hospital
  • 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, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital
  • Taipei, Taiwan, 231405
    • Taipei Tzu Chi Hospital
  • Taoyuan, Taiwan, 33305
    • Linkou Chang Gung Memorial Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85254
      • Mayo Clinic Phoenix
  • Florida
    • Fort Myers, Florida, United States, 33901
      • SCRI Florida Cancer Specialists South
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Saint Petersburg, Florida, United States, 33705
      • SCRI Florida Cancer Specialists North
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, Pllc Nashville
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

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. 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.

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

19

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	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: 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.	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: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	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: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	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: 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.	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: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	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: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	Drug: Ociperlimab; Administered as an intravenous (IV) injection; Drug: Tislelizumab; Administered as an IV injection
Experimental: 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.	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	Measure Description	Time Frame
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	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.	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])
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)	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.	Up to 28 days (for Dose escalation cohorts) and up to 21 days (for Dose verification cohorts)
Phase 1: Maximum Administered Dose (MAD) of Ociperlimab in Combination With Tislelizumab	MAD was defined as the highest dose of ociperlimab administered.	Up to 28 days (Dose escalation cohort)
Phase 1: Recommended Phase 2 Dose (RP2D) of Ociperlimab in Combination With Tislelizumab	RP2D of Ociperlimab in combination with Tislelizumab 200 mg was determined primarily from the safety, tolerability, and pharmacokinetic (PK) data of dose escalation cohorts.	up to 28 days (Dose escalation cohorts)
Phase 1b: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1	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.	Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: ORR as Per RECIST v.1.1	ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. Per RECIST 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 < 10 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.	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	DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of progression (PD) or death, whichever came first. DOR was estimated using the Kaplan-Meier method. Per RECIST 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 < 10 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. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	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	DCR was defined as the percentage of participants with best overall response (BOR), as per RECIST v.1.1, of a CR, PR, or stable disease (SD). Per RECIST 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 < 10 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	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	Serum concentrations of ociperlimab were measured. Post-dose refers to the data collected for 30 minutes post-infusion. "C" in the timeframe below refers to "Cycle" and D refers to "Day" and "h" refers to "hours".	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	Serum Concentrations of Tislelizumab was determined. Post-dose refers to the data collected for 30 minutes post-infusion.	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	Serum concentration of ociperlimab was determined. Post-dose refers to the data collected for 30 minutes post-infusion. "C" in the timeframe below refers to "Cycle" and D refers to "Day" and "h" refers to "hours".	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	Serum concentrations of tislelizumab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.	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	Immunogenic responses to ociperlimab and tislelizumab included: treatment emergent, treatment-induced and treatment boosted anti-drug antibodies (ADA) and neutralizing antibody (NAb) positive assessments. Treatment-emergent ADA was defined as the sum of treatment-boosted ADA and treatment-induced ADA participants. Treatment-induced ADA was defined as ADA-evaluable participants that were ADA-negative at baseline and ADA-positive after drug administration during the treatment or follow-up observation period. Treatment-boosted ADA was defined as the Baseline-positive ADA-evaluable participants with significant increases (4-fold or higher) in ADA titer after drug administration during the treatment or follow-up observation period. NAb positive was defined as ADA-evaluable participants with positive Nab at any time including baseline and/or after drug administration.	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	DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of progression or death, whichever came first. DOR was estimated using the Kaplan-Meier method. Per RECIST 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 < 10 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. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	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	DCR was defined as the percentage of participants with BOR, as per RECIST v.1.1, of a CR, PR, or SD. 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 < 10 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. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	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	PFS was defined as the time from the date of the first dose of study drugs to the date of the first documentation of PD assessed by the investigator using RECIST v1.1 or death, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	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	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. An 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. 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 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.	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	Serum concentrations of ociperlimab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.	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	Serum concentrations of tislelizumab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.	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	Serum concentrations of ociperlimab were determined. Post-dose refers to the data collected for 30 minutes post-infusion and 'h' in the time-frame section refers to hours.	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	Serum concentrations of tislelizumab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.	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	Immunogenic responses to ociperlimab and tislelizumab included: treatment emergent, treatment-induced and treatment boosted ADA and NAb positive assessments. Treatment-emergent ADA was defined as the sum of treatment-boosted ADA and treatment-induced ADA participants. Treatment-induced ADA was defined as ADA-evaluable participants that were ADA-negative at baseline and ADA-positive after drug administration during the treatment or follow-up observation period. Treatment-boosted ADA was defined as the Baseline-positive ADA-evaluable participants with significant increases (4-fold or higher) in ADA titer after drug administration during the treatment or follow-up observation period. NAb positive was defined as ADA-evaluable participants with positive Nab at any time including baseline and/or after drug administration.	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	Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression. The TIGIT expression on immune cells (IC) and the classification thresholds were different for various cohorts. For Cohort 4, TIGIT IC was categorized as <1% or >=1%; for Cohorts 1, 2, 3, 5, 6, 8, 9 and 10, TIGIT IC was categorized as <5% or >=5%. ORR is reported for each TIGIT subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.	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	Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression. The PD-L1 expression scoring algorithm and the classification thresholds were also different for various cohorts as follows: For Cohort 1 and Cohort 2, PD-L1 TC <1% or >= 1%; for Cohorts 3, 5, and 10, PD-L1 TC < 50% or >=50%; for Cohort 4, PD-L1 tumor area positivity (TAP) <1% or >=1%; for Cohort 9, PD-L1 TAP < 5% or >= 5%; for Cohort 6 and 8, PD-L1 TAP <10% or >=10%. ORR is reported for each PD-L1 subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.	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	Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression. The TIGIT expression on immune cells and the classification thresholds were different for various cohorts. For Cohort 4, TIGIT IC was categorized as <1% or >=1%; for Cohorts 1, 2, 3, 5, 6, 8, 9 and 10, TIGIT IC was categorized as <5% or >=5%. Median PFS (mPFS) is reported for each TIGIT subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.	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	Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression. The PD-L1 expression scoring algorithm and the classification thresholds were also different for various cohorts as follows: For Cohort 1 and Cohort 2, PD-L1 TC <1% or >= 1%; for Cohorts 3, 5, and 10, PD-L1 TC < 50% or >=50%; for Cohort 4, PD-L1 tumor area positivity (TAP) <1% or >=1%; for Cohort 9, PD-L1 TAP < 5% or >= 5%; for Cohort 6 and 8, PD-L1 TAP <10% or >=10%. mPFS is reported for each PD-L1 subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.	Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Frentzas S, Kao S, Gao R, Zheng H, Rizwan A, Budha N, de la Hoz Pedroza L, Tan W, Meniawy T. AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors. J Immunother Cancer. 2023 Oct;11(10):e005829. doi: 10.1136/jitc-2022-005829.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2019
• Primary Completion (Actual): August 7, 2024
• Study Completion (Actual): August 7, 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 (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Tislelizumab; Ociperlimab; BGB-A1217; Anti-TIGIT antibody; anti-PD-1 antibody
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Capecitabine; Oxaliplatin; Albumin-Bound Paclitaxel; Pemetrexed; Tislelizumab; Fluorouracil; Etoposide; Carboplatin; Paclitaxel
• Other Study ID Numbers: BGB-900-105; AdvanTIG-105 (Other Identifier: BeiGene); CTR20202608 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No