Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03744468 | Study of Surzebiclimab (BGB-A425) and Alcestobart (LBL-007) in Combination With Tislelizumab in Advanced Solid Tumors | PHASE1 | COMPLETED | 147 | — | — | Nov 13, 2018 | Feb 6, 2025 | Apr 2, 2026 | 40 | United States, Australia +4 |
An Adverse Event (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. 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. 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. 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.
The MAD was defined as the highest dose administered, where all dose levels were tolerated during dose escalation. The MTD was not reached in Phase 1, therefore the MAD was reported.
The RP2D or recommended dose for expansion of the combination treatment was determined based upon the MTD or MAD, and also considered the long-term tolerability, PK, efficacy, and any other relevant data as available.
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. 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. 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. 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.
The MAD was defined as the highest dose administered, where all dose levels were tolerated during dose escalation. The MTD was not reached in Phase 2, therefore the MAD was reported.
The MAD was defined as the highest dose administered, where all dose levels were tolerated during dose escalation. The MTD was not reached in Phase 2, therefore the MAD was reported.
The RP2D or recommended dose for expansion of the combination treatment was determined based upon the MTD or MAD, and also considered the long-term tolerability, PK, efficacy, and any other relevant data as available.
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.
| Arm | Type | Description |
|---|---|---|
| Phase 1 (Dose Escalation): Surzebiclimab 2 Milligrams (mg) + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 2 mg intravenous (IV) infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 2 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 6 mg + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 6 mg IV infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 6 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 20 mg + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 20 mg IV infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 20 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 60 mg + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 60 mg IV infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 60 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 200 mg + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 200 mg IV infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 200 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 400 mg + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 400 mg IV infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 400 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter, until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 800 mg + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 800 mg IV infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 800 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 1600 mg + Tislelizumab | EXPERIMENTAL | Participants received surzebiclimab 1600 mg IV infusion on day 1 of each cycle. In the first cycle, tislelizumab 200 mg was administered intravenously on Day 8. If tolerated, participants received surzebiclimab 400 mg along with tislelizumab sequentially on Day 29 and every 21 days (i.e., once every 21 days) thereafter until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Cycle 1 consisted of 28 days, and each cycle from Cycle 2 onwards consisted of 21 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 60 mg | EXPERIMENTAL | Participants received one dose of surzebiclimab 60 mg IV infusion on Day 1 of Cycle 1 and discontinued the study treatment. Cycle 1 consisted of 28 days. |
| Phase 1 (Dose Escalation): Surzebiclimab 1600 mg | EXPERIMENTAL | Participants received one dose of surzebiclimab 1600 mg IV infusion on Day 1 of Cycle 1 and discontinued the study treatment. Cycle 1 consisted of 28 days. |
| Phase 2 (Safety Lead-In): Cohort A: Alcestobart 300 mg + Tislelizumab | EXPERIMENTAL | Participants received alcestobart 300 mg IV infusion on day 1 of each cycle along with tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Safety Lead-In): Cohort A: Alcestobart 600 mg + Tislelizumab | EXPERIMENTAL | Participants received alcestobart 600 mg IV infusion on day 1 of each cycle along with tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Safety Lead-In): Cohort A: Alcestobart 1200 mg + Tislelizumab | EXPERIMENTAL | Participants received alcestobart 1200 mg IV infusion on day 1 of each cycle along with tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Safety Lead-In): Cohort B: Alcestobart 300 mg + BGB-A425 + Tislelizumab | EXPERIMENTAL | Participants received alcestobart 300 mg IV infusion on day 1 of each cycle along with surzebiclimab 600 mg IV and tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Safety Lead-In): Cohort B: Alcestobart 600 mg + Surzebiclimab + Tislelizumab | EXPERIMENTAL | Participants received alcestobart 600 mg IV infusion on day 1 of each cycle along with surzebiclimab 600 mg IV and tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Safety Lead-In): Cohort B: Alcestobart 900 mg + Surzebiclimab + Tislelizumab | EXPERIMENTAL | Participants received alcestobart 900 mg IV infusion on day 1 of each cycle along with surzebiclimab 600 mg IV and tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Dose Expansion): Cohort 1: HNSCC: Surzebiclimab 600 mg + Tislelizumab | EXPERIMENTAL | Participants with head and neck squamous cell carcinoma (HNSCC) received surzebiclimab 600 mg IV infusion on day 1 of each cycle along with tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Dose Expansion): Cohort 2: NSCLC: Surzebiclimab 600 mg + Tislelizumab | EXPERIMENTAL | Participants with non-small cell lung cancer (NSCLC) received surzebiclimab 600 mg IV infusion on day 1 of each cycle along with tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Dose Expansion): Cohort 4: HNSCC Surzebiclimab 600 mg + Alcestobart 600 mg + Tislelizumab | EXPERIMENTAL | Participants with HNSCC received surzebiclimab 600 mg IV infusion on day 1 of each cycle along with alcestobart 600 mg IV and tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Phase 2 (Dose Expansion): Cohort 5: NSCLC: Surzebiclimab 600 mg + Alcestobart 600 mg + Tislelizumab | EXPERIMENTAL | Participants with NSCLC received surzebiclimab 600 mg IV infusion on day 1 of each cycle along with alcestobart 600 mg IV and tislelizumab 200 mg IV once every 21 days until they were no longer considered to receive clinical benefit, unacceptable toxicity, or withdrawal of informed consent. Each cycle consisted of 21 days. |
| Name | Type | Description |
|---|---|---|
| Surzebiclimab | DRUG | Humanized immunoglobulin G1 (IgG1)-variant monoclonal antibody against TIM-3 |
| Tislelizumab | DRUG | Humanized, IgG4-variant monoclonal antibody against PD-1 |
| Alcestobart | DRUG | Human anti LAG-3 antibody |
Key Inclusion Criteria: * Participants were aged \>=18 years. * Adequate organ function. * Eastern Cooperative Oncology Group (ECOG) performance status \<=1. * Must have been able to provide a recently obtained archival tumor tissue or fresh tumor biopsy. * The phase 1 dose escalation and phase 2 s...