Phase 2
N=147
Study of Surzebiclimab (BGB-A425) and Alcestobart (LBL-007) in Combination With Tislelizumab in Advanced Solid Tumors
Locally Advanced or Metastatic Solid Tumors for Phase 1, Dose Escalation and Phase 2 Safety Lead-in · HNSCC for Phase 2 Dose Expansion · NSCLC for Phase 2 Dose Expansion
Bottom Line
View on ClinicalTrials.gov: NCT03744468 ↗Enrolled (actual)
147
Serious AEs
44.2%
Results posted
Apr 2026
Primary outcome: Primary: Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 1; 1; 3; 5 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Surzebiclimab (Drug); Tislelizumab (Drug); Alcestobart (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- BeiGene
- Primary completion
- Feb 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
1; 1; 3; 5; 7; 4 | — |
| PRIMARY Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Surzebiclimab in Combination With Tislelizumab |
1600 | — |
| PRIMARY Phase 1: Recommended Phase 2 Dose (RP2D) of Surzebiclimab in Combination With Tislelizumab |
600 | — |
| PRIMARY Phase 2 (Safety Lead-In): Number of Participants With TEAEs and SAEs |
4; 6; 6; 3; 5; 6 | — |
| PRIMARY Phase 2 (Safety Lead-In): MTD or MAD of Alcestobart in Combination With Tislelizumab |
1200 | — |
| PRIMARY Phase 2 (Safety Lead-In): MTD or MAD of Alcestobart in Combination With Surzebiclimab and Tislelizumab |
900 | — |
| PRIMARY Phase 2 (Safety Lead-In): RP2D of Alcestobart in Combination With Surzebiclimab and Tislelizumab |
600 | — |
| PRIMARY Phase 2 (Dose Expansion): Overall Response Rate (ORR) |
4.8; 9.1; 0.0; 10.5 | — |
| SECONDARY Phase 1: Overall Response Rate (ORR) |
0.0; 0.0; 0.0; 0.0; 0.0; 25.0 | — |
| SECONDARY Phase 2 (Safety Lead- In): Overall Response Rate (ORR) |
0.0; 33.3; 0.0; 0.0; 0.0; 16.7 | — |
| SECONDARY Phase 1: Disease Control Rate (DCR) |
0.0; 0.0; 66.7; 40.0; 66.7; 50.0 | — |
| SECONDARY Phase 2 (Safety Lead-In): Disease Control Rate (DCR) |
50.0; 83.3; 50.0; 100.0; 50.0; 50.0 | — |
| SECONDARY Phase 2 (Dose Expansion): Disease Control Rate (DCR) |
42.9; 45.5; 45.0; 73.7 | — |
| SECONDARY Phase 2 (Dose Expansion): Duration of Response (DOR) |
4.0; 6.9; NA | — |
| SECONDARY Phase 2 (Dose Expansion): Progression Free Survival (PFS) |
1.4; 1.7; 1.9; 4.0 | — |
| SECONDARY Phase 1: Maximum Observed Plasma Concentration (Cmax) of Surzebiclimab |
0.89; 5.48; 17.43; 66.50; 145.09; 244.03 | — |
| SECONDARY Phase 2 (Dose Expansion): Cmax of Surzebiclimab |
182.24; 165.62; 288.43 | — |
| SECONDARY Phase 1: Minimum Observed Plasma Concentration (Cmin) of Surzebiclimab |
1.80; 14.55; 27.84; 62.46; 167.44; 0.47 | — |
| SECONDARY Phase 2 (Dose Expansion): Cmin of Surzebiclimab |
40.24; 32.27; 116.05; 87.92 | — |
| SECONDARY Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Surzebiclimab |
1.30; 1.33; 1.15; 1.20; 1.15; 1.10 | — |
| SECONDARY Phase 2 (Dose Expansion): Tmax of Surzebiclimab |
4.54; 4.00; 2.78 | — |
| SECONDARY Phase 1: Half-Life (t1/2) of Surzebiclimab |
122.20; 203.43; 276.06; 344.59; 356.26; 643.02 | — |
| SECONDARY Phase 2 (Dose Expansion): T1/2 of Surzebiclimab |
325.65; 274.83 | — |
| SECONDARY Phase 1: Area Under Curve From 0 to 21 Days (AUC0-21d) of Surzebiclimab |
727.11; 2734.25; 12911.99; 25213.19; 50478.81; 153224.06 | — |
| SECONDARY Phase 2 (Dose Expansion): AUC0-21d of Surzebiclimab |
37538.32; 31104.68; 90437.84; 66659.54 | — |
| SECONDARY Phase 1: Clearance (CL/F) of Surzebiclimab |
0.03; 0.02; 0.01; 0.01; 0.01; 0.00 | — |
| SECONDARY Phase 2 (Dose Expansion): CL/F of Surzebiclimab |
0.01; 0.01 | — |
| SECONDARY Phase 1: Volume of Distribution (Vz/F) of Surzebiclimab |
4.43; 5.04; 4.48; 5.55; 5.56; 4.38 | — |
| SECONDARY Phase 2 (Dose Expansion): Vz/F of Surzebiclimab |
4.98; 5.69 | — |
| SECONDARY Phase 2 (Safety Lead-In): Cmax of Alcestobart |
61.21; 112.96; 242.51; 61.39; 115.74; 149.57 | — |
| SECONDARY Phase 2 (Safety Lead-In): Cmin of Alcestobart |
2.01; 24.07; 35.38; 9.32; 12.81; 26.44 | — |
| SECONDARY Phase 2 (Safety Lead-In): Tmax of Alcestobart |
1.48; 2.84; 1.54; 1.42; 1.29; 1.28 | — |
| SECONDARY Phase 2 (Safety Lead-In): t1/2 of Alcestobart |
143.35; 248.79; 227.76; 230.84; 200.74; 262.83 | — |
| SECONDARY Phase 2 (Safety Lead-In): AUC0-21d of Alcestobart |
8620.04; 21120.06; 41874.14; 10947.98; 18655.37; 30906.45 | — |
| SECONDARY Phase 2 (Safety Lead-In): CL/F of Alcestobart |
0.03; 0.02; 0.02; 0.02; 0.03; 0.02 | — |
| SECONDARY Phase 2 (Safety Lead-In): Vz/F of Alcestobart |
5.48; 7.83; 7.29; 6.40; 7.59; 7.81 | — |
| SECONDARY Phase 1: Serum Concentrations of Tislelizumab |
0.68; 2.70; 40.50; 51.10; 57.91; 54.87 | — |
| SECONDARY Phase 2 (Dose Expansion): Serum Concentrations of Tislelizumab |
9.09; 10.61; 26.45; 13.57; 62.51; 77.36 | — |
| SECONDARY Phase 1: Number of Participants With Anti-Drug Antibodies (ADA) to Surzebiclimab |
0; 0; 1; 1; 1; 0 | — |
| SECONDARY Phase 2 (Safety Lead-In) Cohort B: Number of Participants With Anti-Drug Antibodies to Surzebiclimab |
0; 1; 0; 0; 1; 0 | — |
| SECONDARY Phase 2 (Dose Expansion): Number of Participants With Anti-Drug Antibodies to Surzebiclimab |
2; 4; 0; 1; 2; 4 | — |
| SECONDARY Phase 2 (Safety Lead-In): Number of Participants With Anti-Drug Antibodies to Alcestobart |
2; 0; 0; 0; 1; 0 | — |
| SECONDARY Phase 2 (Dose Expansion) Cohorts 4 and 5: Number of Participants With Anti-Drug Antibodies to Alcestobart |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Phase 1: Number of Participants With Anti-Drug Antibodies to Tislelizumab |
0; 1; 1; 0; 1; 2 | — |
| SECONDARY Phase 2 (Safety Lead-In): Number of Participants With Anti-Drug Antibodies to Tislelizumab |
3; 1; 0; 0; 3; 1 | — |
| SECONDARY Phase 2 (Dose Expansion): Number of Participants With Anti-Drug Antibodies to Tislelizumab |
7; 10; 5; 4; 7; 9 | — |
| SECONDARY Phase 2 (Dose Expansion): Number of Participants With TEAEs and SAEs |
20; 21; 20; 20; 11; 11 | — |
Summary
This was an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of surzebiclimab (BGB-A425) and/or alcestobart (LBL-007) with tislelizumab.
Eligibility Criteria
Key Inclusion Criteria
- Participants were aged >=18 years.
- Adequate organ function.
- Eastern Cooperative Oncology Group (ECOG) performance status =10 weeks from the initiation of anti-PD-1/PD-L1 treatment for locally advanced or metastatic disease and had at least 1 measurable lesion outside of the central nervous system per RECIST v1.1.
Key Exclusion Criteria
- A history of severe hypersensitivity reactions to other monoclonal antibodies.
- Active autoimmune disease or a history of autoimmune diseases that might relapse or a history of life-threatening toxicity related to prior immune therapy.
- Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication <=14 days before administration of study drug.
- A history of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases.
- Prior therapy targeting TIM-3 and/or LAG-3.
- The phase 2 dose expansion NSCLC cohorts excluded participants with known sensitizing epidermal growth factor receptor (EGFR) mutation, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, anaplastic lymphoma kinase (ALK) fusion, or c-ros oncogene 1 (ROS1) fusion.
NOTE: Other protocol defined Inclusion/Exclusion criteria might apply.
Data sourced from ClinicalTrials.gov (NCT03744468). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.