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Completed

NCT Number: NCT03744468

Study of Surzebiclimab (BGB-A425) and Alcestobart (LBL-007) in Combination With Tislelizumab in Advanced Solid Tumors

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Sydney Southwest Private Hospital, Liverpool, New South Wales, Australia

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About this study

Blocking antibodies targeting programmed cell death protein-1 (PD-1) have achieved remarkable results in the treatment of many types of tumors. However, based upon the rate of primary and secondary resistance to PD-1 blockade, it was apparent that additional immuno-regulatory mechanism(s) underlie tumor immune escape. Indeed, research shows that the T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) pathway cooperates with PD-1 to maximize the suppression of effector tumor infiltrating lymphocytes (TILs) as well as promote resistance to anti-PD-1 therapy. Therefore, TIM-3 represents an ideal target with the potential to significantly improve and/or extend the therapeutic benefit of anti-PD-1 therapy to a greater number of participants.

TIM-3, Lymphocyte activation gene-3 (LAG-3), and PD-1 function as immune checkpoint receptors in the overlapping regulation of immune tolerance and have been shown to be co-overexpressed on the TILs from the participant samples of various solid tumors. Furthermore, emerging clinical data and preclinical data demonstrate co-expression of TIM-3, LAG-3, PD-1 often yield T cells exhausted immunophenotype (i.e., cytokine expression, proliferation etc.). Cancer cells take advantage of PD-1, TIM-3, and LAG-3 in inhibiting immune cells' function, and escape the immune surveillance. Based upon the overlapping expression profiles and immuno-regulatory functions, TIM-3 and LAG-3 mediated adaptive resistance, there was strong scientific rationale that simultaneous targeting of these checkpoint blockers, could potentially increase therapeutic benefit and might help to overcome the resistance arising due to anti-PD-(L)-1 therapy. Hence, this study evaluated the safety and preliminary efficacy of surzebiclimab (anti TIM-3), alcestobart (Anti-LAG-3) in combination with tislelizumab (anti PD-1) in patients with advanced solid tumors.

This was an open-label, multicenter, nonrandomized Phase 1 and Phase 2 clinical trial. Phase 1 determined the recommended phase 2 dose (RP2D) for the combination of surzebiclimab and tislelizumab. Phase 2 safety lead-in determined the RP2D for the combination of surzebiclimab, tislelizumab and/or alcestobart. Phase 2 dose expansion continued to evaluate the safety but also focus on the efficacy of the doublet or triplet treatment combination in select tumor types.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 safety lead-in enrolled participants with histologically/cytologically confirmed advanced/metastatic solid tumors who had previously received standard systemic therapy per local guidelines, unless it was not available, not tolerated or determined not appropriate based on investigators judgement, and had at least 1 evaluable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • The phase 2 dose expansion enrolled participants with recurrent/metastatic HNSCC (Cohorts 1 and 4) and advanced/metastatic NSCLC (Cohorts 2 and 5), with disease progression that occurred >=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.

Treatment and study plan

Surzebiclimab

Drug

Humanized immunoglobulin G1 (IgG1)-variant monoclonal antibody against TIM-3

Other names: BGB-A425

Tislelizumab

Drug

Humanized, IgG4-variant monoclonal antibody against PD-1

Other names: BGB-A317

Alcestobart

Drug

Human anti LAG-3 antibody

Other names: LBL-007

Primary outcomes

  1. Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Time frame: Up to 30 days after last dose of study drug (maximum treatment duration: up to 32.7 months)

    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.

  2. Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Surzebiclimab in Combination With Tislelizumab

    Time frame: Up to 28 days

    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.

  3. Phase 1: Recommended Phase 2 Dose (RP2D) of Surzebiclimab in Combination With Tislelizumab

    Time frame: Up to 28 days

    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.

  4. Phase 2 (Safety Lead-In): Number of Participants With TEAEs and SAEs

    Time frame: Up to 30 days after last dose of study drug (maximum duration of treatment: up to 19.6 months in Cohort A and up to 21.5 months in Cohort B)

    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.

  5. Phase 2 (Safety Lead-In): MTD or MAD of Alcestobart in Combination With Tislelizumab

    Time frame: Up to 21 days

    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.

  6. Phase 2 (Safety Lead-In): MTD or MAD of Alcestobart in Combination With Surzebiclimab and Tislelizumab

    Time frame: Up to 21 days

    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.

  7. Phase 2 (Safety Lead-In): RP2D of Alcestobart in Combination With Surzebiclimab and Tislelizumab

    Time frame: Up to 21 days

    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.

  8. Phase 2 (Dose Expansion): Overall Response Rate (ORR)

    Time frame: Maximum time on study: Cohort 1: up to 31.3 months, Cohort 2: up to 32.0 months, Cohort 4: up to11.3 months, Cohort 5: up to 15.9 months

    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

  1. Phase 1: Overall Response Rate (ORR)

    Time frame: Maximum time on study: up to 57.5 months

    ORR was defined as the percentage of participants who had CR or PR. 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.

  2. Phase 2 (Safety Lead- In): Overall Response Rate (ORR)

    Time frame: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months

    ORR was defined as the percentage of participants who had CR or PR. 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.

  3. Phase 1: Disease Control Rate (DCR)

    Time frame: Maximum time on study: up to 57.5 months

    DCR was defined as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD), per RECIST v.1.1. CR was defined as the 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 progressive disease (PD), taking as reference the smallest sum diameters while on study.

  4. Phase 2 (Safety Lead-In): Disease Control Rate (DCR)

    Time frame: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months

    DCR was defined as the percentage of participants with a BOR of CR, PR, or SD, per RECIST v.1.1. CR was defined as the 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: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  5. Phase 2 (Dose Expansion): Disease Control Rate (DCR)

    Time frame: Maximum time on study: Cohort 1: up to 31.3 months, Cohort 2: up to 32.0 months, Cohort 4: up to 11.3 months, Cohort 5: up to 15.9 months

    DCR was defined as the percentage of participants with a BOR of CR, PR, or SD, per RECIST v.1.1. CR was defined as the 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: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  6. Phase 2 (Dose Expansion): Duration of Response (DOR)

    Time frame: From the first determination of an overall response until PD or death, whichever came first (Maximum time on study [Cohort 1: up to 31.3 months, Cohort 2: up to 32.0 months, Cohort 4: up to 11.3 months, Cohort 5: up to 15.9 months])

    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.

  7. Phase 2 (Dose Expansion): Progression Free Survival (PFS)

    Time frame: Maximum time on study: Cohort 1: up to 31.3 months, Cohort 2: up to 32.0 months, Cohort 4: up to 11.3 months, Cohort 5: up to 15.9 months

    Progression free survival was defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of disease progression assessed by investigator or death, whichever occurred first as determined from investigator derived tumor assessments per RECIST 1.1. 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.

  8. Phase 1: Maximum Observed Plasma Concentration (Cmax) of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI; within 30 minutes), 6 hours, 1, 3, 7, 14, 21, and 28 (cycle 1 only) days after EOI. Cycle 1 was 28 days and Cycle 5 was 21 days.

    The maximum observed plasma concentration of surzebiclimab was measured in Cycle 1 and Cycle 5.

  9. Phase 2 (Dose Expansion): Cmax of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

  10. Phase 1: Minimum Observed Plasma Concentration (Cmin) of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, 21, and 28 (cycle 1 only) days after EOI (Cycle 1 was 28 days; Cycle 2 and thereafter were 21 days)

    Cmin of surzebiclimab was determined.

  11. Phase 2 (Dose Expansion): Cmin of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI

  12. Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, 21, and 28 (cycle 1 only) days after EOI (Cycle 1 was28 days; Cycle 2 and thereafter were 21 days)

  13. Phase 2 (Dose Expansion): Tmax of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

  14. Phase 1: Half-Life (t1/2) of Surzebiclimab

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, 21, and 28 days after EOI (Cycle 1 was 28 days)

  15. Phase 2 (Dose Expansion): T1/2 of Surzebiclimab

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

  16. Phase 1: Area Under Curve From 0 to 21 Days (AUC0-21d) of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (Cycle 1 was 28 days; Cycle 2 and thereafter were 21 days)

  17. Phase 2 (Dose Expansion): AUC0-21d of Surzebiclimab

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle duration= 21 days)

  18. Phase 1: Clearance (CL/F) of Surzebiclimab

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, 21, and 28 days after EOI (Cycle 1 was 28 days)

  19. Phase 2 (Dose Expansion): CL/F of Surzebiclimab

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI

  20. Phase 1: Volume of Distribution (Vz/F) of Surzebiclimab

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, 21, and 28 days after EOI (Cycle 1 was 28 days)

  21. Phase 2 (Dose Expansion): Vz/F of Surzebiclimab

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI

    Vz/F of surzebiclimab was determined.

  22. Phase 2 (Safety Lead-In): Cmax of Alcestobart

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

  23. Phase 2 (Safety Lead-In): Cmin of Alcestobart

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

    Cmin of alcestobart was determined.

  24. Phase 2 (Safety Lead-In): Tmax of Alcestobart

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

  25. Phase 2 (Safety Lead-In): t1/2 of Alcestobart

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

  26. Phase 2 (Safety Lead-In): AUC0-21d of Alcestobart

    Time frame: Cycle 1 Day 1 and Cycle 5 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI (each cycle was 21 days)

  27. Phase 2 (Safety Lead-In): CL/F of Alcestobart

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI

  28. Phase 2 (Safety Lead-In): Vz/F of Alcestobart

    Time frame: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI

  29. Phase 1: Serum Concentrations of Tislelizumab

    Time frame: Pre-dose and EOI (within 30 minutes) on Cycle 1 Day 8 and Cycle 5 Day 1, and pre-dose on Day 1 of Cycles 2, 3, 6, 9, 13, 17, and 25 (Cycle 1 was 28 days, Cycle 2 and thereafter were 21 days)

    Serum concentrations of tislelizumab were measured using an enzyme-linked immunosorbent assay (ELISA).

  30. Phase 2 (Dose Expansion): Serum Concentrations of Tislelizumab

    Time frame: Pre-dose on Day 1 of Cycles 1, 2, 5, 6, 9, 13, 17, 25 and at EOI (within 30 minutes) on Day 1 of Cycles 1 and 5 (each cycle was 21 days)

    Serum concentrations of tislelizumab were measured using an enzyme-linked immunosorbent assay (ELISA).

  31. Phase 1: Number of Participants With Anti-Drug Antibodies (ADA) to Surzebiclimab

    Time frame: Maximum time on study: up to 57.5 months

    Immunogenic responses to surzebiclimab 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.

  32. Phase 2 (Safety Lead-In) Cohort B: Number of Participants With Anti-Drug Antibodies to Surzebiclimab

    Time frame: Maximum time on study in Cohort B: up to 21.5 months

    Immunogenic responses to surzebiclimab 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.

  33. Phase 2 (Dose Expansion): Number of Participants With Anti-Drug Antibodies to Surzebiclimab

    Time frame: Maximum time on study: Cohort 1: up to 31.3 months, Cohort 2: up to 32.0 months, Cohort 4: up to 11.3 months, Cohort 5: up to 15.9 months

    Immunogenic responses to surzebiclimab 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.

  34. Phase 2 (Safety Lead-In): Number of Participants With Anti-Drug Antibodies to Alcestobart

    Time frame: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months

    Immunogenic responses to alcestobart 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.

  35. Phase 2 (Dose Expansion) Cohorts 4 and 5: Number of Participants With Anti-Drug Antibodies to Alcestobart

    Time frame: Maximum time on study: Cohort 4: up to 11.3 months, Cohort 5: up to 15.9 months

    Immunogenic responses to alcestobart 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.

  36. Phase 1: Number of Participants With Anti-Drug Antibodies to Tislelizumab

    Time frame: Maximum time on study: up to 57.5 months

    Immunogenic responses to 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.

  37. Phase 2 (Safety Lead-In): Number of Participants With Anti-Drug Antibodies to Tislelizumab

    Time frame: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months

    Immunogenic responses to alcestobart 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.

  38. Phase 2 (Dose Expansion): Number of Participants With Anti-Drug Antibodies to Tislelizumab

    Time frame: Maximum time on study: Cohort 1: up to 31.3 months, Cohort 2: up to 32.0 months, Cohort 4: up to 11.3 months, Cohort 5: up to 15.9 months

    Immunogenic responses to 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.

  39. Phase 2 (Dose Expansion): Number of Participants With TEAEs and SAEs

    Time frame: Up to 30 days after last dose of study drug (maximum treatment duration: Cohort 1: up to 6.9 months, Cohort 2: up to 23.5 months, Cohort 4: up to 9.6 months, Cohort 5: up to 15.4 months)

    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.

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study title

Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Various Combinations of BGB-A425 and LBL-007 With Tislelizumab in Patients With Advanced Solid Tumors

Important dates

Study start
2018
Primary completion
2025
Study completion
2025
First posted
Nov 16, 2018
Registry last updated
Apr 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.