Locally Advanced or Metastatic Solid Tumors for Phase 1, Dose Escalation and Phase 2 Safety Lead-inPhase 1/2NCT03744468
Study of Surzebiclimab (BGB-A425) and Alcestobart (LBL-007) in Combination With Tislelizumab in Advanced Solid Tumors
A Phase 1/2 study testing Surzebiclimab, Tislelizumab and Alcestobart in people with Locally Advanced or Metastatic Solid Tumors for Phase 1, Dose Escalation and Phase 2 Safety Lead-in and HNSCC for Phase 2 Dose Expansion, run by BeiGene at 40 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 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
- What is being tested?
- Surzebiclimab, Tislelizumab and Alcestobart
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 147 participants
- Where
- 40 sitesin 6 countries
- Study dates
- 13 Nov 2018to 6 Feb 2025
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
40 sites in 6 countries.
40 sites in 6 countries
United States11 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045-2517
University of North Carolina At Chapel Hill
Chapel Hill, North Carolina, 27514-4220
University of Virginia
Charlottesville, Virginia, 22908-0817
University of Chicago Medical Center
Chicago, Illinois, 60637-1443
Schar Cancer Institute
Fairfax, Virginia, 22031-4867
The University of Texas Md Anderson Cancer Center
Houston, Texas, 77030-4009
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536-7001
Weill Cornell Medical College Newyork Presbyterian Hospital
New York, New York, 10065-4870
Chao Family Comprehensive Cancer Center
Orange, California, 92868-3201
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2434
Ut Health San Antonio Mays Cancer Center
San Antonio, Texas, 78229-4427
Australia11 sites
Sunshine Coast Hospital and Health Service
Birtinya, Queensland, QLD 4575
Box Hill Hospital
Box Hill, Victoria, VIC 3128
Lyell McEwin Hospital
Elizabeth Vale, South Australia, SA 5112
Sydney Southwest Private Hospital
Liverpool, New South Wales, NSW 2170
Cabrini Research and Education Institute
Malvern, Victoria, VIC 3144
Peter Maccallum Cancer Centre
Melbourne, Victoria, VIC 3000
Hollywood Private Hospital
Nedlands, Western Australia, WA 6009
Linear Clinical Research
Nedlands, Western Australia, WA 6009
Calvary North Adelaide Hospital
North Adelaide, South Australia, SA 5006
Gold Coast University Hospital
Southport, Queensland, QLD 4215
Western Health Sunshine Hospital
St Albans, Victoria, VIC 3021
South Korea8 sites
Ulsan University Hospital
Donggu, Ulsan Gwang'Yeogsi, 44033
Gachon University Gil Medical Center
NamdongGu, Incheon Gwang'Yeogsi, 21565
The Catholic University of Korea, St Vincents Hospital
PaldalGu SuwonSi, Gyeonggi-do, 16247
The Catholic University of Korea, Seoul St Marys Hospital
SeochoGu, Seoul Teugbyeolsi, 06591
Severance Hospital Yonsei University Health System
SeodaemunGu, Seoul Teugbyeolsi, 03722
Chungbuk National University Hospital
SeowonGu CheongjuSi, Chungcheongbukdo, 28644
Asan Medical Center
SongpaGu, Seoul Teugbyeolsi, 05505
Ajou University Hospital
Suwon, 16499
Spain4 sites
Institut Catala Doncologia
Barcelona, 08908
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario Hm Madrid Sanchinarro
Madrid, 28050
Hospital Universitario Virgen Del Rocio
Seville, 41013
France3 sites
Centre de Lutte Contre Le Cancer Institut Bergonie
Bordeaux, 33000
Centre de Lutte Contre Le Cancer Francois Baclesse
Caen, 14000
Institut Curie Paris
Paris, 75005
Italy3 sites
Irccs Azienda Ospedaliero Universitaria Bologna
Bologna, 40138
Fondazione Irccs Istituto Nazionale Dei Tumori
Milan, 20133
Istituto Di Candiolo Irccs
Torino, 10060
About this study
Official 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
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.
Read the detailed description
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.
- 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
- Being tested
- Surzebiclimab, Tislelizumab, Alcestobart
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurzebiclimabDrug
Also called BGB-A425
Humanized immunoglobulin G1 (IgG1)-variant monoclonal antibody against TIM-3
TislelizumabDrug
Also called BGB-A317
Humanized, IgG4-variant monoclonal antibody against PD-1
AlcestobartDrug
Also called LBL-007
Human anti LAG-3 antibody
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab |
| 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. Receives: Drug: Surzebiclimab |
| 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. Receives: Drug: Tislelizumab; Drug: Alcestobart |
| 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. Receives: Drug: Tislelizumab; Drug: Alcestobart |
| 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. Receives: Drug: Tislelizumab; Drug: Alcestobart |
| 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. Receives: Drug: Tislelizumab; Drug: Alcestobart |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab; Drug: Alcestobart |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab; Drug: Alcestobart |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab; Drug: Alcestobart |
| 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. Receives: Drug: Surzebiclimab; Drug: Tislelizumab; Drug: Alcestobart |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Measured: Up to 30 days after last dose of study drug (maximum treatment duration: up to 32.7 months)
Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Surzebiclimab in Combination With Tislelizumab
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.
Measured: Up to 28 days
Phase 1: Recommended Phase 2 Dose (RP2D) of Surzebiclimab in Combination With Tislelizumab
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.
Measured: Up to 28 days
Phase 2 (Safety Lead-In): Number of Participants With TEAEs and SAEs
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.
Measured: 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)
Phase 2 (Safety Lead-In): MTD or MAD of Alcestobart in Combination With Tislelizumab
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.
Measured: Up to 21 days
Phase 2 (Safety Lead-In): MTD or MAD of Alcestobart in Combination With Surzebiclimab and Tislelizumab
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.
Measured: Up to 21 days
Phase 2 (Safety Lead-In): RP2D of Alcestobart in Combination With Surzebiclimab and Tislelizumab
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.
Measured: Up to 21 days
Phase 2 (Dose Expansion): Overall Response Rate (ORR)
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.
Measured: 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
Secondary outcomes (39)
Phase 1: Overall Response Rate (ORR)
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.
Measured: Maximum time on study: up to 57.5 months
Phase 2 (Safety Lead- In): Overall Response Rate (ORR)
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.
Measured: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months
Phase 1: Disease Control Rate (DCR)
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.
Measured: Maximum time on study: up to 57.5 months
Phase 2 (Safety Lead-In): Disease Control Rate (DCR)
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.
Measured: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months
Phase 2 (Dose Expansion): Disease Control Rate (DCR)
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.
Measured: 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
Phase 2 (Dose Expansion): Duration of Response (DOR)
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.
Measured: 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])
Phase 2 (Dose Expansion): Progression Free Survival (PFS)
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.
Measured: 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
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Surzebiclimab
The maximum observed plasma concentration of surzebiclimab was measured in Cycle 1 and Cycle 5.
Measured: 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.
Phase 2 (Dose Expansion): Cmax of Surzebiclimab
Measured: 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)
Phase 1: Minimum Observed Plasma Concentration (Cmin) of Surzebiclimab
Cmin of surzebiclimab was determined.
Measured: 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)
Phase 2 (Dose Expansion): Cmin of Surzebiclimab
Measured: 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
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Surzebiclimab
Measured: 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)
Phase 2 (Dose Expansion): Tmax of Surzebiclimab
Measured: 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)
Phase 1: Half-Life (t1/2) of Surzebiclimab
Measured: 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)
Phase 2 (Dose Expansion): T1/2 of Surzebiclimab
Measured: 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)
Phase 1: Area Under Curve From 0 to 21 Days (AUC0-21d) of Surzebiclimab
Measured: 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)
Phase 2 (Dose Expansion): AUC0-21d of Surzebiclimab
Measured: 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)
Phase 1: Clearance (CL/F) of Surzebiclimab
Measured: 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)
Phase 2 (Dose Expansion): CL/F of Surzebiclimab
Measured: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI
Phase 1: Volume of Distribution (Vz/F) of Surzebiclimab
Measured: 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)
Phase 2 (Dose Expansion): Vz/F of Surzebiclimab
Vz/F of surzebiclimab was determined.
Measured: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI
Phase 2 (Safety Lead-In): Cmax of Alcestobart
Measured: 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)
Phase 2 (Safety Lead-In): Cmin of Alcestobart
Cmin of alcestobart was determined.
Measured: 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)
Phase 2 (Safety Lead-In): Tmax of Alcestobart
Measured: 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)
Phase 2 (Safety Lead-In): t1/2 of Alcestobart
Measured: 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)
Phase 2 (Safety Lead-In): AUC0-21d of Alcestobart
Measured: 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)
Phase 2 (Safety Lead-In): CL/F of Alcestobart
Measured: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI
Phase 2 (Safety Lead-In): Vz/F of Alcestobart
Measured: Cycle 1 Day 1 at pre-dose, end of infusion (EOI), 6 hours, 1, 3, 7, 14, and 21 days after EOI
Phase 1: Serum Concentrations of Tislelizumab
Serum concentrations of tislelizumab were measured using an enzyme-linked immunosorbent assay (ELISA).
Measured: 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)
Phase 2 (Dose Expansion): Serum Concentrations of Tislelizumab
Serum concentrations of tislelizumab were measured using an enzyme-linked immunosorbent assay (ELISA).
Measured: 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)
Phase 1: Number of Participants With Anti-Drug Antibodies (ADA) to Surzebiclimab
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.
Measured: Maximum time on study: up to 57.5 months
Phase 2 (Safety Lead-In) Cohort B: Number of Participants With Anti-Drug Antibodies to Surzebiclimab
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.
Measured: Maximum time on study in Cohort B: up to 21.5 months
Phase 2 (Dose Expansion): Number of Participants With Anti-Drug Antibodies to Surzebiclimab
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.
Measured: 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
Phase 2 (Safety Lead-In): Number of Participants With Anti-Drug Antibodies to Alcestobart
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.
Measured: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months
Phase 2 (Dose Expansion) Cohorts 4 and 5: Number of Participants With Anti-Drug Antibodies to Alcestobart
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.
Measured: Maximum time on study: Cohort 4: up to 11.3 months, Cohort 5: up to 15.9 months
Phase 1: Number of Participants With Anti-Drug Antibodies to Tislelizumab
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.
Measured: Maximum time on study: up to 57.5 months
Phase 2 (Safety Lead-In): Number of Participants With Anti-Drug Antibodies to Tislelizumab
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.
Measured: Maximum time on study: Cohort A: up to 22.1 months; Cohort B: up to 21.5 months
Phase 2 (Dose Expansion): Number of Participants With Anti-Drug Antibodies to Tislelizumab
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.
Measured: 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
Phase 2 (Dose Expansion): Number of Participants With TEAEs and SAEs
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2018
- Study start13 Nov 2018
- Primary completion6 Feb 2025
- Study completion6 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Advanced or Metastatic Solid Tumors for Phase 1, Dose Escalation and Phase 2 Safety Lead-inStudies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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 alcestobart and tislelizumab with or without surzebiclimab. Phase 2 dose expansion continued to evaluate the safety but also focus on the efficacy of the double or triplet treatment combination in select tumor types.
- Masking
- None (open label)
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03744468
- Sponsor's protocol ID
- BGB-900-102
- Other IDs
- U1111-1278-0027, 2022-500694-14
- Status last verified
- Mar 2026
- First submitted
- 17 Oct 2018
- Last updated
- 2 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.