Brief Summary
The primary objectives of this study were: to assess the safety and tolerability, to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and to determine the recommended Phase 2 dose (RP2D) of BGB-A1217 (known as ociperlimab) in combination with tislelizumab in participants with advanced solid tumors in phase 1.
Primary objective of Phase 1b was to assess overall response rate (ORR) determined by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1 for patients in each dose-expansion cohort.
Primary objective of Phase 1b was to assess overall response rate (ORR) determined by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1 for patients in each dose-expansion cohort.
Brief Title
Study of Ociperlimab (BGB-A1217) in Combination With Tislelizumab in Advanced Solid Tumors
Categories
Completion Date
Completion Date Type
Actual
Conditions
Locally Advanced and Metastatic Solid Tumors
Eligibility Criteria
Key Inclusion Criteria:
Phase 1 Key Inclusion Criteria
1. Had Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (\<=) 1.
2. Greater than or equal to (\>=) measurable lesion per RECIST v1.1.
3. Had adequate organ function.
4. Phase 1- Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who had previously received standard systemic therapy or for which treatment is not available, not tolerated or refused.
Phase 1b Key Inclusion Criteria
1. Signed informed consent form (ICF) and able to comply with study requirements.
2. Age \>= 18 years (or the legal age of consent) at the time the ICF was signed.
3. Histologically or cytologically confirmed tumor types in the following disease cohorts:
Cohort 1: stage IV squamous NSCLC Cohort 2: stage IV non-squamous NSCLC Cohort 3: stage IV squamous or non-squamous NSCLC with PD-L1 positive. Cohort 4: extensive-stage SCLC Cohort 5: stage IIIB, IIIC or IV NSCLC Cohort 6: stage IV ESCC Cohort 7: stage IV EAC Cohort 8: recurrent or metastatic HNSCC incurable by local therapies Cohort 9: stage IV G/GEJ adenocarcinoma. Cohort 10: stage IV squamous or non-squamous NSCLC with PD-L1 positive.
4. ECOG Performance Status \<= 1
5. Adequate organ function
6. Were willing to use highly effective method of birth control
Phase 1 Key Exclusion Criteria:
1. Active brain or leptomeningeal metastasis.
2. Active autoimmune diseases or history of autoimmune diseases that could have relapsed.
3. Had severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
4. Concurrent participation in another therapeutic clinical trial.
5. Received prior therapies targeting TIGIT.
Phase 1b Key Exclusion Criteria:
1. Participants with any prior therapy for recurrent/metastatic disease.
2. Non-squamous NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion.
3. Gastric cancer participants with squamous or with positive HER2 expression.
4. Prior therapy with any drug specifically targeting T-cell co-stimulation or checkpoint pathways. (anti-PD(L)1 exception for Cohort 5).
5. Active leptomeningeal disease or uncontrolled brain metastasis.
6. Active autoimmune diseases or history of autoimmune diseases that may relapse.
7. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for participants with hepatocellular carcinoma).
8. Concurrent participation in another therapeutic clinical study.
NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
Phase 1 Key Inclusion Criteria
1. Had Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (\<=) 1.
2. Greater than or equal to (\>=) measurable lesion per RECIST v1.1.
3. Had adequate organ function.
4. Phase 1- Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who had previously received standard systemic therapy or for which treatment is not available, not tolerated or refused.
Phase 1b Key Inclusion Criteria
1. Signed informed consent form (ICF) and able to comply with study requirements.
2. Age \>= 18 years (or the legal age of consent) at the time the ICF was signed.
3. Histologically or cytologically confirmed tumor types in the following disease cohorts:
Cohort 1: stage IV squamous NSCLC Cohort 2: stage IV non-squamous NSCLC Cohort 3: stage IV squamous or non-squamous NSCLC with PD-L1 positive. Cohort 4: extensive-stage SCLC Cohort 5: stage IIIB, IIIC or IV NSCLC Cohort 6: stage IV ESCC Cohort 7: stage IV EAC Cohort 8: recurrent or metastatic HNSCC incurable by local therapies Cohort 9: stage IV G/GEJ adenocarcinoma. Cohort 10: stage IV squamous or non-squamous NSCLC with PD-L1 positive.
4. ECOG Performance Status \<= 1
5. Adequate organ function
6. Were willing to use highly effective method of birth control
Phase 1 Key Exclusion Criteria:
1. Active brain or leptomeningeal metastasis.
2. Active autoimmune diseases or history of autoimmune diseases that could have relapsed.
3. Had severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
4. Concurrent participation in another therapeutic clinical trial.
5. Received prior therapies targeting TIGIT.
Phase 1b Key Exclusion Criteria:
1. Participants with any prior therapy for recurrent/metastatic disease.
2. Non-squamous NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion.
3. Gastric cancer participants with squamous or with positive HER2 expression.
4. Prior therapy with any drug specifically targeting T-cell co-stimulation or checkpoint pathways. (anti-PD(L)1 exception for Cohort 5).
5. Active leptomeningeal disease or uncontrolled brain metastasis.
6. Active autoimmune diseases or history of autoimmune diseases that may relapse.
7. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for participants with hepatocellular carcinoma).
8. Concurrent participation in another therapeutic clinical study.
NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
Phase 1 Key Inclusion Criteria
1. Had Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (\<=) 1.
2. Greater than or equal to (\>=) measurable lesion per RECIST v1.1.
3. Had adequate organ function.
4. Phase 1- Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who had previously received standard systemic therapy or for which treatment is not available, not tolerated or refused.
Phase 1b Key Inclusion Criteria
1. Signed informed consent form (ICF) and able to comply with study requirements.
2. Age \>= 18 years (or the legal age of consent) at the time the ICF was signed.
3. Histologically or cytologically confirmed tumor types in the following disease cohorts:
Cohort 1: stage IV squamous NSCLC Cohort 2: stage IV non-squamous NSCLC Cohort 3: stage IV squamous or non-squamous NSCLC with PD-L1 positive. Cohort 4: extensive-stage SCLC Cohort 5: stage IIIB, IIIC or IV NSCLC Cohort 6: stage IV ESCC Cohort 7: stage IV EAC Cohort 8: recurrent or metastatic HNSCC incurable by local therapies Cohort 9: stage IV G/GEJ adenocarcinoma. Cohort 10: stage IV squamous or non-squamous NSCLC with PD-L1 positive.
4. ECOG Performance Status \<= 1
5. Adequate organ function
6. Were willing to use highly effective method of birth control
Phase 1 Inclusion/
Phase 1 Key Inclusion Criteria
1. Had Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (\<=) 1.
2. Greater than or equal to (\>=) measurable lesion per RECIST v1.1.
3. Had adequate organ function.
4. Phase 1- Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who had previously received standard systemic therapy or for which treatment is not available, not tolerated or refused.
Phase 1b Key Inclusion Criteria
1. Signed informed consent form (ICF) and able to comply with study requirements.
2. Age \>= 18 years (or the legal age of consent) at the time the ICF was signed.
3. Histologically or cytologically confirmed tumor types in the following disease cohorts:
Cohort 1: stage IV squamous NSCLC Cohort 2: stage IV non-squamous NSCLC Cohort 3: stage IV squamous or non-squamous NSCLC with PD-L1 positive. Cohort 4: extensive-stage SCLC Cohort 5: stage IIIB, IIIC or IV NSCLC Cohort 6: stage IV ESCC Cohort 7: stage IV EAC Cohort 8: recurrent or metastatic HNSCC incurable by local therapies Cohort 9: stage IV G/GEJ adenocarcinoma. Cohort 10: stage IV squamous or non-squamous NSCLC with PD-L1 positive.
4. ECOG Performance Status \<= 1
5. Adequate organ function
6. Were willing to use highly effective method of birth control
Phase 1 Inclusion/
Gender
All
Gender Based
false
Keywords
BGB-A1217
Anti-TIGIT antibody
Tislelizumab
anti-PD-1 antibody
Ociperlimab
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04047862
Org Class
Industry
Org Full Name
BeiGene
Org Study Id
BGB-900-105
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase 1/1b Study Investigating Safety, Tolerability, PK and Antitumor Activity of Anti-TIGIT Monoclonal Antibody BGB-A1217 in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors
Primary Outcomes
Outcome Description
An AE was defined as any unfavorable and unintended sign, symptom, or disease associated with the use of study drugs, whether considered related to study drugs or not. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly or was considered a medically significant. Treatment-emergent adverse event (TEAE) was an AE that has an onset date or a worsening in severity from baseline on or after the first dose of study drug up to 30 days following study drug discontinuation or initiation of the first new systemic anticancer therapy, whichever occurred first. Severity of AEs was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v.5.0, which consists of: Grade 1 Mild; Grade 2 Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death due to AE.
Outcome Measure
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Outcome Time Frame
Up to 30 days after the last dose of study interventions (up to 35.7 months [Dose escalation cohorts] and up to 13.3 months [Dose verification cohorts])
Outcome Description
The DLTs were defined as high grade (Grade 3 or 4) non-hematologic toxicities (that is, \>= Grade 4 toxicity; Grade 3 toxicity that is clinically significant and does not resolve to baseline or \<=Grade 1 within 7 days of initiating optimal supportive care), or hematologic toxicities (Grade 4 neutropenia lasting \> 7 days; \>=Grade 3 febrile neutropenia; Grade 3 thrombocytopenia with clinically significant bleeding; Grade 4 thrombocytopenia lasting \> 7 days; \>=Grade 4 anemia occurring during the DLT assessment window and considered by the investigator to be related to ociperlimab and/or tislelizumab.
Outcome Measure
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Outcome Time Frame
Up to 28 days (for Dose escalation cohorts) and up to 21 days (for Dose verification cohorts)
Outcome Description
MAD was defined as the highest dose of ociperlimab administered.
Outcome Measure
Phase 1: Maximum Administered Dose (MAD) of Ociperlimab in Combination With Tislelizumab
Outcome Time Frame
Up to 28 days (Dose escalation cohort)
Outcome Description
RP2D of Ociperlimab in combination with Tislelizumab 200 mg was determined primarily from the safety, tolerability, and pharmacokinetic (PK) data of dose escalation cohorts.
Outcome Measure
Phase 1: Recommended Phase 2 Dose (RP2D) of Ociperlimab in Combination With Tislelizumab
Outcome Time Frame
up to 28 days (Dose escalation cohorts)
Outcome Description
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.
Outcome Measure
Phase 1b: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Outcome Time Frame
Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)
Secondary Ids
Secondary Id
AdvanTIG-105
Secondary Id
CTR20202608
Secondary Outcomes
Outcome Description
ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. Per RECIST v.1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Outcome Time Frame
Maximum time duration on study: up to 35.7 months (Dose escalation cohorts) and up to 13.3 months (Dose verification cohorts)
Outcome Measure
Phase 1: ORR as Per RECIST v.1.1
Outcome Description
DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of progression (PD) or death, whichever came first. DOR was estimated using the Kaplan-Meier method. Per RECIST v.1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Outcome Time Frame
From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: up to 35.7 months [Dose escalation cohorts] and up to 13.3 months [Dose verification cohorts])
Outcome Measure
Phase 1: Duration of Response (DOR) as Per RECIST v.1.1
Outcome Description
DCR was defined as the percentage of participants with best overall response (BOR), as per RECIST v.1.1, of a CR, PR, or stable disease (SD). Per RECIST v.1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Outcome Time Frame
From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: up to 35.7 months [Dose escalation cohorts] and up to 13.3 months [Dose verification cohorts])
Outcome Measure
Phase 1: Disease Control Rate (DCR) as Per RECIST v.1.1
Outcome Description
Serum concentrations of ociperlimab were measured. Post-dose refers to the data collected for 30 minutes post-infusion. "C" in the timeframe below refers to "Cycle" and D refers to "Day" and "h" refers to "hours".
Outcome Time Frame
C1D1 (pre and post dose; 24 hours (h) 72h, 168h and 336 h post-dose), C2D1 (pre- and post-dose), C5D1 (pre and post dose,168h and 336 h post-dose), C6D1 (pre and post-dose), pre-dose on C9D1,C13D1,C17D1,C25D1 (Cycle 1= 28 days; Cycle 2 onwards= 21 days)
Outcome Measure
Phase 1 (Dose Escalation): Serum Concentrations of Ociperlimab
Outcome Description
Serum Concentrations of Tislelizumab was determined. Post-dose refers to the data collected for 30 minutes post-infusion.
Outcome Time Frame
Cycle 1, Day 8 (pre-dose), Cycle 1, Day 8 (post-dose), Cycle 2, Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose), Cycle 5 Day 1 (post-dose), pre-dose of Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 25 Day 1 (each cycle = 21 days)
Outcome Measure
Phase 1 (Dose Escalation): Serum Concentrations of Tislelizumab
Outcome Description
Serum concentration of ociperlimab was determined. Post-dose refers to the data collected for 30 minutes post-infusion. "C" in the timeframe below refers to "Cycle" and D refers to "Day" and "h" refers to "hours".
Outcome Time Frame
Pre-dose, post-dose, 24 h,72 h,168 h,336 h post-dose C1D1, Pre-dose, post-dose on C2D1, Pre-dose, post-dose,168 h, 336 h post-dose on C5D1, Pre-dose, post-dose on C6D1, pre-dose C9D1 and C13D1 (each cycle = 21 days)
Outcome Measure
Phase 1 (Dose Verification): Serum Concentrations of Ociperlimab
Outcome Description
Serum concentrations of tislelizumab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.
Outcome Time Frame
Cycle 1 Day 1 (pre-dose), Cycle 1 Day 1 (post-dose), Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose), Cycle 5 Day 1 (post-dose), Cycle 6 Day 1 (pre-dose), Cycle 9 Day 1 (pre-dose), Cycle 13 Day 1 (pre-dose) (each cycle = 21 days)
Outcome Measure
Phase 1 (Dose Verification): Serum Concentrations of Tislelizumab
Outcome Description
Immunogenic responses to ociperlimab and tislelizumab included: treatment emergent, treatment-induced and treatment boosted anti-drug antibodies (ADA) and neutralizing antibody (NAb) positive assessments. Treatment-emergent ADA was defined as the sum of treatment-boosted ADA and treatment-induced ADA participants. Treatment-induced ADA was defined as ADA-evaluable participants that were ADA-negative at baseline and ADA-positive after drug administration during the treatment or follow-up observation period. Treatment-boosted ADA was defined as the Baseline-positive ADA-evaluable participants with significant increases (4-fold or higher) in ADA titer after drug administration during the treatment or follow-up observation period. NAb positive was defined as ADA-evaluable participants with positive Nab at any time including baseline and/or after drug administration.
Outcome Time Frame
Up to 32.2 months (Dose escalation cohorts) and up to 11 months (Dose verification cohorts)
Outcome Measure
Phase 1: Number of Participants With Immunogenic Response to Ociperlimab and Tislelizumab
Outcome Description
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.
Outcome Time Frame
From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: Up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10])
Outcome Measure
Phase 1b: DOR as Per RECIST v.1.1
Outcome Description
DCR was defined as the percentage of participants with BOR, as per RECIST v.1.1, of a CR, PR, or SD. Per Response evaluation criteria in solid tumors (RECIST) version (v)1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Outcome Time Frame
From the first determination of an overall response until PD or death, whichever came first (Maximum time duration on study: Up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10])
Outcome Measure
Phase 1b: DCR as Per RECIST v.1.1
Outcome Description
PFS was defined as the time from the date of the first dose of study drugs to the date of the first documentation of PD assessed by the investigator using RECIST v1.1 or death, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Outcome Time Frame
From first dose of study drugs to the date of the first documentation of PD or death, whichever came first (Maximum time duration on study: up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10])
Outcome Measure
Phase 1b: Progression Free Survival (PFS) as Per RECIST v.1.1
Outcome Description
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.
Outcome Time Frame
Up to 30 days after the last dose of study interventions (Maximum time duration on study: up to 41.6 months [Cohorts 1 to 9] and up to 21.4 months [Cohort 10])
Outcome Measure
Phase 1b (Cohorts 1-10): Number of Participants With TEAEs and TESAEs
Outcome Description
Serum concentrations of ociperlimab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.
Outcome Time Frame
Cycle 1 Day 1 (pre-dose), Cycle 1 Day 1 (post-dose), Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose and post-dose), pre-dose on Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1 and Cycle 25 Day 1 (each cycle = 21 days)
Outcome Measure
Phase 1b (Cohort 1-9): Serum Concentrations of Ociperlimab
Outcome Description
Serum concentrations of tislelizumab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.
Outcome Time Frame
Cycle 1 Day 1 (pre-dose and post-dose), Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose and post-dose), pre-dose on Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1 and Cycle 25 Day 1 (each cycle = 21 days)
Outcome Measure
Phase 1b (Cohort 1-9): Serum Concentrations of Tislelizumab
Outcome Description
Serum concentrations of ociperlimab were determined. Post-dose refers to the data collected for 30 minutes post-infusion and 'h' in the time-frame section refers to hours.
Outcome Time Frame
Pre-dose, post-dose, 168 h, 336 h post-dose Cycle1 Day 1, Pre-dose on Cycle 2 Day 1, Pre-dose, post-dose (30 min) on Cycle 5 Day 1, Pre-dose on Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, and Cycle 25 Day 1 (each cycle = 21 days)
Outcome Measure
Phase 1b (Cohort 10): Serum Concentrations of Ociperlimab
Outcome Description
Serum concentrations of tislelizumab were determined. Post-dose refers to the data collected for 30 minutes post-infusion.
Outcome Time Frame
Cycle 1 Day 1 (pre-dose and post-dose, Cycle 2 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose and post-dose), pre-dose of Cycle 6 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1 and Cycle 25 Day 1 (each cycle = 21 days)
Outcome Measure
Phase 1b (Cohort 10): Serum Concentrations of Tislelizumab
Outcome Description
Immunogenic responses to ociperlimab and tislelizumab included: treatment emergent, treatment-induced and treatment boosted ADA and NAb positive assessments. Treatment-emergent ADA was defined as the sum of treatment-boosted ADA and treatment-induced ADA participants. Treatment-induced ADA was defined as ADA-evaluable participants that were ADA-negative at baseline and ADA-positive after drug administration during the treatment or follow-up observation period. Treatment-boosted ADA was defined as the Baseline-positive ADA-evaluable participants with significant increases (4-fold or higher) in ADA titer after drug administration during the treatment or follow-up observation period. NAb positive was defined as ADA-evaluable participants with positive Nab at any time including baseline and/or after drug administration.
Outcome Time Frame
Up to 34.4 months (Cohorts 1 to 9) and up to 20.8 months (Cohort 10)
Outcome Measure
Phase 1b (Cohort 1-10): Number of Participants With Immunogenic Response to Ociperlimab and Tislelizumab
Outcome Description
Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression.
The TIGIT expression on immune cells (IC) and the classification thresholds were different for various cohorts. For Cohort 4, TIGIT IC was categorized as \<1% or \>=1%; for Cohorts 1, 2, 3, 5, 6, 8, 9 and 10, TIGIT IC was categorized as \<5% or \>=5%.
ORR is reported for each TIGIT subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
The TIGIT expression on immune cells (IC) and the classification thresholds were different for various cohorts. For Cohort 4, TIGIT IC was categorized as \<1% or \>=1%; for Cohorts 1, 2, 3, 5, 6, 8, 9 and 10, TIGIT IC was categorized as \<5% or \>=5%.
ORR is reported for each TIGIT subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
Outcome Time Frame
Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)
Outcome Measure
Phase 1b (Cohort 1-10): Percentage of Participants With ORR: TIGIT Biomarkers Expression
Outcome Description
Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression.
The PD-L1 expression scoring algorithm and the classification thresholds were also different for various cohorts as follows:
For Cohort 1 and Cohort 2, PD-L1 TC \<1% or \>= 1%; for Cohorts 3, 5, and 10, PD-L1 TC \< 50% or \>=50%; for Cohort 4, PD-L1 tumor area positivity (TAP) \<1% or \>=1%; for Cohort 9, PD-L1 TAP \< 5% or \>= 5%; for Cohort 6 and 8, PD-L1 TAP \<10% or \>=10%. ORR is reported for each PD-L1 subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
The PD-L1 expression scoring algorithm and the classification thresholds were also different for various cohorts as follows:
For Cohort 1 and Cohort 2, PD-L1 TC \<1% or \>= 1%; for Cohorts 3, 5, and 10, PD-L1 TC \< 50% or \>=50%; for Cohort 4, PD-L1 tumor area positivity (TAP) \<1% or \>=1%; for Cohort 9, PD-L1 TAP \< 5% or \>= 5%; for Cohort 6 and 8, PD-L1 TAP \<10% or \>=10%. ORR is reported for each PD-L1 subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
Outcome Time Frame
Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)
Outcome Measure
Phase 1b (Cohort 1-10): Percentage of Participants With ORR: PD-L1 Biomarkers Expression
Outcome Description
Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression.
The TIGIT expression on immune cells and the classification thresholds were different for various cohorts. For Cohort 4, TIGIT IC was categorized as \<1% or \>=1%; for Cohorts 1, 2, 3, 5, 6, 8, 9 and 10, TIGIT IC was categorized as \<5% or \>=5%. Median PFS (mPFS) is reported for each TIGIT subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
The TIGIT expression on immune cells and the classification thresholds were different for various cohorts. For Cohort 4, TIGIT IC was categorized as \<1% or \>=1%; for Cohorts 1, 2, 3, 5, 6, 8, 9 and 10, TIGIT IC was categorized as \<5% or \>=5%. Median PFS (mPFS) is reported for each TIGIT subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
Outcome Time Frame
Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)
Outcome Measure
Phase 1b (Cohort 1-10): PFS in TIGIT Biomarkers Expression
Outcome Description
Archival or fresh tumor samples were collected for analysis of biomarkers for T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and PD-L1 expression. The PD-L1 expression scoring algorithm and the classification thresholds were also different for various cohorts as follows:
For Cohort 1 and Cohort 2, PD-L1 TC \<1% or \>= 1%; for Cohorts 3, 5, and 10, PD-L1 TC \< 50% or \>=50%; for Cohort 4, PD-L1 tumor area positivity (TAP) \<1% or \>=1%; for Cohort 9, PD-L1 TAP \< 5% or \>= 5%; for Cohort 6 and 8, PD-L1 TAP \<10% or \>=10%. mPFS is reported for each PD-L1 subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
For Cohort 1 and Cohort 2, PD-L1 TC \<1% or \>= 1%; for Cohorts 3, 5, and 10, PD-L1 TC \< 50% or \>=50%; for Cohort 4, PD-L1 tumor area positivity (TAP) \<1% or \>=1%; for Cohort 9, PD-L1 TAP \< 5% or \>= 5%; for Cohort 6 and 8, PD-L1 TAP \<10% or \>=10%. mPFS is reported for each PD-L1 subgroup as relevant in each cohort. Biomarker data were not analyzed and reported for participants in Cohort 7.
Outcome Time Frame
Maximum time duration on study: up to 41.6 months (Cohorts 1 to 9) and up to 21.4 months (Cohort 10)
Outcome Measure
Phase 1b (Cohort 1-10): PFS in PD-L1 Biomarkers Expression
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- CAPECITABINE
MeSH Terms
TISLELIZUMAB
PEMETREXED
PACLITAXEL
ALBUMIN-BOUND PACLITAXEL
CARBOPLATIN
CISPLATIN
ETOPOSIDE
FLUOROURACIL
OXALIPLATIN
CAPECITABINE
GUANINE
HYPOXANTHINES
PURINONES
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
GLUTAMATES
AMINO ACIDS, ACIDIC
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
AMINO ACIDS, DICARBOXYLIC
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES
ALBUMINS
PROTEINS
COORDINATION COMPLEXES
CHLORINE COMPOUNDS
INORGANIC CHEMICALS
NITROGEN COMPOUNDS
PLATINUM COMPOUNDS
PODOPHYLLOTOXIN
TETRAHYDRONAPHTHALENES
NAPHTHALENES
POLYCYCLIC AROMATIC HYDROCARBONS
HYDROCARBONS, AROMATIC
POLYCYCLIC COMPOUNDS
GLUCOSIDES
GLYCOSIDES
CARBOHYDRATES
URACIL
PYRIMIDINONES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES