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| ID | Type | Description | Link |
|---|---|---|---|
| KEYNOTE-D85 | Other Identifier | Merck | |
| MK-3475-D85 | Other Identifier | Merck |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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The primary objective of Part A is to evaluate the safety and tolerability of S-531011 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of S-531011 with or without pembrolizumab.
The primary objective of Parts B and C is to evaluate the antitumor activity of S-531011 at the RP2D with or without pembrolizumab.
The primary objective of Parts D and E is to evaluate the antitumor activity of S-531011 at the RP2D in combination with bevacizumab with our without pembrolizumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A-1: S-531011 Monotherapy | Experimental | Participants will receive escalating doses of S-531011 by intravenous infusion for up to approximately 12 months. |
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| Part A-2: S-531011 + Pembrolizumab | Experimental | Participants will receive escalating doses of S-531011 in combination with pembrolizumab by intravenous infusion for up to approximately 24 months. |
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| Part B: S-531011 Monotherapy | Experimental | Participants will receive S-531011 at the RP2D by intravenous infusion for up to approximately 12 months. |
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| Part C: S-531011 + Pembrolizumab | Experimental | Participants will receive S-531011 at the RP2D in combination with pembrolizumab by intravenous infusion for up to approximately 24 months. |
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| Part D: S-531011 + Bevacizumab | Experimental | Participants will receive S-531011 at the RP2D in combination with bevacizumab or bevacizumab biosimilar by intravenous infusion for up to approximately 24 months. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| S-531011 | Drug | Administered by intravenous infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Approximately 12 months (Part A-1); Approximately 24 months (Part A-2) | |
| Parts B, C, D, E: Objective Response Rate | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E]) | |
| Parts B, C, D, E: Duration of Response | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E]) | |
| Parts B, C, D, E: Disease Control Rate | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E]) | |
| Parts B, C, D, E: Time to Response | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E]) | |
| Parts B, C, D, E: Progression-free Survival | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E]) | |
| Parts B, C, D, E: Overall Survival | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E]) |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Objective Response Rate | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2]) | |
| Part A: Duration of Response | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2]) |
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Eligibility Criteria: Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Additional protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shionogi Clinical Trials Administrator Clinical Support Help Line | Contact | 800-849-9707 | Shionogiclintrials-admin@shionogi.co.jp |
| Name | Affiliation | Role |
|---|---|---|
| Shionogi Clinical Trials Administrator Clinical Support Help Line | Shionogi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Angeles Clinic and Research Center | Active, not recruiting | Los Angeles | California | 90025 | United States | |
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| Part E: S-531011 + Bevacizumab + Pembrolizumab | Experimental | Participants will receive S-531011 at the RP2D in combination with bevacizumab or bevacizumab biosimilar and pembrolizumab by intravenous infusion for up to approximately 24 months. |
|
| Pembrolizumab | Drug | Administered by intravenous infusion |
|
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| Bevacizumab | Drug | Administered by intravenous infusion |
|
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| Part A: Disease Control Rate | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2]) |
| Part A: Time to Response | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2]) |
| Part A: Progression-free Survival | Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2]) |
| All Parts: Serum concentrations of S-531011 | Part A: Cycle 1, Days 8 and 15 (4 hours post infusion); Cycles 2-9, Day 1 (pre- and end-of-infusion); Safety Follow-up Visit. Parts B, C, D, E: Day 1 of Cycles 1-9 (pre- and end-of-infusion); Safety Follow-up Visit. (each cycle is 21 days) |
| Part A: Maximum Serum Concentration (Cmax) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Time to Maximum Serum Concentration (Tmax) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Area Under the Concentration-time Curve from Time Zero to the Time of Last Quantifiable Concentration After Dosing (AUC0-last) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Area Under the Concentration-time Curve Extrapolated from Time Zero to Infinity (AUC0-inf) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Terminal elimination rate constant (λz) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Terminal Elimination Half-life (t1/2,z) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Total Clearance (CL) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Volume of Distribution at Steady State (Vss) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| Part A: Mean Residence Time (MRT) of S-531011 | Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days) |
| All Parts: Anti-S-531011 Antibody (ADA) Titer Level | Day 1 of Cycles 1 to 9 (each cycle is 21 days) |
| All Parts: Anti-S-531011 Antibody (ADA) Titer Level | Neutralization assays will be performed only for the samples that are confirmed to have ADA. | Day 1 of Cycles 1 to 9 (each cycle is 21 days) |
| All Parts: Changes in serum tumor markers from pretreatment to on-treatment | Baseline and Day 1 of each treatment cycle (each cycle is 21 days) |
| Parts B, C, D, E: Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Approximately 12 months (Part B); Approximately 24 months (Parts C, D, E) |
| University of Florida Health |
| Recruiting |
| Gainesville |
| Florida |
| 32610 |
| United States |
| Henry Ford Health Center | Active, not recruiting | Detroit | Michigan | 48202 | United States |
| Fox Chase Cancer Center | Recruiting | Philadelphia | Pennsylvania | 19111 | United States |
| MD Anderson Cancer Center | Recruiting | Houston | Texas | 77030 | United States |
| National Cancer Center Hospital East | Recruiting | Kashiwa | Chiba | Japan |
| The University of Osaka Hospital | Recruiting | Suita | Osaka | Japan |
| National Cancer Center Hospital | Recruiting | Chuo Ku | Tokyo | Japan |
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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