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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3475-555 | Other Identifier | MSD | |
| KEYNOTE-555 | Other Identifier | MSD | |
| 2019-001052-19 | EudraCT Number |
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The purpose of this study is to characterize the pharmacokinetic (PK) profile of pembrolizumab (MK-3475) following single subcutaneous (SC) injection of pembrolizumab Dose A versus pembrolizumab Dose C in adults with advanced melanoma. Additionally, the safety and tolerability of pembrolizumab SC injections will be assessed. And, finally, the efficacy of pembrolizumab intravenous (IV) infusion administration will be assessed.
This study consists of two cohorts. Participants in Cohort A are randomized to one of six treatment sequences which will include 2 cycles of pembrolizumab administered via subcutaneous injection and 1 cycle of intravenous (IV) infusion, followed by up to 32 cycles (up to ~2 years) of pembrolizumab administered via IV infusion (each cycle is 21 days). Participants in Cohort B will receive pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 18 cycles, up to ~ 2 years. Each cycle is 42 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A Pembrolizumab Treatment Sequence 1 | Experimental | Participants receive a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 165 mg/mL subcutaneously (SC); Cycle 2 Day 1: pembrolizumab 200 mg intravenously (IV); Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
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| Cohort A Pembrolizumab Treatment Sequence 2 | Experimental | Participants receive a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 165 mg/mL SC; Cycle 2 Day 1: pembrolizumab 130 mg/mL SC; Cycle 3 Day 1: pembrolizumab 200 mg IV; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
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| Cohort A Pembrolizumab Treatment Sequence 3 | Experimental | Participants receive a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 130 mg/mL SC; Cycle 2 Day 1: pembrolizumab 165 mg/mL SC; Cycle 3 Day 1: pembrolizumab 200 mg IV; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
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| Cohort A Pembrolizumab Treatment Sequence 4 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab Dose C | Biological | 165 mg/mL administered to a final dose of 285 mg via subcutaneous injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC) of Pembrolizumab - Cohort A | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at designated time points and a pharmacokinetic (PK) model based on historical intravenous pembrolizumab PK data were used for the determination of the AUC of pembrolizumab. Geometric least-square mean (GM) and 95% confidence intervals were derived from mixed-effects model performed on natural log-transformed values. Data were reported by treatment received. | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
| Maximum Plasma Concentration (Cmax) of Pembrolizumab - Cohort A | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points and a PK model based on historical intravenous pembrolizumab PK data were used for the determination of the AUC of pembrolizumab. GM and 95% confidence intervals were derived from mixed-effects model performed on natural log-transformed values. Data were reported by treatment received. | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
| Bioavailability (F) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the F of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Positive for Pembrolizumab Anti-Drug Antibody (ADA) Formation - Cohort A | Blood samples were collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The number of participants who develop anti-pembrolizumab antibodies were assessed in Cycles 1 through Cycle 4. Per ADA immunogenicity analysis report, data from participants in Cohort A were reported combined across treatment cycles 1-4. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orange Health Services ( Site 0004) | Orange | New South Wales | 2800 | Australia | ||
| Calvary Mater Newcastle ( Site 0006) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39531423 | Result | Cohen G, Rapoport B, Chan SW, Ruff P, Arance A, Mujika Eizmendi K, Houghton B, Brown MP, Zielinski RM, Munoz Couselo E, Lyle M, Anderson JR, Jain L, de Alwis D, Lala M, Akala O, Chartash E, Jacobs C. Pembrolizumab 400 mg every 6 weeks as first-line therapy for advanced melanoma (KEYNOTE-555): Results from cohort B of an open-label, phase 1 study. PLoS One. 2024 Nov 12;19(11):e0309778. doi: 10.1371/journal.pone.0309778. eCollection 2024. |
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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138 participants were randomized and 137 participants received at least one dose of study intervention.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A Pembrolizumab Treatment Sequence 1 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 165 mg/mL subcutaneously (SC); Cycle 2 Day 1: pembrolizumab 200 mg intravenously (IV); Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 19, 2021 |
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| Experimental |
Participants receive a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg SC; Cycle 2 Day 1: pembrolizumab 200 mg IV; Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab Dose 200 mg IV. |
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| Cohort A Pembrolizumab Treatment Sequence 5 | Experimental | Participants receive a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg IV; Cycle 2 Day 1: pembrolizumab 130 mg/mL SC; Cycle 3 Day 1: pembrolizumab 165 mg/mL SC: Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
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| Cohort A Pembrolizumab Treatment Sequence 6 | Experimental | Participants receive a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg IV; Cycle 2 Day 1: pembrolizumab 165 mg/mL SC; Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
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| Cohort B Pembrolizumab 400 mg IV | Experimental | Participants receive a single dose of pembrolizumab 400 mg IV on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for up to 18 cycles (up to approximately 2 years). |
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| Pembrolizumab Dose A | Biological | 130 mg/mL administered to a final dose of 285 mg via subcutaneous injection |
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| Pembrolizumab Dose B | Biological | 200 mg administered via intravenous infusion |
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| Pembrolizumab Dose D | Biological | 400 mg administered via intravenous infusion |
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| Absorption Rate Constant (Ka) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the Ka of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. Participants in Cohort B weren't analyzed, per protocol. | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
| Time of Maximum Plasma Concentration (Tmax) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points for the determination of the Tmax of pembrolizumab. | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
| Clearance (CL) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the CL of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
| Central Volume of Distribution (Vc) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the Vc of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Cohort B | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). Responses were based upon blinded independent central review (BICR) per RECIST 1.1. ORR was reported for participants in Cohort B. | Up to approximately 54 months |
| Cycles 1-4 Day 1: Predose. Each cycle is 21 days. (Up to approximately 64 days) |
| Number of Participants Who Experienced One or More Adverse Event (AEs) - Cohort A | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced one or more AEs in Cohort A was reported. Per protocol, data were reported by treatment received and AEs from Cycles 4-35 were reported separately. | Up to approximately 27 months |
| Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort A | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued due to an AE in Cohort A were reported. Per protocol, data were reported by treatment received and data from Cycles 4-35 were reported separately. | Up to approximately 23 months |
| Number of Participants With One or More Injection Site Signs and Symptoms After Subcutaneous Pembrolizumab Injection in Cycles 1-3 - Cohort A | Participants completed the Injection Site Signs and Symptoms Questionnaire, within 60 minutes after each pembrolizumab SC injection during Cycles 1-3. Participants rated any pain, itching, swelling and redness they experienced at the pembrolizumab SC injection site from "None" to "Severe". The number of participants who experienced an injection site sign or symptom was reported. | Cycles 1-3 Day 1: Up to 60 minutes postdose. Each cycle is 21 days. (Up to approximately 43 days) |
| Duration of Response (DOR) Per RECIST 1.1 - Cohort B | For participants who demonstrated a CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR was calculated for RECIST 1.1 based on BICR. DOR for Cohort B was reported. | Up to approximately 54 months |
| Progression-free Survival (PFS) Per to RECIST v1.1 Modified to Follow a Maximum of 10 Target Lesions and a Maximum of 5 Target Lesions Per Organ - Cohort B | PFS was defined as the time from the first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Although RECIST 1.1 was modified to allow for a maximum of 10 target lesions in total and 5 per organ. Per protocol, PFS as assessed by BICR for participants in Cohort B was reported. | Up to approximately 54 months |
| Overall Survival (OS) - Cohort B | OS was defined as the time from the first dose of study treatment to death due to any cause. Per protocol, OS for participants in Cohort B was reported. | Up to approximately 54 months |
| Early Cycle AUC of Pembrolizumab - Cohort B | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at designated time points for the determination of the pembrolizumab AUC in participants in Cohort B during Cycle 1 (early cycle). Blood samples were also collected predose on Day 1 of Cycle 2 just prior to the next dose as the last sample (trough concentration) of Cycle 1. A cycle was 42 days. | Cycle 1: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 2: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
| Steady State AUC of Pembrolizumab - Cohort B | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at designated time points for the determination of the pembrolizumab AUC in participants in Cohort B during Cycle 4 (steady state). Blood samples were also collected predose on Day 1 of Cycle 5 just prior to the next dose as the last samples (trough concentration) of Cycle 4. Each cycle was 42 days. | Cycle 4: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 5: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
| Early Cycle Cmax of Pembrolizumab - Cohort B | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmax in participants in Cohort B during Cycle 1 (early cycle). Blood samples were also collected predose on Day 1 of Cycle 2 just prior to the next dose as the last sample (trough concentration) of Cycle 1. Each cycle was 42 days. | Cycle 1: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 2: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
| Steady State Cmax of Pembrolizumab - Cohort B | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmax in participants in Cohort B during Cycle 4 (steady state). Blood samples were also collected predose on Day 1 of Cycle 5 just prior to the next dose as the last sample (trough concentration) of Cycle 4. Each cycle was 42 days. | Cycle 4: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 5: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
| Early Cycle Minimum Plasma Concentration (Cmin) of Pembrolizumab - Cohort B | Cmin was defined as the minimum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmin in participants in Cohort B during Cycle 1 (early cycle). Blood samples were also collected predose on Day 1 of Cycle 2 just prior to the next dose as the last sample (trough concentration) of Cycle 1. Each cycle was 42 days. | Cycle 1: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 2: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
| Steady State Cmin of Pembrolizumab - Cohort B | Cmin was defined as the minimum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmin in participants in Cohort B during Cycle 4 (steady state). Blood samples were also collected predose on Day 1 of Cycle 5 just prior to the next dose as the last sample (trough concentration) of Cycle 4. Each cycle was 42 days. | Cycle 4: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 5: Predose. Each Cycle was 42 days. (Up to approximately 6 weeks) |
| Number of Participants Who Experienced One or More AEs - Cohort B | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced one or more AEs in Cohort B was reported. | Up to approximately 54 months |
| Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort B | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued due to an AE in Cohort B were reported. | Up to approximately 26 months |
| Waratah |
| New South Wales |
| 2298 |
| Australia |
| Cairns and Hinterland Hospital and Health Service ( Site 0001) | Cairns | Queensland | 4870 | Australia |
| Royal Adelaide Hospital ( Site 0002) | Adelaide | South Australia | 5000 | Australia |
| Ballarat Health Services ( Site 0003) | Ballarat | 3350 | Australia |
| MNCCI Port Macquarie Base Hospital ( Site 0005) | Port Macquarie | 2444 | Australia |
| MPOC ( Site 0027) | Groenkloof Pretoria | Gauteng | 0181 | South Africa |
| WITS Clinical Research CMJAH Clinical Trial Site ( Site 0030) | Johannesburg | Gauteng | 2193 | South Africa |
| The Medical Oncology Centre of Rosebank ( Site 0026) | Johannesburg | Gauteng | 2196 | South Africa |
| Cape Town Oncology Trials Pty Ltd ( Site 0028) | Kraaifontein | Western Cape | 7570 | South Africa |
| Sandton Oncology Medical Group PTY LTD ( Site 0029) | Johannesburg | 2196 | South Africa |
| Hospital Universitari Vall d Hebron ( Site 0062) | Barcelona | 08035 | Spain |
| Hospital Clinic i Provincial de Barcelona ( Site 0061) | Barcelona | 08036 | Spain |
| Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0063) | Donostia / San Sebastian | 20014 | Spain |
| Karolinska Universitetssjukhuset Solna ( Site 0040) | Solna | 171 64 | Sweden |
| FG001 | Cohort A Pembrolizumab Treatment Sequence 2 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 165 mg/mL SC; Cycle 2 Day 1: pembrolizumab 130 mg/mL SC; Cycle 3 Day 1: pembrolizumab 200 mg IV; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| FG002 | Cohort A Pembrolizumab Treatment Sequence 3 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 130 mg/mL SC; Cycle 2 Day 1: pembrolizumab 165 mg/mL SC; Cycle 3 Day 1: pembrolizumab 200 mg IV; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| FG003 | Cohort A Pembrolizumab Treatment Sequence 4 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg SC; Cycle 2 Day 1: pembrolizumab 200 mg IV; Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab Dose 200 mg IV. |
| FG004 | Cohort A Pembrolizumab Treatment Sequence 5 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg IV; Cycle 2 Day 1: pembrolizumab 130 mg/mL SC; Cycle 3 Day 1: pembrolizumab 165 mg/mL SC: Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| FG005 | Cohort A Pembrolizumab Treatment Sequence 6 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg IV; Cycle 2 Day 1: pembrolizumab 165 mg/mL SC; Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| FG006 | Cohort B Pembrolizumab 400 mg IV | Participants received a single dose of pembrolizumab 400 mg IV on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for up to 18 cycles (up to approximately 2 years). |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A Pembrolizumab Treatment Sequence 1 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 165 mg/mL subcutaneously (SC); Cycle 2 Day 1: pembrolizumab 200 mg intravenously (IV); Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| BG001 | Cohort A Pembrolizumab Treatment Sequence 2 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 165 mg/mL SC; Cycle 2 Day 1: pembrolizumab 130 mg/mL SC; Cycle 3 Day 1: pembrolizumab 200 mg IV; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| BG002 | Cohort A Pembrolizumab Treatment Sequence 3 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 130 mg/mL SC; Cycle 2 Day 1: pembrolizumab 165 mg/mL SC; Cycle 3 Day 1: pembrolizumab 200 mg IV; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| BG003 | Cohort A Pembrolizumab Treatment Sequence 4 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg SC; Cycle 2 Day 1: pembrolizumab 200 mg IV; Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab Dose 200 mg IV. |
| BG004 | Cohort A Pembrolizumab Treatment Sequence 5 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg IV; Cycle 2 Day 1: pembrolizumab 130 mg/mL SC; Cycle 3 Day 1: pembrolizumab 165 mg/mL SC: Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| BG005 | Cohort A Pembrolizumab Treatment Sequence 6 | Participants received a single dose of pembrolizumab in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembrolizumab 200 mg IV; Cycle 2 Day 1: pembrolizumab 165 mg/mL SC; Cycle 3 Day 1: pembrolizumab 130 mg/mL SC; Cycle 4 Day 1 and every cycle thereafter, up to a total of 35 cycles (up to approximately 2 years), Day 1: pembrolizumab 200 mg IV. |
| BG006 | Cohort B Pembrolizumab 400 mg IV | Participants received a single dose of pembrolizumab 400 mg IV on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for up to 18 cycles (up to approximately 2 years). |
| BG007 | Total | Total of all reporting groups |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Area Under the Concentration-Time Curve (AUC) of Pembrolizumab - Cohort A | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at designated time points and a pharmacokinetic (PK) model based on historical intravenous pembrolizumab PK data were used for the determination of the AUC of pembrolizumab. Geometric least-square mean (GM) and 95% confidence intervals were derived from mixed-effects model performed on natural log-transformed values. Data were reported by treatment received. | All participants in Cohort A who were complaint with the study procedures and had available data from IV treatment and at least one SC treatment cycle were analyzed per protocol by treatment. Per protocol, participants in Cohort B were analyzed separately. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | mg*day/L | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
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| Primary | Maximum Plasma Concentration (Cmax) of Pembrolizumab - Cohort A | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points and a PK model based on historical intravenous pembrolizumab PK data were used for the determination of the AUC of pembrolizumab. GM and 95% confidence intervals were derived from mixed-effects model performed on natural log-transformed values. Data were reported by treatment received. | All participants in Cohort A who were complaint with the study procedures and had available data from IV treatment and at least one SC treatment cycle were analyzed per protocol by treatment. Per protocol, participants in Cohort B were analyzed separately. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | mg/L | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
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| Primary | Bioavailability (F) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the F of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. | All participants in Cohort A who were compliant with the study procedure and had available data from IV treatment and at least one SC treatment cycle were analyzed. Per protocol, data were pre-specified to be combined for participants in Cohort A; therefore data by individual dose were not analyzed. Participants in Cohort B weren't analyzed, per protocol. | Posted | Mean | 95% Confidence Interval | Percent | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
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| Primary | Absorption Rate Constant (Ka) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the Ka of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. Participants in Cohort B weren't analyzed, per protocol. | All participants in Cohort A who were compliant with the study procedure and had available data from IV treatment and at least one SC treatment cycle were analyzed. Per protocol, data were pre-specified to be combined for participants in Cohort A; therefore data by individual dose were not analyzed. Participants in Cohort B weren't analyzed, per protocol. | Posted | Mean | Standard Error | 1/day | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
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| Primary | Time of Maximum Plasma Concentration (Tmax) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points for the determination of the Tmax of pembrolizumab. | All participants in Cohort A who were complaint with the study procedures and had available data from IV treatment and at least one SC treatment cycle were analyzed per protocol by treatment. Per protocol, participants in Cohort B were not analyzed. | Posted | Median | Full Range | Days | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
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| Primary | Clearance (CL) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the CL of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. | All participants who were complaint with the study procedures and had available data from IV treatment and at least one SC treatment cycle were analyzed. Per protocol, data were pre-specified to be combined for participants in Cohort A; therefore data by individual dose were not analyzed. Participants in Cohort B weren't analyzed, per protocol. | Posted | Mean | Standard Error | Liters/day | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
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| Primary | Central Volume of Distribution (Vc) of Pembrolizumab - Cohort A | Blood samples were collected at designated time points and a population PK model based on historical intravenous pembrolizumab PK data was used for the determination of the Vc of pembrolizumab. Per protocol, an integrated population PK analysis was performed and combined data for Cohort A was reported. | All participants in Cohort A who were complaint with the study procedures and had available data from IV treatment and at least one SC treatment cycle were analyzed. Per protocol, data were pre-specified to be combined for participants in Cohort A; therefore data by individual dose were not analyzed. Participants in Cohort B weren't analyzed, per protocol. | Posted | Mean | Standard Error | Liters | Cycles 1-3: Day 1 Predose and Days 2, 5, 10 and 15; Cycle 4: Day 1 Predose. Samples were also collected after IV infusion on Cycles 1-3: Day 1 ~0.5 hours after infusion and after SC injection on Days 3, 4, 6, and 7. Each cycle was 21 days. |
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| Primary | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Cohort B | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). Responses were based upon blinded independent central review (BICR) per RECIST 1.1. ORR was reported for participants in Cohort B. | All randomized participants in Cohort B who received at least one dose of study intervention were analyzed. Per protocol, participants in Cohort A were not analyzed. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to approximately 54 months |
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| Secondary | Number of Participants Positive for Pembrolizumab Anti-Drug Antibody (ADA) Formation - Cohort A | Blood samples were collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The number of participants who develop anti-pembrolizumab antibodies were assessed in Cycles 1 through Cycle 4. Per ADA immunogenicity analysis report, data from participants in Cohort A were reported combined across treatment cycles 1-4. | All randomized participants in Cohort A who had at least one, conclusive ADA sample available after treatment with pembrolizumab in Cycles 1 through Cycle 4 were analyzed. Participants in Cohort B weren't analyzed, per protocol. | Posted | Count of Participants | Participants | Cycles 1-4 Day 1: Predose. Each cycle is 21 days. (Up to approximately 64 days) |
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| Secondary | Number of Participants Who Experienced One or More Adverse Event (AEs) - Cohort A | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced one or more AEs in Cohort A was reported. Per protocol, data were reported by treatment received and AEs from Cycles 4-35 were reported separately. | All randomized participants in Cohort A who received at least one dose of study intervention were analyzed. Per protocol, AEs from Cycles 4-35 were reported separately and participants in Cohort B were analyzed separately. | Posted | Count of Participants | Participants | Up to approximately 27 months |
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| Secondary | Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort A | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued due to an AE in Cohort A were reported. Per protocol, data were reported by treatment received and data from Cycles 4-35 were reported separately. | All participants in Cohort A who received at least one dose of study intervention were analyzed. All randomized participants in Cohort A who received at least one dose of study intervention were analyzed. Per protocol, data from Cycles 4-35 were reported separately and participants in Cohort B were analyzed separately. | Posted | Count of Participants | Participants | Up to approximately 23 months |
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| Secondary | Number of Participants With One or More Injection Site Signs and Symptoms After Subcutaneous Pembrolizumab Injection in Cycles 1-3 - Cohort A | Participants completed the Injection Site Signs and Symptoms Questionnaire, within 60 minutes after each pembrolizumab SC injection during Cycles 1-3. Participants rated any pain, itching, swelling and redness they experienced at the pembrolizumab SC injection site from "None" to "Severe". The number of participants who experienced an injection site sign or symptom was reported. | Per protocol, participants in Cohort A who received a subcutaneous dose of pembrolizumab were analyzed by treatment received. Therefore, data were not analyzed in participants who received IV infusion. Participants in Cohort B were not analyzed, per protocol. | Posted | Count of Participants | Participants | Cycles 1-3 Day 1: Up to 60 minutes postdose. Each cycle is 21 days. (Up to approximately 43 days) |
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| Secondary | Duration of Response (DOR) Per RECIST 1.1 - Cohort B | For participants who demonstrated a CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR was calculated for RECIST 1.1 based on BICR. DOR for Cohort B was reported. | All randomized participants in Cohort B who received at least one dose of study intervention and demonstrated a confirmed CR or PR response were analyzed. Per protocol, participants in Cohort A were not analyzed. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 54 months |
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| Secondary | Progression-free Survival (PFS) Per to RECIST v1.1 Modified to Follow a Maximum of 10 Target Lesions and a Maximum of 5 Target Lesions Per Organ - Cohort B | PFS was defined as the time from the first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Although RECIST 1.1 was modified to allow for a maximum of 10 target lesions in total and 5 per organ. Per protocol, PFS as assessed by BICR for participants in Cohort B was reported. | All randomized participants in Cohort B who received at least one dose of study intervention were analyzed. Per protocol, participants in Cohort A were not analyzed. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 54 months |
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| Secondary | Overall Survival (OS) - Cohort B | OS was defined as the time from the first dose of study treatment to death due to any cause. Per protocol, OS for participants in Cohort B was reported. | All randomized participants in Cohort B who received at least one dose of study intervention were analyzed. Per protocol, participants in Cohort A were not analyzed. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 54 months |
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| Secondary | Early Cycle AUC of Pembrolizumab - Cohort B | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at designated time points for the determination of the pembrolizumab AUC in participants in Cohort B during Cycle 1 (early cycle). Blood samples were also collected predose on Day 1 of Cycle 2 just prior to the next dose as the last sample (trough concentration) of Cycle 1. A cycle was 42 days. | All randomized participants in Cohort B who were compliant with the study procedures and had available data at the specified time point were analyzed. Per protocol, participants in Cohort A were analyzed separately. | Posted | Median | 90% Confidence Interval | μg/ml | Cycle 1: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 2: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
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| Secondary | Steady State AUC of Pembrolizumab - Cohort B | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at designated time points for the determination of the pembrolizumab AUC in participants in Cohort B during Cycle 4 (steady state). Blood samples were also collected predose on Day 1 of Cycle 5 just prior to the next dose as the last samples (trough concentration) of Cycle 4. Each cycle was 42 days. | All randomized participants in Cohort B who were compliant with the study procedures and had available data at the specified time point were analyzed. Per protocol, participants in Cohort A were analyzed separately. | Posted | Median | 90% Confidence Interval | μg/ml | Cycle 4: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 5: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
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| Secondary | Early Cycle Cmax of Pembrolizumab - Cohort B | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmax in participants in Cohort B during Cycle 1 (early cycle). Blood samples were also collected predose on Day 1 of Cycle 2 just prior to the next dose as the last sample (trough concentration) of Cycle 1. Each cycle was 42 days. | All randomized participants in Cohort B who were compliant with the study procedures and had available data at the specified time point were analyzed. Per protocol, participants in Cohort A were analyzed separately. | Posted | Median | 90% Confidence Interval | μg/ml | Cycle 1: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 2: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
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| Secondary | Steady State Cmax of Pembrolizumab - Cohort B | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmax in participants in Cohort B during Cycle 4 (steady state). Blood samples were also collected predose on Day 1 of Cycle 5 just prior to the next dose as the last sample (trough concentration) of Cycle 4. Each cycle was 42 days. | All randomized participants in Cohort B who were compliant with the study procedures and had available data at the specified time point were analyzed. Per protocol, participants in Cohort A were analyzed separately. | Posted | Median | 90% Confidence Interval | μg/ml | Cycle 4: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 5: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
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| Secondary | Early Cycle Minimum Plasma Concentration (Cmin) of Pembrolizumab - Cohort B | Cmin was defined as the minimum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmin in participants in Cohort B during Cycle 1 (early cycle). Blood samples were also collected predose on Day 1 of Cycle 2 just prior to the next dose as the last sample (trough concentration) of Cycle 1. Each cycle was 42 days. | All randomized participants in Cohort B who were compliant with the study procedures and had available data at the specified time point were analyzed. Per protocol, participants in Cohort A were not analyzed. | Posted | Median | 90% Confidence Interval | μg/ml | Cycle 1: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 2: Predose. A Cycle was 42 days. (Up to approximately 6 weeks) |
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| Secondary | Steady State Cmin of Pembrolizumab - Cohort B | Cmin was defined as the minimum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected at designated time points for the determination of the pembrolizumab Cmin in participants in Cohort B during Cycle 4 (steady state). Blood samples were also collected predose on Day 1 of Cycle 5 just prior to the next dose as the last sample (trough concentration) of Cycle 4. Each cycle was 42 days. | All randomized participants in Cohort B who were compliant with the study procedures and had available data at the specified time point were analyzed. Per protocol, participants in Cohort A were not analyzed. | Posted | Median | 90% Confidence Interval | μg/ml | Cycle 4: Day 1 Predose and ~5 minutes post infusion and Day 22; Cycle 5: Predose. Each Cycle was 42 days. (Up to approximately 6 weeks) |
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| Secondary | Number of Participants Who Experienced One or More AEs - Cohort B | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced one or more AEs in Cohort B was reported. | All randomized participants in Cohort B who received at least one dose of study intervention were analyzed. Per protocol, participants in Cohort A were analyzed separately. | Posted | Count of Participants | Participants | Up to approximately 54 months |
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| Secondary | Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort B | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued due to an AE in Cohort B were reported. | All randomized participants in Cohort B who received at least one dose of study intervention. Per protocol, participants in Cohort A were analyzed separately. | Posted | Count of Participants | Participants | Up to approximately 26 months |
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Up to approximately 54 months
Serious and Other adverse events (AEs) includes all participants who received ≥1 dose of study drug. All-Cause Mortality includes all randomized participants. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study treatment are excluded as AEs. Per protocol, data are reported by treatment received & data for Cohort A Cycles 4-35 was reported separately.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A Pembrolizumab 130 mg/mL SC | Participants received pembrolizumab 130 mg/mL via subcutaneous injection on Day 1 of a 21-day cycle. | 1 | 34 | 1 | 33 | 15 | 33 |
| EG001 | Cohort A Pembrolizumab 165 mg/mL SC | Participants received pembrolizumab 165 mg/mL via subcutaneous injection on Day 1 of a 21-day cycle. | 3 | 35 | 2 | 34 | 15 | 34 |
| EG002 | Cohort A Pembrolizumab 200 mg IV (Cycle 1 - Cycle 3) | Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21-day cycle. | 1 | 35 | 2 | 34 | 8 | 34 |
| EG003 | Cohort A Pembrolizumab 200 mg IV (Cycle 4 - Cycle 35) | In Cycle 4 through Cycle 35, participants received pembrolizumab 200 mg via intravenous injection on Day 1 of each 21-day cycle. | 4 | 31 | 9 | 30 | 27 | 30 |
| EG004 | Cohort B Pembrolizumab 400 mg IV | Participants received a single dose of pembrolizumab 400 mg IV on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for up to 18 cycles (up to approximately 2 years). | 45 | 101 | 31 | 101 | 93 | 101 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
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| Angina unstable | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Myocarditis | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hepatitis acute | Hepatobiliary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Immune-mediated adverse reaction | Immune system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
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| Soft tissue necrosis | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
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| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
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| Transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
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| Tumour compression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
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| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
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| Spinal cord compression | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
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| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
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| Ureterolithiasis | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
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| Prostatitis | Reproductive system and breast disorders | MedDRA 26.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pleural disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
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| Hyperthyroidism | Endocrine disorders | MedDRA 26.1 | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 26.1 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 26.1 | Systematic Assessment |
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| Folliculitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Tooth abscess | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood phosphorus increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood thyroid stimulating hormone decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
|
The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@msd.com |
| Nov 21, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided
| Death |
|
| Death |
|
| Physician Decision |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| GMR |
| 0.69 |
| 2-Sided |
| 90 |
| 0.64 |
| 0.74 |
| Other |
GMR = GM of Pembrolizumab 165 mg/mL SC/GM of Pembrolizumab 200 mg IV |
| OG002 |
| Cohort A Pembrolizumab 200 mg IV |
Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21-day cycle. |
|
|
|
| Cohort A Pembrolizumab 200 mg IV |
Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21-day cycle. |
| OG003 | Combined Cohort A | On Day 1 of Cycle 1 through Cycle 4, participants received one dose of the following: pembrolizumab 130 mg/mL via subcutaneous injection, pembrolizumab 165 mg/mL via subcutaneous injection, or pembrolizumab 200 mg via intravenous injection, depending on randomized treatment sequence. Each cycle was 21 days. |
|
|
| OG002 |
| Cohort A Pembrolizumab 200 mg IV |
Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21-day cycle. |
| OG003 | Combined Cohort A | On Day 1 of Cycle 1 through Cycle 4, participants received one dose of the following: pembrolizumab 130 mg/mL via subcutaneous injection, pembrolizumab 165 mg/mL via subcutaneous injection, or pembrolizumab 200 mg via intravenous injection, depending on randomized treatment sequence. Each cycle was 21 days. |
|
|
|
|
Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21-day cycle. |
| OG003 | Combined Cohort A | On Day 1 of Cycle 1 through Cycle 4, participants received one dose of the following: pembrolizumab 130 mg/mL via subcutaneous injection, pembrolizumab 165 mg/mL via subcutaneous injection, or pembrolizumab 200 mg via intravenous injection, depending on randomized treatment sequence. Each cycle was 21 days. |
|
|
| Cohort A Pembrolizumab 200 mg IV |
Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21-day cycle. |
| OG003 | Combined Cohort A | On Day 1 of Cycle 1 through Cycle 4, participants received one dose of the following: pembrolizumab 130 mg/mL via subcutaneous injection, pembrolizumab 165 mg/mL via subcutaneous injection, or pembrolizumab 200 mg via intravenous injection, depending on randomized treatment sequence. Each cycle was 21 days. |
|
|
|
| OG003 | Combined Cohort A | On Day 1 of Cycle 1 through Cycle 4, participants received one dose of the following: pembrolizumab 130 mg/mL via subcutaneous injection, pembrolizumab 165 mg/mL via subcutaneous injection, or pembrolizumab 200 mg via intravenous injection, depending on randomized treatment sequence. Each cycle was 21 days. |
|
|
| OG003 | Cohort A Pembrolizumab 200 mg IV (Cycle 4 - Cycle 35) | In Cycle 4 through Cycle 35, participants received pembrolizumab 200 mg via intravenous injection on Day 1 of each 21-day cycle. |
|
|
Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21-day cycle.
| OG003 | Cohort A Pembrolizumab 200 mg IV (Cycle 4 - Cycle 35) | In Cycle 4 through Cycle 35, participants received pembrolizumab 200 mg via intravenous injection on Day 1 of each 21-day cycle. |
|
|
Participants received pembrolizumab 200 mg via intravenous injection on Day 1 of a 21 day cycle. |
|
|
|
|
|
|
|
|
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