Melanoma
Conditions
Keywords
Programmed Cell Death 1, PD1, PD-1, Programmed Cell Death-Ligand 1, PDL1, PD-L1
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALPembrolizumab Dose C
165 mg/mL administered to a final dose of 285 mg via subcutaneous injection
BIOLOGICALPembrolizumab Dose A
130 mg/mL administered to a final dose of 285 mg via subcutaneous injection
BIOLOGICALPembrolizumab Dose B
200 mg administered via intravenous infusion
BIOLOGICALPembrolizumab Dose D
400 mg administered via intravenous infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically or cytologically confirmed diagnosis of advanced melanoma. * Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system not amenable to local therapy. * Has been untreated for advanced or metastatic disease except as follows: * a. BRAF V600 mutant melanoma may have received standard of care targeted therapy (e.g. BRAF/ mitogen-activated protein kinase kinase enzyme \[MEK\] inhibitor, alone or in combination) and be eligible for this study. * b. Prior adjuvant (post-surgery) or neoadjuvant (pre-surgery) melanoma therapy is permitted if it was completed ≥4 weeks before randomization and all related AEs have either returned to baseline or stabilized (resolution of toxic effect\[s\] of the most recent prior therapy to Grade 1 or less \[except alopecia\]). * Female participants must agree to use contraception during the treatment period and for ≥120 days after the last dose of study treatment. * Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Has adequate organ function.
Exclusion criteria
* Has received prior systemic treatment for unresectable or metastatic melanoma (exceptions as noted above in the Inclusion Criteria). * Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX-40 and CD137) or any other antibody or drug specifically targeting checkpoint pathways other than anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) which is permitted in the adjuvant setting. * Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. * Has received a live vaccine within 30 days prior to the first dose of study treatment. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. * Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. * Has known active central nervous system metastases and/or carcinomatous meningitis. * Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. * Has ocular melanoma. * Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has an active infection requiring systemic therapy. * Has a known history of human immunodeficiency virus (HIV) infection. * Has a known history of Hepatitis B or known active Hepatitis C virus infection. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment. * Has had an allogenic tissue/solid organ transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC) of Pembrolizumab - Cohort A | 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. | 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. |
| Maximum Plasma Concentration (Cmax) of Pembrolizumab - Cohort A | 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. | 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. |
| Bioavailability (F) of Pembrolizumab - Cohort A | 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. | 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. |
| Absorption Rate Constant (Ka) of Pembrolizumab - Cohort A | 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. | 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. |
| Time of Maximum Plasma Concentration (Tmax) of Pembrolizumab - Cohort A | 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. | Blood samples were collected at designated time points for the determination of the Tmax of pembrolizumab. |
| Clearance (CL) of Pembrolizumab - Cohort A | 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. | 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. |
| Central Volume of Distribution (Vc) of Pembrolizumab - Cohort A | 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. | 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. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Cohort B | Up to approximately 54 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steady State AUC of Pembrolizumab - Cohort B | 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) | 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. |
| Early Cycle Cmax of Pembrolizumab - Cohort B | 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) | 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. |
| Steady State Cmax of Pembrolizumab - Cohort B | 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) | 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. |
| Number of Participants Positive for Pembrolizumab Anti-Drug Antibody (ADA) Formation - Cohort A | Cycles 1-4 Day 1: Predose. Each cycle is 21 days. (Up to approximately 64 days) | 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. |
| Steady State Cmin of Pembrolizumab - Cohort B | 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) | 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. |
| Number of Participants Who Experienced One or More AEs - Cohort B | Up to approximately 54 months | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort B | Up to approximately 26 months | 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. |
| Early Cycle Minimum Plasma Concentration (Cmin) of Pembrolizumab - Cohort B | 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) | 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. |
| Number of Participants Who Experienced One or More Adverse Event (AEs) - Cohort A | Up to approximately 27 months | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort A | Up to approximately 23 months | 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. |
| Number of Participants With One or More Injection Site Signs and Symptoms After Subcutaneous Pembrolizumab Injection in Cycles 1-3 - Cohort A | Cycles 1-3 Day 1: Up to 60 minutes postdose. Each cycle is 21 days. (Up to approximately 43 days) | 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. |
| Duration of Response (DOR) Per RECIST 1.1 - Cohort B | Up to approximately 54 months | 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. |
| 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 | Up to approximately 54 months | 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. |
| Overall Survival (OS) - Cohort B | Up to approximately 54 months | 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. |
| Early Cycle AUC of Pembrolizumab - Cohort B | 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) | 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. |
Countries
Australia, South Africa, Spain, Sweden
Participant flow
Pre-assignment details
138 participants were randomized and 137 participants received at least one dose of study intervention.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 5 |
| 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. | 7 |
| 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). | 101 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 1 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 45 |
| Period 1 | Screen Failure | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
| Period 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 3 | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 3 | Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Period 4 | Adverse Event | 2 | 2 | 2 | 2 | 1 | 0 | 0 |
| Period 4 | Death | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Period 4 | Physician Decision | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A Pembrolizumab Treatment Sequence 1 | Cohort A Pembrolizumab Treatment Sequence 2 | Cohort A Pembrolizumab Treatment Sequence 3 | Cohort A Pembrolizumab Treatment Sequence 4 | Cohort A Pembrolizumab Treatment Sequence 5 | Cohort A Pembrolizumab Treatment Sequence 6 | Cohort B Pembrolizumab 400 mg IV | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 14.9 | 54.0 Years STANDARD_DEVIATION 20.1 | 58.2 Years STANDARD_DEVIATION 12.4 | 49.8 Years STANDARD_DEVIATION 16.7 | 59.8 Years STANDARD_DEVIATION 18 | 63.0 Years STANDARD_DEVIATION 22.5 | 62.1 Years STANDARD_DEVIATION 13.9 | 60.9 Years STANDARD_DEVIATION 14.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 3 Participants | 5 Participants | 93 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 8 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 7 Participants | 87 Participants | 124 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 36 Participants | 45 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 65 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 34 | 3 / 35 | 1 / 35 | 4 / 31 | 45 / 101 |
| other Total, other adverse events | 15 / 33 | 15 / 34 | 8 / 34 | 27 / 30 | 93 / 101 |
| serious Total, serious adverse events | 1 / 33 | 2 / 34 | 2 / 34 | 9 / 30 | 31 / 101 |
Outcome results
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Cohort A | Absorption Rate Constant (Ka) of Pembrolizumab - Cohort A | 0.191 1/day | Standard Error 13.1 |
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Area Under the Concentration-Time Curve (AUC) of Pembrolizumab - Cohort A | 507 mg*day/L |
| Cohort A Pembrolizumab 165 mg/mL SC | Area Under the Concentration-Time Curve (AUC) of Pembrolizumab - Cohort A | 480 mg*day/L |
| Cohort A Pembrolizumab 200 mg IV | Area Under the Concentration-Time Curve (AUC) of Pembrolizumab - Cohort A | 695 mg*day/L |
90% CI: [0.68, 0.78]
90% CI: [0.64, 0.74]
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Combined Cohort A | Bioavailability (F) of Pembrolizumab - Cohort A | 66 Percent |
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Cohort A | Central Volume of Distribution (Vc) of Pembrolizumab - Cohort A | 3.39 Liters | Standard Error 5.68 |
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Cohort A | Clearance (CL) of Pembrolizumab - Cohort A | 0.25 Liters/day | Standard Error 6.28 |
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Maximum Plasma Concentration (Cmax) of Pembrolizumab - Cohort A | 28.6 mg/L |
| Cohort A Pembrolizumab 165 mg/mL SC | Maximum Plasma Concentration (Cmax) of Pembrolizumab - Cohort A | 26.8 mg/L |
| Cohort A Pembrolizumab 200 mg IV | Maximum Plasma Concentration (Cmax) of Pembrolizumab - Cohort A | 71.3 mg/L |
90% CI: [0.36, 0.44]
90% CI: [0.34, 0.41]
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.
Time frame: Up to approximately 54 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Cohort B | 53.5 Percentage of Participants |
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Time of Maximum Plasma Concentration (Tmax) of Pembrolizumab - Cohort A | 6.55 Days |
| Cohort A Pembrolizumab 165 mg/mL SC | Time of Maximum Plasma Concentration (Tmax) of Pembrolizumab - Cohort A | 8.35 Days |
| Cohort A Pembrolizumab 200 mg IV | Time of Maximum Plasma Concentration (Tmax) of Pembrolizumab - Cohort A | 0.02 Days |
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.
Time frame: Up to approximately 54 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Duration of Response (DOR) Per RECIST 1.1 - Cohort B | NA Months |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Early Cycle AUC of Pembrolizumab - Cohort B | NA μg/ml |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Early Cycle Cmax of Pembrolizumab - Cohort B | 127.0 μg/ml |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Early Cycle Minimum Plasma Concentration (Cmin) of Pembrolizumab - Cohort B | 15.1 μg/ml |
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.
Time frame: Cycles 1-4 Day 1: Predose. Each cycle is 21 days. (Up to approximately 64 days)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Cohort A | Number of Participants Positive for Pembrolizumab Anti-Drug Antibody (ADA) Formation - Cohort A | 0 Participants |
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.
Time frame: Up to approximately 23 months
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort A | 1 Participants |
| Cohort A Pembrolizumab 165 mg/mL SC | Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort A | 0 Participants |
| Cohort A Pembrolizumab 200 mg IV | Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort A | 1 Participants |
| Combined Cohort A | Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort A | 5 Participants |
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.
Time frame: Up to approximately 26 months
Population: All randomized participants in Cohort B who received at least one dose of study intervention. Per protocol, participants in Cohort A were analyzed separately.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Number of Participants Who Discontinued Study Treatment Due to an AE - Cohort B | 8 Participants |
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.
Time frame: Up to approximately 27 months
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Number of Participants Who Experienced One or More Adverse Event (AEs) - Cohort A | 18 Participants |
| Cohort A Pembrolizumab 165 mg/mL SC | Number of Participants Who Experienced One or More Adverse Event (AEs) - Cohort A | 18 Participants |
| Cohort A Pembrolizumab 200 mg IV | Number of Participants Who Experienced One or More Adverse Event (AEs) - Cohort A | 14 Participants |
| Combined Cohort A | Number of Participants Who Experienced One or More Adverse Event (AEs) - Cohort A | 29 Participants |
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.
Time frame: Up to approximately 54 months
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Number of Participants Who Experienced One or More AEs - Cohort B | 101 Participants |
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.
Time frame: Cycles 1-3 Day 1: Up to 60 minutes postdose. Each cycle is 21 days. (Up to approximately 43 days)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Number of Participants With One or More Injection Site Signs and Symptoms After Subcutaneous Pembrolizumab Injection in Cycles 1-3 - Cohort A | 3 Participants |
| Cohort A Pembrolizumab 165 mg/mL SC | Number of Participants With One or More Injection Site Signs and Symptoms After Subcutaneous Pembrolizumab Injection in Cycles 1-3 - Cohort A | 2 Participants |
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.
Time frame: Up to approximately 54 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Overall Survival (OS) - Cohort B | NA Months |
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.
Time frame: Up to approximately 54 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | 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 | 13.8 Months |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Steady State AUC of Pembrolizumab - Cohort B | NA μg/ml |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Steady State Cmax of Pembrolizumab - Cohort B | 150.0 μg/ml |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A Pembrolizumab 130 mg/mL SC | Steady State Cmin of Pembrolizumab - Cohort B | 24.0 μg/ml |