Solid Tumor, Non-small Cell Lung Cancer, Small Cell Lung Cancer
Conditions
Brief summary
This study using pembrolizumab (MK-3475) will be done in 5 parts. In Part A, successive participant cohorts with advanced solid tumors will receive pembrolizumab to assess the safety and tolerability of monotherapy. In Parts B, C, and D, participants with advanced non-small cell lung cancer (NSCLC) will receive pembrolizumab in combination with either cisplatin/pemetrexed or carboplatin/pemetrexed (Part B); with either carboplatin/paclitaxel or carboplatin/nab-paclitaxel (Part C); or with ipilimumab (Part D) by non-random assignment to assess the safety and tolerability of the combination therapy. In Part E, participants with untreated Extensive-disease (ED) Small Cell Lung Cancer (SCLC) will receive pembrolizumab in combination with either cisplatin/etoposide, carboplatin/etoposide, or cisplatin/etoposide with prophylactic use of granulocyte colony-stimulating factor (lasting G-CSF \[pegfilgrastim\]) by non-random assignment to assess the safety and tolerability of the combination therapy.
Interventions
BIOLOGICALPembrolizumab 2 mg/kg
Administered as an intravenous (IV) infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)
BIOLOGICALPembrolizumab 10 mg/kg
Administered as an IV infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)
BIOLOGICALPembrolizumab 200 mg
Administered as an IV infusion on Day 1 of each 21-day cycle
Administered as an IV infusion on Day 1 of each 21-day cycle
Administered as an IV infusion on Day 1 of each 21-day cycle
DRUGCarboplatin AUC 5 mg/mL/min
Administered as an IV infusion on Day 1 of each 21-day cycle
DRUGCarboplatin AUC 6 mg/mL/min
Administered as an IV infusion on Day 1 of each 21-day cycle
Administered as an IV infusion on Day 1 of each 21-day cycle
Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle
BIOLOGICALIpilimumab 1 mg/kg
Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)
Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle
DRUGG-CSF (pegfilgrastim) 3.6 mg
Administered as a subcutaneous injection on Day 4 of Cycle 1
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* In Part A: has a histological or cytological diagnosis of solid tumor, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy * In Part B, C, and D: has a histologically- or cytologically-confirmed diagnosis of NSCLC (Stage IIIB/IV) and are naïve to systemic therapy * In Part C: has a histologically- or cytologically-confirmed diagnosis of squamous cancer * In Part E: has a histologically- or cytologically-confirmed diagnosis of SCLC (ED stage) and are naïve to systemic therapy * Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Has adequate organ function * Female participants of reproductive potential must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start) * Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 120 days after the last dose of study therapy and for up to 180 days after the last dose of chemotherapeutic agents
Exclusion criteria
* Has had cancer therapy within 2 weeks (Part E) or 4 weeks (Parts A, B, C, and D) prior to the first dose of study therapy, or not recovered from the adverse events of agents administered more than 4 weeks prior to the first dose of study therapy. * Part A: Chemotherapy, radiation therapy, biological therapy or kinase inhibitors * Parts B, C, D and E: Radiation therapy * For Part B: has a histological diagnosis of squamous cancer * Is currently participating or has participated in a study with an investigational agent or using an investigational device within 30 days of first dose of study therapy * Is expected to require any other form of antineoplastic therapy while on study * Is on chronic systemic steroid therapy within two weeks prior to the first dose of trial treatment or on any other form of immunosuppressive medication * For Part C: Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events version 4 criteria * Has interstitial lung disease detected by chest computed tomography (CT), or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | Cycle 1 (first dose and up to 4 weeks in Part A, 3 weeks in Parts B, C, E, and 6 weeks in Part D) | The following toxicities graded per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) were considered DLTs if judged by the investigator to be related to either study drug: * Grade (G) 4 neutropenia lasting \>7 days * Grade 3 and Grade 4 febrile neutropenia * Grade 4 thrombocytopenia (\<25,000/mm\^3) * Grade 4 anemia * Grade 4 non-hematologic toxicity (not laboratory) * Grade 3 non-hematologic toxicity (not laboratory) lasting \>3 days despite optimal supportive care * Any Grade 3 non-hematologic laboratory value if medical intervention is required to treat the participant or the abnormality persists for \>7 days. * (Part D only) Missing the second dose of pembrolizumab (Cycle1 Day 22) due to drug-related adverse event |
| Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to approximately 51.3 months | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | Up to approximately 37.9 months | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A | Cycle 6 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 6 at pre-dose and 0-30 minutes post-dose. Cycle 6 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 6 was only planned for Part A. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | Cycle 8 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Parts A, B, C and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 length for Part A was 14 days. Cycle 8 length for Parts B, C, and E was 21 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 8 was only planned for Parts A, B, C, and E. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A | Cycle 10 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 10 at pre-dose and 0-30 minutes post-dose. Cycle 10 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 10 was only planned for Part A. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A | Cycle 12 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 12 at pre-dose and 0-30 minutes post-dose. Cycle 12 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 12 was only planned for Part A. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A | Cycle 14 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 14 at pre-dose and 0-30 minutes post-dose. Cycle 14 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 14 was only planned for Part A. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A | Cycle 16 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 16 at pre-dose and 0-30 minutes post-dose. Cycle 16 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 16 was only planned for Part A. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A | Cycle 18 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose and 0-30 minutes post-dose. Cycle 18 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 18 was only planned for Part A. |
| Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days) | Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 1 was planned for Parts A, B, C, D, and E. |
| Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 4: Part D | Cycle 4 Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose | Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 4 was only planned for Part D. |
| Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | Cycle 8 Day 1 pre- and post-dose | Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 for Parts B, C, and E was 21 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 8was planned for Parts B, C, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | Cycle 2 Day 1 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 1 Ctrough was taken for Parts A, B, C, D, and E on Day 1 of Cycle 2 at pre-dose (prior to Cycle 2 infusion). Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 1 Ctrough was planned for Parts A, B, C, D, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D | Cycle 2 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 2 Ctrough was taken for Part D on Day 22 of Cycle 2 at pre-dose (prior to Cycle 3 infusion). Cycle 2 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 2 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D | Cycle 3 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Part D on Day 22 of Cycle 3 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | Cycle 4 Day 1 at Pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 4 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part A was 14 days. Cycle 3 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D | Cycle 4 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 4 Ctrough was taken for Part D on Day 22 of Cycle 4 at pre-dose (prior to Cycle 5 infusion). Cycle 4 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 4 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | Cycle 6 Day 1 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 5 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 6 at pre-dose (prior to Cycle 6 infusion). Cycle 5 length for Part A was 14 days. Cycle 5 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 5 Ctrough was only planned for Parts A, B, C, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D | Cycle 6 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 6 Ctrough was taken for Part D on Day 22 of Cycle 6 at pre-dose (prior to Cycle 7 infusion). Cycle 6 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 6 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | Cycle 8 Day 1 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 7 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 8 at pre-dose (prior to Cycle 8 infusion). Cycle 7 length for Part A was 14 days. Cycle 7 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 7 Ctrough was only planned for Parts A, B, C, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D | Cycle 8 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 8 Ctrough was taken for Part D on Day 22 of Cycle 8 at pre-dose (prior to Cycle 9 infusion). Cycle 8 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 8 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A | Cycle 10 Day 1 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 9 Ctrough was taken for Part A on Day 1 of Cycle 10 at pre-dose (prior to Cycle 10 infusion). Cycle 9 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 9 Ctrough was only planned for Part A. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D | Cycle 10 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 10 Ctrough was taken for Part D on Day 22 of Cycle 10 at pre-dose (prior to Cycle 11 infusion). Cycle 10 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 10 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | Cycle 12 Day 1 Pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 11 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 12 at pre-dose (prior to Cycle 12 infusion). Cycle 11 length for Part A was 14 days. Cycle 11 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 11 Ctrough was only planned for Parts A, B, C, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D | Cycle 12 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 12 Ctrough was taken for Part D on Day 22 of Cycle 12 at pre-dose (prior to Cycle 13 infusion). Cycle 12 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 12 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A | Cycle 14 Day 1 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 13 Ctrough was taken for Part A on Day 1 of Cycle 14 at pre-dose (prior to Cycle 14 infusion). Cycle 13 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 13 Ctrough was only planned for Part A. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D | Cycle 14 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 14 Ctrough was taken for Part D on Day 22 of Cycle 14 at pre-dose (prior to Cycle 15 infusion). Cycle 14 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 14 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E | Cycle 16 Day 1 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts A, B, C, and E on Day 1 of Cycle 16 at pre-dose (prior to Cycle 16 infusion). Cycle 15 length for Part A was 14 days. Cycle 15 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 15 Ctrough was only planned for Parts A, B, C, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D | Cycle 16 Day 22 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 16 Ctrough was taken for Part D on Day 22 of Cycle 16 at pre-dose (prior to Cycle 17 infusion). Cycle 16 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 16 Ctrough was only planned for Part D. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A | Cycle 18 Day 1 pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose (prior to Cycle 18 infusion). Cycle 17 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 17 Ctrough was planned for Part A. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E | Cycle 20 Day 1 Pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 20 at pre-dose (prior to Cycle 20 infusion). Cycle 19 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 19 Ctrough was only planned for Parts B, C, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E | Cycle 24 Day 1 Pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 24 at pre-dose (prior to Cycle 24 infusion). Cycle 23 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 23 Ctrough was only planned for Parts B, C, and E. |
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E | Cycle 28 Day 1 Pre-dose | Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 28 at pre-dose (prior to Cycle 28 infusion). Cycle 27 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 27 Ctrough was only planned for Parts B, C, and E. |
| Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1 | At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days) | AUC 0-28 was the AUC of pembrolizumab from time zero to 28 days after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-28 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-28 was only planned for Part A Cycle 1. |
| Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1 | At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days) | AUC 0-inf was the AUC of pembrolizumab from time zero to infinity after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-inf is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-inf was only planned for Part A Cycle 1. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days) | Cmax was the maximum observed concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Cmax was planned for Parts A, B, C, D, and E. |
| Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1 | At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days) | Vz was the volume of distribution during the terminal phase. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. Vz is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Vz was only planned for Part A Cycle 1. |
| Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1 | At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days) | CL was the volume of plasma from which pembrolizumab was eliminated per unit time. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. CL is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for CL was only planned for Part A Cycle 1. |
| Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1 | At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days) | t1/2 was the time required to divide the pembrolizumab concentration by two after reaching pseudo-equilibrium. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and pre-dose Day 1 of the following cycle prior to pembrolizumab infusion. Cycle 1 length A was 28 days. t1/2 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for t1/2 was only planned for Part A Cycle 1. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A | Cycle 2 Day 1 pre- and post-dose | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 2 at pre-dose and 0-30 minutes post-dose. Cycle 2 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 2 was only planned for Part A. |
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D | Cycle 4 Day 1 pre- and post-dose (Part A) and Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose (Part D) | Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 4 at pre-dose and 0-30 minutes post-dose and for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle 4 length for Part A was 14 days. Cycle 4 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 4 was only planned for Parts A and D. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: Pembrolizumab 2 mg/kg In Part A, participants received intravenous (IV) Pembrolizumab 2 mg/kg on Day 1 of Cycle 1 (28 days), Cycle 2 and any additional cycles (14 days). | 3 |
| Part A: Pembrolizumab 10 mg/kg In Part A, participants received IV Pembrolizumab 10 mg/kg on Day 1 of Cycle 1 (28 days), Cycle 2 and any additional cycles (14 days). | 7 |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed In Part B, participants received IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m\^2 + IV Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks. | 6 |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed In Part B, participants receive IV Pembrolizumab 200 mg + IV Carboplatin Area Under The Curve (AUC) 5 mg/mL/minute + IV Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks. | 6 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel In Part C, participants received IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute + IV Paclitaxel 200 mg/m\^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks. | 8 |
| Part C: Pembrolizumab+Carboplatin/Nabpaclitaxel In Part C, participants received IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute on Day 1 of each 21-day cycle + IV Nab-paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks. | 6 |
| Part D: Pembrolizumab+Ipilimumab In Part D, participants received IV Pembrolizumab 200 mg on Day 1 of each 21-day cycle + IV Ipilimumab 1 mg/kg on Day 1 of every other 21-day cycle (every 42 days) for a maximum of 18 cycles of Ipilimumab (35 doses of Pembrolizumab). | 6 |
| Part E: Pembrolizumab+Cisplatin/Etoposide In Part E, participants received IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m\^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks. | 6 |
| Part E: Pembrolizumab+Carboplatin/Etoposide In Part E, participants received IV Pembrolizumab 200 mg + IV Carboplatin AUC 5 mg/mL/minute on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks. | 6 |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF In Part E, participants received IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m\^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles + lasting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) 3.6 mg on Day 4 of Cycle 1. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks. | 3 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Follow-up ended by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Ongoing in study | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 3 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Status not recorded | 0 | 0 | 2 | 3 | 4 | 3 | 0 | 3 | 3 | 3 |
Baseline characteristics
| Characteristic | Part A: Pembrolizumab 10 mg/kg | Part B: Pembrolizumab+Cisplatin/Pemetrexed | Part B: Pembrolizumab+Carboplatin/Pemetrexed | Part C: Pembrolizumab+Carboplatin/Paclitaxel | Part C: Pembrolizumab+Carboplatin/Nabpaclitaxel | Part D: Pembrolizumab+Ipilimumab | Part E: Pembrolizumab+Cisplatin/Etoposide | Part A: Pembrolizumab 2 mg/kg | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.3 Years STANDARD_DEVIATION 13.6 | 57.3 Years STANDARD_DEVIATION 15.4 | 70.0 Years STANDARD_DEVIATION 6 | 66.6 Years STANDARD_DEVIATION 8.2 | 65.2 Years STANDARD_DEVIATION 11.8 | 66.0 Years STANDARD_DEVIATION 6.9 | 64.0 Years STANDARD_DEVIATION 3.6 | 61.3 Years STANDARD_DEVIATION 6.4 | 64.7 Years STANDARD_DEVIATION 11.8 | 60.7 Years STANDARD_DEVIATION 8.1 | 64.4 Years STANDARD_DEVIATION 9.9 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 0 | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 18 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 1 | 5 Participants | 3 Participants | 4 Participants | 7 Participants | 5 Participants | 6 Participants | 4 Participants | 1 Participants | 4 Participants | 0 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 3 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 3 Participants | 57 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 5 Participants | 8 Participants | 6 Participants | 6 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 43 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 7 | 5 / 6 | 5 / 6 | 5 / 8 | 3 / 6 | 4 / 6 | 5 / 6 | 5 / 6 | 2 / 3 |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 6 / 6 | 6 / 6 | 8 / 8 | 6 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 1 / 7 | 2 / 6 | 5 / 6 | 3 / 8 | 3 / 6 | 1 / 6 | 3 / 6 | 2 / 6 | 0 / 3 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Time frame: Up to approximately 37.9 months
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 0 Participants |
| Part A: Pembrolizumab 10 mg/kg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 0 Participants |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 1 Participants |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 5 Participants |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 4 Participants |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 3 Participants |
| Part D: Pembrolizumab+Ipilimumab | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 2 Participants |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 1 Participants |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 1 Participants |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 0 Participants |
Primary
Number of Participants Who Experienced at Least One Adverse Event (AE)
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Time frame: Up to approximately 51.3 months
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Number of Participants Who Experienced at Least One Adverse Event (AE) | 3 Participants |
| Part A: Pembrolizumab 10 mg/kg | Number of Participants Who Experienced at Least One Adverse Event (AE) | 7 Participants |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Number of Participants Who Experienced at Least One Adverse Event (AE) | 6 Participants |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Number of Participants Who Experienced at Least One Adverse Event (AE) | 6 Participants |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Number of Participants Who Experienced at Least One Adverse Event (AE) | 8 Participants |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Number of Participants Who Experienced at Least One Adverse Event (AE) | 6 Participants |
| Part D: Pembrolizumab+Ipilimumab | Number of Participants Who Experienced at Least One Adverse Event (AE) | 5 Participants |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Number of Participants Who Experienced at Least One Adverse Event (AE) | 6 Participants |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Number of Participants Who Experienced at Least One Adverse Event (AE) | 6 Participants |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Number of Participants Who Experienced at Least One Adverse Event (AE) | 3 Participants |
Primary
Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)
The following toxicities graded per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) were considered DLTs if judged by the investigator to be related to either study drug: * Grade (G) 4 neutropenia lasting \>7 days * Grade 3 and Grade 4 febrile neutropenia * Grade 4 thrombocytopenia (\<25,000/mm\^3) * Grade 4 anemia * Grade 4 non-hematologic toxicity (not laboratory) * Grade 3 non-hematologic toxicity (not laboratory) lasting \>3 days despite optimal supportive care * Any Grade 3 non-hematologic laboratory value if medical intervention is required to treat the participant or the abnormality persists for \>7 days. * (Part D only) Missing the second dose of pembrolizumab (Cycle1 Day 22) due to drug-related adverse event
Time frame: Cycle 1 (first dose and up to 4 weeks in Part A, 3 weeks in Parts B, C, E, and 6 weeks in Part D)
Population: The DLT analysis set included all participants who received at least at least 90% of the prescribed dose of pembrolizumab and the combination regimen and were evaluable for DLTs in the DLT evaluation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 Participants |
| Part A: Pembrolizumab 10 mg/kg | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 Participants |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 1 Participants |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 Participants |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 2 Participants |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 Participants |
| Part D: Pembrolizumab+Ipilimumab | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 Participants |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 3 Participants |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 Participants |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 Participants |
Secondary
Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1
AUC 0-28 was the AUC of pembrolizumab from time zero to 28 days after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-28 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-28 was only planned for Part A Cycle 1.
Time frame: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)
Population: The analysis population consisted of all participants who received pembrolizumab and had blood samples assessed for AUC 0-28 in Part A Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1 | 507 µg•day/mL | Geometric Coefficient of Variation 20 |
| Part A: Pembrolizumab 10 mg/kg | Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1 | 2219 µg•day/mL | Geometric Coefficient of Variation 32 |
Secondary
Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1
AUC 0-inf was the AUC of pembrolizumab from time zero to infinity after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-inf is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-inf was only planned for Part A Cycle 1.
Time frame: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)
Population: The analysis population consisted of all participants who received pembrolizumab and had blood samples assessed for AUC 0-inf in Part A Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1 | 812 µg•day/mL | Geometric Coefficient of Variation 45 |
| Part A: Pembrolizumab 10 mg/kg | Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1 | 3410 µg•day/mL | Geometric Coefficient of Variation 56 |
Secondary
Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1
CL was the volume of plasma from which pembrolizumab was eliminated per unit time. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. CL is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for CL was only planned for Part A Cycle 1.
Time frame: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)
Population: The analysis population consisted of all participants who received pembrolizumab and had blood samples assessed for CL in Part A Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1 | 2.46 mL/day/kg | Geometric Coefficient of Variation 45 |
| Part A: Pembrolizumab 10 mg/kg | Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1 | 2.93 mL/day/kg | Geometric Coefficient of Variation 56 |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 10 at pre-dose and 0-30 minutes post-dose. Cycle 10 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 10 was only planned for Part A.
Time frame: Cycle 10 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Part A Cycle 10.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A | 133 µg/mL |
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A | 266 µg/mL |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 12 at pre-dose and 0-30 minutes post-dose. Cycle 12 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 12 was only planned for Part A.
Time frame: Cycle 12 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Part A Cycle 12. There were no participants that contributed data for the analysis of Cmax for the 2 mg/kg arm in Part A of Cycle 12.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A | 357 µg/mL |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 14 at pre-dose and 0-30 minutes post-dose. Cycle 14 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 14 was only planned for Part A.
Time frame: Cycle 14 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Part A Cycle 14. There were no participants that contributed data for the analysis of Cmax for the 2 mg/kg arm in Part A of Cycle 14.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A | 335 µg/mL |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 16 at pre-dose and 0-30 minutes post-dose. Cycle 16 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 16 was only planned for Part A.
Time frame: Cycle 16 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Part A Cycle 16. There were no participants that contributed data for the analysis of Cmax for the 2 mg/kg arm in Part A of Cycle 16.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A | 348 µg/mL |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose and 0-30 minutes post-dose. Cycle 18 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 18 was only planned for Part A.
Time frame: Cycle 18 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Part A Cycle 18. There were no participants that contributed data for the analysis of Cmax for the 2 mg/kg arm in Part A of Cycle 18.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A | 329 µg/mL |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E
Cmax was the maximum observed concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Cmax was planned for Parts A, B, C, D, and E.
Time frame: At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days)
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Parts A, B, C, D, and E Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 47.4 µg/mL | Geometric Coefficient of Variation 19 |
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 250 µg/mL | Geometric Coefficient of Variation 23 |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 52.51 µg/mL | Geometric Coefficient of Variation 24.44 |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 47.46 µg/mL | Geometric Coefficient of Variation 17.04 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 56.39 µg/mL | Geometric Coefficient of Variation 18.88 |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 53.79 µg/mL | Geometric Coefficient of Variation 14.18 |
| Part D: Pembrolizumab+Ipilimumab | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 72.71 µg/mL | Geometric Coefficient of Variation 10.12 |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 74.33 µg/mL | Geometric Coefficient of Variation 14.04 |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 84.55 µg/mL | Geometric Coefficient of Variation 7.38 |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 88.65 µg/mL | Geometric Coefficient of Variation 19.14 |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 2 at pre-dose and 0-30 minutes post-dose. Cycle 2 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 2 was only planned for Part A.
Time frame: Cycle 2 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Part A Cycle 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A | 82.7 µg/mL | Geometric Coefficient of Variation 12 |
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A | 322 µg/mL | Geometric Coefficient of Variation 36 |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 4 at pre-dose and 0-30 minutes post-dose and for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle 4 length for Part A was 14 days. Cycle 4 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 4 was only planned for Parts A and D.
Time frame: Cycle 4 Day 1 pre- and post-dose (Part A) and Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose (Part D)
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Cycle 4 Parts A and D.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D | 93.0 µg/mL | Geometric Coefficient of Variation 44 |
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D | 367 µg/mL | Geometric Coefficient of Variation 35 |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D | 86.21 µg/mL | Geometric Coefficient of Variation 3.59 |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 6 at pre-dose and 0-30 minutes post-dose. Cycle 6 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 6 was only planned for Part A.
Time frame: Cycle 6 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Part A Cycle 6.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A | 115 µg/mL | Geometric Coefficient of Variation 15 |
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A | 286 µg/mL | Geometric Coefficient of Variation 19 |
Secondary
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E
Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Parts A, B, C and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 length for Part A was 14 days. Cycle 8 length for Parts B, C, and E was 21 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 8 was only planned for Parts A, B, C, and E.
Time frame: Cycle 8 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cmax in Parts A, B, C, and E Cycle 8. There were no participants that contributed data for the analysis of Cmax for the Pembrolizumab+Cisplatin/Etoposide+G-CSF arm in Part E of Cycle 8.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 115 µg/mL | Geometric Coefficient of Variation 15 |
| Part A: Pembrolizumab 10 mg/kg | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 298 µg/mL | — |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 124.47 µg/mL | — |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 95.51 µg/mL | Geometric Coefficient of Variation 17.38 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 122.00 µg/mL | — |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 66.62 µg/mL | — |
| Part D: Pembrolizumab+Ipilimumab | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 150.00 µg/mL | — |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 131.78 µg/mL | Geometric Coefficient of Variation 9.46 |
Secondary
Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1
t1/2 was the time required to divide the pembrolizumab concentration by two after reaching pseudo-equilibrium. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and pre-dose Day 1 of the following cycle prior to pembrolizumab infusion. Cycle 1 length A was 28 days. t1/2 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for t1/2 was only planned for Part A Cycle 1.
Time frame: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)
Population: The analysis population consisted of all participants who received pembrolizumab and had blood samples assessed for t1/2 in Part A Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1 | 18.4 days | Geometric Coefficient of Variation 56 |
| Part A: Pembrolizumab 10 mg/kg | Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1 | 18.1 days | Geometric Coefficient of Variation 68 |
Secondary
Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E
Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 1 was planned for Parts A, B, C, D, and E.
Time frame: At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days)
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Tmax in Parts A, B, C, D, and E Cycle 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.223 days |
| Part A: Pembrolizumab 10 mg/kg | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.00903 days |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 1.98 days |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 2.52 days |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.028 days |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.027 days |
| Part D: Pembrolizumab+Ipilimumab | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.026 days |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.026 days |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.028 days |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 0.031 days |
Secondary
Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 4: Part D
Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 4 was only planned for Part D.
Time frame: Cycle 4 Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for Tmax in the Cycle 4 analysis of Part D.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 4: Part D | 0.026 days |
Secondary
Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E
Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 for Parts B, C, and E was 21 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 8was planned for Parts B, C, and E.
Time frame: Cycle 8 Day 1 pre- and post-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Tmax in Parts B, C, and E Cycle 8. There were no participants that contributed data available for the analysis of Tmax for the Pembrolizumab+Cisplatin/Etoposide+G-CSF arm in Part E of Cycle 8.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | 0.024 days |
| Part A: Pembrolizumab 10 mg/kg | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | 0.026 days |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | 0.028 days |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | 0.027 days |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | 0.029 days |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | 0.026 days |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 10 Ctrough was taken for Part D on Day 22 of Cycle 10 at pre-dose (prior to Cycle 11 infusion). Cycle 10 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 10 Ctrough was only planned for Part D.
Time frame: Cycle 10 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 10 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D | 36.30 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 11 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 12 at pre-dose (prior to Cycle 12 infusion). Cycle 11 length for Part A was 14 days. Cycle 11 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 11 Ctrough was only planned for Parts A, B, C, and E.
Time frame: Cycle 12 Day 1 Pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 11 Ctrough in Parts A, B, C, and E. There were no participants that contributed data for the analysis of Ctrough for the Part A 2 mg/kg arm and Part E Pembrolizumab+Carboplatin/Etoposide and Pembrolizumab+Cisplatin/Etoposide+G-CSF arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | 159 µg/mL | — |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | 39.30 µg/mL | — |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | 45.00 µg/mL | Geometric Coefficient of Variation 6.84 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | 32.60 µg/mL | — |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | 57.80 µg/mL | — |
| Part D: Pembrolizumab+Ipilimumab | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | 52.20 µg/mL | — |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 12 Ctrough was taken for Part D on Day 22 of Cycle 12 at pre-dose (prior to Cycle 13 infusion). Cycle 12 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 12 Ctrough was only planned for Part D.
Time frame: Cycle 12 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 12 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D | 30.90 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 13 Ctrough was taken for Part A on Day 1 of Cycle 14 at pre-dose (prior to Cycle 14 infusion). Cycle 13 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 13 Ctrough was only planned for Part A.
Time frame: Cycle 14 Day 1 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 13 Ctrough in Part A. There were no participants that contributed data for the analysis of Ctrough for the Part A 2 mg/kg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A | 147 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 14 Ctrough was taken for Part D on Day 22 of Cycle 14 at pre-dose (prior to Cycle 15 infusion). Cycle 14 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 14 Ctrough was only planned for Part D.
Time frame: Cycle 14 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 14 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D | 28.40 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts A, B, C, and E on Day 1 of Cycle 16 at pre-dose (prior to Cycle 16 infusion). Cycle 15 length for Part A was 14 days. Cycle 15 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 15 Ctrough was only planned for Parts A, B, C, and E.
Time frame: Cycle 16 Day 1 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 15 Ctrough in Parts A, B, C, and E. There were no participants that contributed data for the analysis of Ctrough for the Part A 2 mg/kg arm; Part C Pembrolizumab+Carboplatin/Paclitaxel and Pembrolizumab+Carboplatin/Nab-paclitaxel arms; and Part E Pembrolizumab+Carboplatin/Etoposide and Pembrolizumab+Cisplatin/Etoposide+G-CSF arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E | 199 µg/mL |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E | 47.50 µg/mL |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E | 56.27 µg/mL |
| Part D: Pembrolizumab+Ipilimumab | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E | 52.50 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 16 Ctrough was taken for Part D on Day 22 of Cycle 16 at pre-dose (prior to Cycle 17 infusion). Cycle 16 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 16 Ctrough was only planned for Part D.
Time frame: Cycle 16 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 16 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D | 30.70 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose (prior to Cycle 18 infusion). Cycle 17 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 17 Ctrough was planned for Part A.
Time frame: Cycle 18 Day 1 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 17 Ctrough in Part A. There were no participants that contributed data for the analysis of Ctrough for the Part A 2 mg/kg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A | 125 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 20 at pre-dose (prior to Cycle 20 infusion). Cycle 19 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 19 Ctrough was only planned for Parts B, C, and E.
Time frame: Cycle 20 Day 1 Pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 19 Ctrough in Parts B, C, and E. There were no participants that contributed data for the analysis of Ctrough for the Part C Pembrolizumab+Carboplatin/Paclitaxel and Pembrolizumab+Carboplatin/Nab-paclitaxel arms; and Part E Pembrolizumab+Cisplatin/Etoposide, Pembrolizumab+Carboplatin/Etoposide, and Pembrolizumab+Cisplatin/Etoposide+G-CSF arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E | 48.50 µg/mL |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E | 50.98 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 1 Ctrough was taken for Parts A, B, C, D, and E on Day 1 of Cycle 2 at pre-dose (prior to Cycle 2 infusion). Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 1 Ctrough was planned for Parts A, B, C, D, and E.
Time frame: Cycle 2 Day 1 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 1 Ctrough in Parts A, B, C, D, and E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 11.2 µg/mL | Geometric Coefficient of Variation 51 |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 47.9 µg/mL | Geometric Coefficient of Variation 50 |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 19.88 µg/mL | Geometric Coefficient of Variation 46.61 |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 15.79 µg/mL | Geometric Coefficient of Variation 33.24 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 9.45 µg/mL | Geometric Coefficient of Variation 31.31 |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 10.96 µg/mL | Geometric Coefficient of Variation 17.19 |
| Part D: Pembrolizumab+Ipilimumab | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 8.26 µg/mL | Geometric Coefficient of Variation 16.2 |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 14.57 µg/mL | Geometric Coefficient of Variation 10.56 |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 15.30 µg/mL | Geometric Coefficient of Variation 19.82 |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 17.88 µg/mL | Geometric Coefficient of Variation 9.58 |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 24 at pre-dose (prior to Cycle 24 infusion). Cycle 23 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 23 Ctrough was only planned for Parts B, C, and E.
Time frame: Cycle 24 Day 1 Pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 23 Ctrough in Parts B, C, and E. There were no participants that contributed data for the analysis of Ctrough for the Part C Pembrolizumab+Carboplatin/Paclitaxel and Pembrolizumab+Carboplatin/Nab-paclitaxel arms; and Part E Pembrolizumab+Cisplatin/Etoposide, Pembrolizumab+Carboplatin/Etoposide, and Pembrolizumab+Cisplatin/Etoposide+G-CSF arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E | 42.40 µg/mL |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E | 51.72 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 28 at pre-dose (prior to Cycle 28 infusion). Cycle 27 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 27 Ctrough was only planned for Parts B, C, and E.
Time frame: Cycle 28 Day 1 Pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 27 Ctrough in Parts B, C, and E. There were no participants that contributed data for the analysis of Ctrough for the Part C Pembrolizumab+Carboplatin/Paclitaxel and Pembrolizumab+Carboplatin/Nab-paclitaxel arms; and Part E Pembrolizumab+Cisplatin/Etoposide, Pembrolizumab+Carboplatin/Etoposide, and Pembrolizumab+Cisplatin/Etoposide+G-CSF arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E | 53.90 µg/mL |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E | 68.20 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 2 Ctrough was taken for Part D on Day 22 of Cycle 2 at pre-dose (prior to Cycle 3 infusion). Cycle 2 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 2 Ctrough was only planned for Part D.
Time frame: Cycle 2 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 2 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D | 20.10 µg/mL | Geometric Coefficient of Variation 24.59 |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Part D on Day 22 of Cycle 3 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV).
Time frame: Cycle 3 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 3 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D | 30.30 µg/mL | Geometric Coefficient of Variation 19.38 |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 4 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part A was 14 days. Cycle 3 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV).
Time frame: Cycle 4 Day 1 at Pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 3 Ctrough in Parts A, B, C, and E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 37.2 µg/mL | Geometric Coefficient of Variation 13 |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 83.0 µg/mL | Geometric Coefficient of Variation 265 |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 32.71 µg/mL | Geometric Coefficient of Variation 30.35 |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 25.38 µg/mL | Geometric Coefficient of Variation 22.12 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 24.80 µg/mL | Geometric Coefficient of Variation 9.28 |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 23.63 µg/mL | Geometric Coefficient of Variation 4.79 |
| Part D: Pembrolizumab+Ipilimumab | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 32.20 µg/mL | Geometric Coefficient of Variation 21.52 |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 30.43 µg/mL | Geometric Coefficient of Variation 25.67 |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 34.31 µg/mL | Geometric Coefficient of Variation 22.05 |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 4 Ctrough was taken for Part D on Day 22 of Cycle 4 at pre-dose (prior to Cycle 5 infusion). Cycle 4 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 4 Ctrough was only planned for Part D.
Time frame: Cycle 4 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 4 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D | 28.08 µg/mL | Geometric Coefficient of Variation 23.62 |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 5 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 6 at pre-dose (prior to Cycle 6 infusion). Cycle 5 length for Part A was 14 days. Cycle 5 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 5 Ctrough was only planned for Parts A, B, C, and E.
Time frame: Cycle 6 Day 1 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 5 Ctrough in Parts A, B, C, and E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 46.5 µg/mL | Geometric Coefficient of Variation 12 |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 38.3 µg/mL | Geometric Coefficient of Variation 1640 |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 37.70 µg/mL | Geometric Coefficient of Variation 7.95 |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 23.84 µg/mL | Geometric Coefficient of Variation 69.26 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 35.33 µg/mL | Geometric Coefficient of Variation 16.6 |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 33.91 µg/mL | Geometric Coefficient of Variation 14.66 |
| Part D: Pembrolizumab+Ipilimumab | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 47.82 µg/mL | Geometric Coefficient of Variation 14.28 |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 38.63 µg/mL | Geometric Coefficient of Variation 25.56 |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 46.47 µg/mL | — |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 6 Ctrough was taken for Part D on Day 22 of Cycle 6 at pre-dose (prior to Cycle 7 infusion). Cycle 6 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 6 Ctrough was only planned for Part D.
Time frame: Cycle 6 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 6 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D | 40.10 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 7 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 8 at pre-dose (prior to Cycle 8 infusion). Cycle 7 length for Part A was 14 days. Cycle 7 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 7 Ctrough was only planned for Parts A, B, C, and E.
Time frame: Cycle 8 Day 1 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 7 Ctrough in Parts A, B, C, and E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 54.9 µg/mL | Geometric Coefficient of Variation 13 |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 134 µg/mL | — |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 39.33 µg/mL | — |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 37.44 µg/mL | Geometric Coefficient of Variation 8.87 |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 42.70 µg/mL | — |
| Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 32.44 µg/mL | Geometric Coefficient of Variation 29.15 |
| Part D: Pembrolizumab+Ipilimumab | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 54.0 µg/mL | — |
| Part E: Pembrolizumab+Cisplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 48.92 µg/mL | Geometric Coefficient of Variation 15.61 |
| Part E: Pembrolizumab+Carboplatin/Etoposide | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 43.10 µg/mL | — |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 8 Ctrough was taken for Part D on Day 22 of Cycle 8 at pre-dose (prior to Cycle 9 infusion). Cycle 8 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 8 Ctrough was only planned for Part D.
Time frame: Cycle 8 Day 22 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 8 Ctrough in Part D.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D | 35.20 µg/mL |
Secondary
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A
Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 9 Ctrough was taken for Part A on Day 1 of Cycle 10 at pre-dose (prior to Cycle 10 infusion). Cycle 9 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 9 Ctrough was only planned for Part A.
Time frame: Cycle 10 Day 1 pre-dose
Population: The analysis population consisted of all participants who received pembrolizumab and contributed blood samples for analysis of Cycle 9 Ctrough in Part A.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A | 68.4 µg/mL |
| Part A: Pembrolizumab 10 mg/kg | Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A | 125 µg/mL |
Secondary
Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1
Vz was the volume of distribution during the terminal phase. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. Vz is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Vz was only planned for Part A Cycle 1.
Time frame: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)
Population: The analysis population consisted of all participants who received pembrolizumab and had blood samples assessed for Vz in Part A Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1 | 65.3 mL/kg | Geometric Coefficient of Variation 21 |
| Part A: Pembrolizumab 10 mg/kg | Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1 | 76.5 mL/kg | Geometric Coefficient of Variation 34 |