A Phase 1 interventional study of Pembrolizumab 2 mg/kg and Pembrolizumab 10 mg/kg in Solid Tumor, Non-small Cell Lung Cancer and Small Cell Lung Cancer, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2021-06-22.
Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 1, Interventional, and Treatment
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.
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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.
In Part A, participants receive intravenous (IV) Pembrolizumab 2 mg/kg on Day 1 of Cycle 1 (28 days), Cycle 2 and any additional cycles (14 days).
Biological: Pembrolizumab 2 mg/kg
In Part A, participants receive IV Pembrolizumab 10 mg/kg on Day 1 of Cycle 1 (28 days), Cycle 2 and any additional cycles (14 days).
Biological: Pembrolizumab 10 mg/kg
In Part B, participants receive 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.
Biological: Pembrolizumab 200 mg · Drug: Cisplatin 75 mg/m^2 · Drug: Pemetrexed 500 mg/m^2
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.
Biological: Pembrolizumab 200 mg · Drug: Pemetrexed 500 mg/m^2 · Drug: Carboplatin AUC 5 mg/mL/min
In Part C, participants receive 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.
Biological: Pembrolizumab 200 mg · Drug: Carboplatin AUC 6 mg/mL/min · Drug: Paclitaxel 200 mg/m^2
In Part C, participants receive 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.
Biological: Pembrolizumab 200 mg · Drug: Carboplatin AUC 6 mg/mL/min · Drug: Nab-paclitaxel 100 mg/m^2
In Part D, participants receive 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).
Biological: Pembrolizumab 200 mg · Biological: Ipilimumab 1 mg/kg
In Part E, participants receive 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.
Biological: Pembrolizumab 200 mg · Drug: Cisplatin 75 mg/m^2 · Drug: Etoposide 100 mg/m^2
In Part E, participants receive 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.
Biological: Pembrolizumab 200 mg · Drug: Carboplatin AUC 5 mg/mL/min · Drug: Etoposide 100 mg/m^2
In Part E, participants receive 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.
Biological: Pembrolizumab 200 mg · Drug: Cisplatin 75 mg/m^2 · Drug: G-CSF (pegfilgrastim) 3.6 mg
Drug page: Pembrolizumab
Administered as an intravenous (IV) infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)
Also known as: KEYTRUDA®
Drug page: Pembrolizumab
Administered as an IV infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)
Also known as: KEYTRUDA®
Administered as an IV infusion on Day 1 of each 21-day cycle
Also known as: KEYTRUDA®
Drug page: Cisplatin
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug page: Pemetrexed
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
Drug page: Paclitaxel
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug page: Albumin-Bound Paclitaxel
Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle
Also known as: ABRAXANE®
Drug page: Ipilimumab
Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)
Also known as: YERVOY®
Drug page: Etoposide
Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle
Also known as: TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®
Administered as a subcutaneous injection on Day 4 of Cycle 1
Also known as: Neulasta®
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)
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
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
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)
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
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)
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
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
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
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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)
| Milestone | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 3 | 7 | 6 | 6 | 8 | 6 | 6 | 6 | 6 | 3 |
| Completed | 0 | 0 | 4 | 3 | 4 | 2 | 4 | 3 | 3 | 0 |
| Not completed | 3 | 7 | 2 | 3 | 4 | 4 | 2 | 3 | 3 | 3 |
| Withdrew: Status not recorded | 0 | 0 | 2 | 3 | 4 | 3 | 0 | 3 | 3 | 3 |
| Withdrew: Progressive disease | 3 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Ongoing in study | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Follow-up ended by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
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
| Participants | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part D: Pembrolizumab+Ipilimumab | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 3 | 0 | 0 |
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.
| Participants | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part D: Pembrolizumab+Ipilimumab | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event (AE) | 3 | 7 | 6 | 6 | 8 | 6 | 5 | 6 | 6 | 3 |
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.
| Participants | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part D: Pembrolizumab+Ipilimumab | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 0 | 0 | 1 | 5 | 4 | 3 | 2 | 1 | 1 | 0 |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part D: Pembrolizumab+Ipilimumab | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 47.4 ± 19 | 250 ± 23 | 52.51 ± 24.44 | 47.46 ± 17.04 | 56.39 ± 18.88 | 53.79 ± 14.18 | 72.71 ± 10.12 | 74.33 ± 14.04 | 84.55 ± 7.38 | 88.65 ± 19.14 |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A | 82.7 ± 12 | 322 ± 36 |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg | Part D: Pembrolizumab+Ipilimumab |
|---|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D | 93.0 ± 44 | 367 ± 35 | 86.21 ± 3.59 |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A | 115 ± 15 | 286 ± 19 |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E | 115 ± 15 | 298 ± NA | 124.47 ± NA | 95.51 ± 17.38 | 122.00 ± NA | 66.62 ± NA | 150.00 ± NA | 131.78 ± 9.46 | — |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A | 133 ± NA | 266 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A | — | 357 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A | — | 335 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A | — | 348 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A | — | 329 ± NA |
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.
| days | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part D: Pembrolizumab+Ipilimumab | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | 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 | 0.223 (0.00208 to 0.233) | 0.00903 (0.000694 to 0.232) | 1.98 (0.94 to 4.94) | 2.52 (0.033 to 13.91) | 0.028 (0.025 to 1.08) | 0.027 (0.022 to 1.02) | 0.026 (0.024 to 0.029) | 0.026 (0.026 to 0.029) | 0.028 (0.023 to 0.041) | 0.031 (0.025 to 0.033) |
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.
| days | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 4: Part D | 0.026 (0.025 to 0.030) |
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.
| days | Part B: Pembrolizumab+Cisplatin/Pemetrexed | Part B: Pembrolizumab+Carboplatin/Pemetrexed | Part C: Pembrolizumab+Carboplatin/Paclitaxel | Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|
| Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E | 0.024 (0.022 to 0.025) | 0.026 (0.025 to 0.026) | 0.028 (0.028 to 0.028) | 0.027 (0.024 to 0.029) | 0.029 (0.029 to 0.029) | 0.026 (0.023 to 0.031) | — |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part D: Pembrolizumab+Ipilimumab | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E | 11.2 ± 51 | 47.9 ± 50 | 19.88 ± 46.61 | 15.79 ± 33.24 | 9.45 ± 31.31 | 10.96 ± 17.19 | 8.26 ± 16.20 | 14.57 ± 10.56 | 15.30 ± 19.82 | 17.88 ± 9.58 |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D | 20.10 ± 24.59 |
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).
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D | 30.30 ± 19.38 |
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).
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E | 37.2 ± 13 | 83.0 ± 265 | 32.71 ± 30.35 | 25.38 ± 22.12 | 24.80 ± 9.28 | 23.63 ± 4.79 | 32.20 ± 21.52 | 30.43 ± 25.67 | 34.31 ± 22.05 |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D | 28.08 ± 23.62 |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E | 46.5 ± 12 | 38.3 ± 1640 | 37.70 ± 7.95 | 23.84 ± 69.26 | 35.33 ± 16.60 | 33.91 ± 14.66 | 47.82 ± 14.28 | 38.63 ± 25.56 | 46.47 ± NA |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D | 40.10 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E | 54.9 ± 13 | 134 ± NA | 39.33 ± NA | 37.44 ± 8.87 | 42.70 ± NA | 32.44 ± 29.15 | 54.0 ± NA | 48.92 ± 15.61 | 43.10 ± NA |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D | 35.20 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A | 68.4 ± NA | 125 ± NA |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D | 36.30 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E | — | 159 ± NA | 39.30 ± NA | 45.00 ± 6.84 | 32.60 ± NA | 57.80 ± NA | 52.20 ± NA | — | — |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D | 30.90 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A | — | 147 ± NA |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D | 28.40 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | 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/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E | — | 199 ± NA | 47.50 ± NA | 56.27 ± NA | — | — | 52.50 ± NA | — | — |
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.
| µg/mL | Part D: Pembrolizumab+Ipilimumab |
|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D | 30.70 ± NA |
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.
| µg/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A | — | 125 ± NA |
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.
| µg/mL | Part B: Pembrolizumab+Cisplatin/Pemetrexed | Part B: Pembrolizumab+Carboplatin/Pemetrexed | Part C: Pembrolizumab+Carboplatin/Paclitaxel | Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E | 48.50 ± NA | 50.98 ± NA | — | — | — | — | — |
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.
| µg/mL | Part B: Pembrolizumab+Cisplatin/Pemetrexed | Part B: Pembrolizumab+Carboplatin/Pemetrexed | Part C: Pembrolizumab+Carboplatin/Paclitaxel | Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E | 42.40 ± NA | 51.72 ± NA | — | — | — | — | — |
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.
| µg/mL | Part B: Pembrolizumab+Cisplatin/Pemetrexed | Part B: Pembrolizumab+Carboplatin/Pemetrexed | Part C: Pembrolizumab+Carboplatin/Paclitaxel | Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel | Part E: Pembrolizumab+Cisplatin/Etoposide | Part E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|
| Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E | 53.90 ± NA | 68.20 ± NA | — | — | — | — | — |
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.
| µg•day/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1 | 507 ± 20 | 2219 ± 32 |
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.
| µg•day/mL | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1 | 812 ± 45 | 3410 ± 56 |
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.
| days | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1 | 18.4 ± 56 | 18.1 ± 68 |
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.
| mL/kg | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1 | 65.3 ± 21 | 76.5 ± 34 |
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.
| mL/day/kg | Part A: Pembrolizumab 2 mg/kg | Part A: Pembrolizumab 10 mg/kg |
|---|---|---|
| Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1 | 2.46 ± 45 | 2.93 ± 56 |
Collected over Up to approximately 51.3 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A: Pembrolizumab 2 mg/kg | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Part A: Pembrolizumab 10 mg/kg | 0/7 (0%) | 1/7 (14.3%) | 7/7 (100%) |
| Part B: Pembrolizumab+Cisplatin/Pemetrexed | 5/6 (83.3%) | 2/6 (33.3%) | 6/6 (100%) |
| Part B: Pembrolizumab+Carboplatin/Pemetrexed | 5/6 (83.3%) | 5/6 (83.3%) | 6/6 (100%) |
| Part C: Pembrolizumab+Carboplatin/Paclitaxel | 5/8 (62.5%) | 3/8 (37.5%) | 8/8 (100%) |
| Part C: Pembrolizumab+Carboplatin/Nabpaclitaxel | 3/6 (50%) | 3/6 (50%) | 6/6 (100%) |
| Part D: Pembrolizumab+Ipilimumab | 4/6 (66.7%) | 1/6 (16.7%) | 5/6 (83.3%) |
| Part E: Pembrolizumab+Cisplatin/Etoposide | 5/6 (83.3%) | 3/6 (50%) | 6/6 (100%) |
| Part E: Pembrolizumab+Carboplatin/Etoposide | 5/6 (83.3%) | 2/6 (33.3%) | 6/6 (100%) |
| Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | 2/3 (66.7%) | 0/3 (0%) | 3/3 (100%) |
| Event | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 0/3 | 0/7 | 0/6 | 0/6 | 1/8 | 2/6 | 1/6 | 0/6 | 0/6 | 0/3 |
| Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders | 0/3 | 0/7 | 1/6 | 1/6 | 0/8 | 0/6 | 0/6 | 2/6 | 0/6 | 0/3 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 0/3 | 0/7 | 0/6 | 2/6 | 0/8 | 0/6 | 0/6 | 0/6 | 0/6 | 0/3 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/3 | 0/7 | 0/6 | 0/6 | 1/8 | 1/6 | 0/6 | 1/6 | 0/6 | 0/3 |
| DiarrhoeaGastrointestinal disorders | 0/3 | 0/7 | 0/6 | 0/6 | 0/8 | 1/6 | 0/6 | 0/6 | 0/6 | 0/3 |
| PyrexiaGeneral disorders | 0/3 | 0/7 | 0/6 | 1/6 | 0/8 | 0/6 | 0/6 | 0/6 | 0/6 | 0/3 |
| HepatitisHepatobiliary disorders | 0/3 | 0/7 | 1/6 | 0/6 | 0/8 | 0/6 | 0/6 | 0/6 | 0/6 | 0/3 |
| CellulitisInfections and infestations | 0/3 | 0/7 | 0/6 | 1/6 | 0/8 | 0/6 | 0/6 | 0/6 | 0/6 | 0/3 |
| InfluenzaInfections and infestations | 0/3 | 0/7 | 0/6 | 1/6 | 0/8 | 0/6 | 0/6 | 0/6 | 0/6 | 0/3 |
| DehydrationMetabolism and nutrition disorders | 0/3 | 0/7 | 0/6 | 0/6 | 0/8 | 1/6 | 0/6 | 0/6 | 0/6 | 0/3 |
| Event | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF |
|---|---|---|---|---|---|---|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 0/3 | 2/7 | 4/6 | 4/6 | 3/8 | 6/6 | 1/6 | 2/6 | 6/6 | 2/3 |
| LeukopeniaBlood and lymphatic system disorders | 0/3 | 0/7 | 4/6 | 4/6 | 4/8 | 6/6 | 0/6 | 6/6 | 6/6 | 2/3 |
| NeutropeniaBlood and lymphatic system disorders | 0/3 | 1/7 | 5/6 | 2/6 | 5/8 | 6/6 | 0/6 | 5/6 | 6/6 | 2/3 |
| ConstipationGastrointestinal disorders | 1/3 | 0/7 | 4/6 | 3/6 | 4/8 | 3/6 | 1/6 | 6/6 | 3/6 | 3/3 |
| NauseaGastrointestinal disorders | 1/3 | 1/7 | 6/6 | 5/6 | 3/8 | 5/6 | 0/6 | 3/6 | 2/6 | 3/3 |
| Decreased appetiteMetabolism and nutrition disorders | 0/3 | 3/7 | 6/6 | 3/6 | 4/8 | 6/6 | 2/6 | 3/6 | 5/6 | 2/3 |
| AlopeciaSkin and subcutaneous tissue disorders | 0/3 | 0/7 | 1/6 | 0/6 | 5/8 | 5/6 | 0/6 | 3/6 | 2/6 | 2/3 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/3 | 1/7 | 2/6 | 2/6 | 2/8 | 4/6 | 0/6 | 1/6 | 2/6 | 2/3 |
| VomitingGastrointestinal disorders | 0/3 | 1/7 | 2/6 | 0/6 | 2/8 | 3/6 | 0/6 | 0/6 | 1/6 | 2/3 |
| MalaiseGeneral disorders | 1/3 | 1/7 | 4/6 | 3/6 | 4/8 | 3/6 | 3/6 | 0/6 | 2/6 | 1/3 |
All randomized participants.
| Age, Continuous(Years) | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 61.3 ± 6.4 | 64.3 ± 13.6 | 57.3 ± 15.4 | 70.0 ± 6.0 | 66.6 ± 8.2 | 65.2 ± 11.8 | 66.0 ± 6.9 | 64.0 ± 3.6 | 64.7 ± 11.8 | 60.7 ± 8.1 | 64.4 ± 9.9 |
| Sex: Female, Male(Participants) | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 1 | 4 | 1 | 1 | 0 | 0 | 0 | 3 | 2 | 2 | 14 |
| Male | 2 | 3 | 5 | 5 | 8 | 6 | 6 | 3 | 4 | 1 | 43 |
| Ethnicity (NIH/OMB)(Participants) | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 3 | 7 | 6 | 6 | 8 | 6 | 6 | 6 | 6 | 3 | 57 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 3 | 7 | 6 | 6 | 8 | 6 | 6 | 6 | 6 | 3 | 57 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants) | Part A: Pembrolizumab 2 mg/kg | 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 E: Pembrolizumab+Carboplatin/Etoposide | Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ECOG = 0 | 2 | 2 | 3 | 2 | 1 | 1 | 0 | 2 | 2 | 3 | 18 |
| ECOG = 1 | 1 | 5 | 3 | 4 | 7 | 5 | 6 | 4 | 4 | 0 | 39 |
No study locations are listed for this record.
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Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Data sharing details ↗ · engagezone.msd.com
Ran from Apr 2013 to primary completion in Feb 2020, 82 months.
Results were first posted in Mar 2021, 1 year after primary completion.
Of 382 industry-sponsored phase 1 interventional studies under Carcinoma, Non-Small-Cell Lung, half reached primary completion within 47 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 69. This study's 82 months is above that.
Counting every sponsor, half of 588 studies reached it within 51 months; a quarter within 31 and three quarters within 74.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Pembrolizumab
Carcinoma, Non-Small-Cell Lung →