Study of Pembrolizumab (MK-3475) Monotherapy in Advanced Solid Tumors and Pembrolizumab Combination Therapy in Advanced Non-small Cell Lung Cancer/ Extensive-disease Small Cell Lung Cancer (MK-3475-011/KEYNOTE-011)

May 28, 2021 updated by: Merck Sharp & Dohme LLC

A Phase I Study of MK-3475 Alone in Subjects With Advanced Solid Tumors and in Combination With Platinum-Doublet Chemotherapy or Immunotherapy in Subjects With Advanced Non-Small Cell Lung Cancer/Extensive-Disease Small Cell Lung Cancer.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab 2 mg/kg
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
Administered as an intravenous (IV) infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)
Other Names:
  • KEYTRUDA®
Experimental: Pembrolizumab 10 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
Administered as an IV infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)
Other Names:
  • KEYTRUDA®
Experimental: Pembrolizumab+Cisplatin/Pemetrexed
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
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Drug: Cisplatin 75 mg/m^2
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug: Pemetrexed 500 mg/m^2
Administered as an IV infusion on Day 1 of each 21-day cycle
Experimental: 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.
Biological: Pembrolizumab 200 mg
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Drug: Pemetrexed 500 mg/m^2
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug: Carboplatin AUC 5 mg/mL/min
Administered as an IV infusion on Day 1 of each 21-day cycle
Experimental: Pembrolizumab+Carboplatin/Paclitaxel
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
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Drug: Carboplatin AUC 6 mg/mL/min
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug: Paclitaxel 200 mg/m^2
Administered as an IV infusion on Day 1 of each 21-day cycle
Experimental: Pembrolizumab+Carboplatin/Nab-paclitaxel
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
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Drug: Carboplatin AUC 6 mg/mL/min
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug: Nab-paclitaxel 100 mg/m^2
Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle
Other Names:
  • ABRAXANE®
Experimental: Pembrolizumab+Ipilimumab
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
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Biological: Ipilimumab 1 mg/kg
Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)
Other Names:
  • YERVOY®
Experimental: Pembrolizumab+Cisplatin/Etoposide
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
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Drug: Cisplatin 75 mg/m^2
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug: Etoposide 100 mg/m^2
Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle
Other Names:
  • TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®
Experimental: Pembrolizumab+Carboplatin/Etoposide
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
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Drug: Carboplatin AUC 5 mg/mL/min
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug: Etoposide 100 mg/m^2
Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle
Other Names:
  • TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®
Experimental: Pembrolizumab+Cisplatin/Etoposide+G-CSF
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
Administered as an IV infusion on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
Drug: Cisplatin 75 mg/m^2
Administered as an IV infusion on Day 1 of each 21-day cycle
Drug: G-CSF (pegfilgrastim) 3.6 mg
Administered as a subcutaneous injection on Day 4 of Cycle 1
Other Names:
  • Neulasta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)
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)

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
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)
Time Frame: 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.
Up to approximately 51.3 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame: 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.
Up to approximately 37.9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: 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)
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.
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
Time Frame: 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.
Cycle 2 Day 1 pre- and post-dose
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: 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)
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.
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
Time Frame: 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.
Cycle 6 Day 1 pre- and post-dose
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E
Time Frame: 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.
Cycle 8 Day 1 pre- and post-dose
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A
Time Frame: 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.
Cycle 10 Day 1 pre- and post-dose
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A
Time Frame: 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.
Cycle 12 Day 1 pre- and post-dose
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A
Time Frame: 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.
Cycle 14 Day 1 pre- and post-dose
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A
Time Frame: 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.
Cycle 16 Day 1 pre- and post-dose
Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
Cycle 8 Day 1 pre- and post-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E
Time Frame: 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.
Cycle 2 Day 1 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D
Time Frame: 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.
Cycle 2 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D
Time Frame: 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).
Cycle 3 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E
Time Frame: 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).
Cycle 4 Day 1 at Pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D
Time Frame: 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.
Cycle 4 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E
Time Frame: 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.
Cycle 6 Day 1 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D
Time Frame: 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.
Cycle 6 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E
Time Frame: 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.
Cycle 8 Day 1 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D
Time Frame: 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.
Cycle 8 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A
Time Frame: 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.
Cycle 10 Day 1 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D
Time Frame: 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.
Cycle 10 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E
Time Frame: 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.
Cycle 12 Day 1 Pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D
Time Frame: 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.
Cycle 12 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A
Time Frame: 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.
Cycle 14 Day 1 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D
Time Frame: 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.
Cycle 14 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E
Time Frame: 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.
Cycle 16 Day 1 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D
Time Frame: 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.
Cycle 16 Day 22 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A
Time Frame: 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.
Cycle 18 Day 1 pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E
Time Frame: 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.
Cycle 20 Day 1 Pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E
Time Frame: 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.
Cycle 24 Day 1 Pre-dose
Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E
Time Frame: 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.
Cycle 28 Day 1 Pre-dose
Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2013

Primary Completion (Actual)

February 28, 2020

Study Completion (Actual)

February 28, 2020

Study Registration Dates

First Submitted

April 23, 2013

First Submitted That Met QC Criteria

April 23, 2013

First Posted (Estimate)

April 25, 2013

Study Record Updates

Last Update Posted (Actual)

June 22, 2021

Last Update Submitted That Met QC Criteria

May 28, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-011
  • 132249 (Registry Identifier: JAPIC-CTI)
  • MK-3475-011 (Other Identifier: Merck)
  • KEYNOTE-011 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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