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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)

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ClinicalTrials.gov Identifier: NCT01840579
Recruitment Status : Completed
First Posted : April 25, 2013
Results First Posted : March 22, 2021
Last Update Posted : March 22, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study using pembrolizumab (MK-3475) will be done in 5 parts. In Part A, successive participant cohorts with advanced solid tumors will receive pembrolizumab to assess the safety and tolerability of monotherapy. In Parts B, C, and D, participants with advanced non-small cell lung cancer (NSCLC) will receive pembrolizumab in combination with either cisplatin/pemetrexed or carboplatin/pemetrexed (Part B); with either carboplatin/paclitaxel or carboplatin/nab-paclitaxel (Part C); or with ipilimumab (Part D) by non-random assignment to assess the safety and tolerability of the combination therapy. In Part E, participants with untreated Extensive-disease (ED) Small Cell Lung Cancer (SCLC) will receive pembrolizumab in combination with either cisplatin/etoposide, carboplatin/etoposide, or cisplatin/etoposide with prophylactic use of granulocyte colony-stimulating factor (lasting G-CSF [pegfilgrastim]) by non-random assignment to assess the safety and tolerability of the combination therapy.

Condition or disease Intervention/treatment Phase
Solid Tumor Non-small Cell Lung Cancer Small Cell Lung Cancer Biological: Pembrolizumab 2 mg/kg Biological: Pembrolizumab 10 mg/kg Biological: Pembrolizumab 200 mg Drug: Cisplatin 75 mg/m^2 Drug: Pemetrexed 500 mg/m^2 Drug: Carboplatin AUC 5 mg/mL/min Drug: Carboplatin AUC 6 mg/mL/min Drug: Paclitaxel 200 mg/m^2 Drug: Nab-paclitaxel 100 mg/m^2 Biological: Ipilimumab 1 mg/kg Drug: Etoposide 100 mg/m^2 Drug: G-CSF (pegfilgrastim) 3.6 mg Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : April 26, 2013
Actual Primary Completion Date : February 28, 2020
Actual Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: KEYTRUDA®

Biological: Ipilimumab 1 mg/kg
Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Neulasta®




Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E [ Time Frame: Cycle 1 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, D, and E on Day 1 of Cycle 1 at pre-dose and 0-30 minutes post-dose. 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 (%CV). Per protocol, analysis for Cmax in Cycle 1 was planned for Parts A, B, C, D, and E.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E [ Time Frame: Cycle 1 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 A, B, C, D, and E on Day 1 of Cycle 1 at pre-dose and 0-30 minutes post-dose. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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).

  17. 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).

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1 [ Time Frame: At designated timepoints in Part A Cycle 1 (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.

  36. Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1 [ Time Frame: At designated timepoints in Part A Cycle 1 (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.

  37. Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1 [ Time Frame: At designated timepoints in Part A Cycle 1 (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.

  38. Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1 [ Time Frame: At designated timepoints (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.

  39. Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1 [ Time Frame: At designated timepoints (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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01840579


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:
Additional Information:
Publications of Results:
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01840579    
Other Study ID Numbers: 3475-011
132249 ( Registry Identifier: JAPIC-CTI )
MK-3475-011 ( Other Identifier: Merck )
KEYNOTE-011 ( Other Identifier: Merck )
First Posted: April 25, 2013    Key Record Dates
Results First Posted: March 22, 2021
Last Update Posted: March 22, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Etoposide
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Pemetrexed
Ipilimumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors