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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 : Active, not recruiting
First Posted : April 25, 2013
Last Update Posted : June 8, 2018
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

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 : May 29, 2018
Estimated Study Completion Date : April 17, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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 (14 days), and Cycle 3 (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 (14 days), and Cycle 3 (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 for up to 2 years.
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 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 for up to 2 years.
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 for up to 2 years.
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 for up to 2 years.
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 for up to 2 years.
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 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 for up to 2 years.
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 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 for up to 2 years.
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 experiencing dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (first dose up to 6 weeks) ]


Information from the National Library of Medicine

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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 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
Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications of Results:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01840579     History of Changes
Other Study ID Numbers: 3475-011
132249 ( Registry Identifier: JAPIC-CTI )
First Posted: April 25, 2013    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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
Pembrolizumab
Etoposide phosphate
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors