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)

NCT01840579 | Completed Phase 1 Results

• 4 other identifiers: 3475-011132249MK-3475-011KEYNOTE-011
• Study Type: interventional
• Target: 57
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Solid Tumor; Non-small Cell Lung Cancer; Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)

  The following toxicities graded per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) were considered DLTs if judged by the investigator to be related to either study drug: * Grade (G) 4 neutropenia lasting \>7 days * Grade 3 and Grade 4 febrile neutropenia * Grade 4 thrombocytopenia (\<25,000/mm\^3) * Grade 4 anemia * Grade 4 non-hematologic toxicity (not laboratory) * Grade 3 non-hematologic toxicity (not laboratory) lasting \>3 days despite optimal supportive care * Any Grade 3 non-hematologic laboratory value if medical intervention is required to treat the participant or the abnormality persists for \>7 days. * (Part D only) Missing the second dose of pembrolizumab (Cycle1 Day 22) due to drug-related adverse event

  Cycle 1 (first dose and up to 4 weeks in Part A, 3 weeks in Parts B, C, E, and 6 weeks in Part D)

• Number of Participants Who Experienced at Least One Adverse Event (AE)

  An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

  Up to approximately 51.3 months

• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

  An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

  Up to approximately 37.9 months

Secondary Outcomes (39)

• Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E

  At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days)

• Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A

  Cycle 2 Day 1 pre- and post-dose

• Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D

  Cycle 4 Day 1 pre- and post-dose (Part A) and Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose (Part D)

• Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: 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

  Cycle 8 Day 1 pre- and post-dose

Study Arms (10)

Pembrolizumab 2 mg/kg

EXPERIMENTAL

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

Pembrolizumab 10 mg/kg

EXPERIMENTAL

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

Pembrolizumab+Cisplatin/Pemetrexed

EXPERIMENTAL

In Part B, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m\^2 + IV Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks.

Biological: Pembrolizumab 200 mg; Drug: Cisplatin 75 mg/m^2; Drug: Pemetrexed 500 mg/m^2

Pembrolizumab+Carboplatin/Pemetrexed

EXPERIMENTAL

In Part B, participants receive IV Pembrolizumab 200 mg + IV Carboplatin Area Under The Curve (AUC) 5 mg/mL/minute + IV Pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks.

Biological: Pembrolizumab 200 mg; Drug: Pemetrexed 500 mg/m^2; Drug: Carboplatin AUC 5 mg/mL/min

Pembrolizumab+Carboplatin/Paclitaxel

EXPERIMENTAL

In Part C, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute + IV Paclitaxel 200 mg/m\^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.

Biological: Pembrolizumab 200 mg; Drug: Carboplatin AUC 6 mg/mL/min; Drug: Paclitaxel 200 mg/m^2

Pembrolizumab+Carboplatin/Nab-paclitaxel

EXPERIMENTAL

In Part C, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute on Day 1 of each 21-day cycle + IV Nab-paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.

Biological: Pembrolizumab 200 mg; Drug: Carboplatin AUC 6 mg/mL/min; Drug: Nab-paclitaxel 100 mg/m^2

Pembrolizumab+Ipilimumab

EXPERIMENTAL

In Part D, participants receive IV Pembrolizumab 200 mg on Day 1 of each 21-day cycle + IV Ipilimumab 1 mg/kg on Day 1 of every other 21-day cycle (every 42 days) for a maximum of 18 cycles of Ipilimumab (35 doses of Pembrolizumab).

Biological: Pembrolizumab 200 mg; Biological: Ipilimumab 1 mg/kg

Pembrolizumab+Cisplatin/Etoposide

EXPERIMENTAL

In Part E, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m\^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.

Biological: Pembrolizumab 200 mg; Drug: Cisplatin 75 mg/m^2; Drug: Etoposide 100 mg/m^2

Pembrolizumab+Carboplatin/Etoposide

EXPERIMENTAL

In Part E, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 5 mg/mL/minute on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.

Biological: Pembrolizumab 200 mg; Drug: Carboplatin AUC 5 mg/mL/min; Drug: Etoposide 100 mg/m^2

Pembrolizumab+Cisplatin/Etoposide+G-CSF

EXPERIMENTAL

In Part E, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m\^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles + lasting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) 3.6 mg on Day 4 of Cycle 1. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.

Biological: Pembrolizumab 200 mg; Drug: Cisplatin 75 mg/m^2; Drug: G-CSF (pegfilgrastim) 3.6 mg

Interventions

Pembrolizumab 2 mg/kg BIOLOGICAL

Administered as an intravenous (IV) infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)

Also known as: KEYTRUDA®

Pembrolizumab 2 mg/kg

Pembrolizumab 10 mg/kg BIOLOGICAL

Administered as an IV infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)

Also known as: KEYTRUDA®

Pembrolizumab 10 mg/kg

Pembrolizumab 200 mg BIOLOGICAL

Administered as an IV infusion on Day 1 of each 21-day cycle

Also known as: KEYTRUDA®

Pembrolizumab+Carboplatin/Etoposide; Pembrolizumab+Carboplatin/Nab-paclitaxel; Pembrolizumab+Carboplatin/Paclitaxel; Pembrolizumab+Carboplatin/Pemetrexed; Pembrolizumab+Cisplatin/Etoposide; Pembrolizumab+Cisplatin/Etoposide+G-CSF; Pembrolizumab+Cisplatin/Pemetrexed; Pembrolizumab+Ipilimumab

Cisplatin 75 mg/m^2 DRUG

Administered as an IV infusion on Day 1 of each 21-day cycle

Pembrolizumab+Cisplatin/Etoposide; Pembrolizumab+Cisplatin/Etoposide+G-CSF; Pembrolizumab+Cisplatin/Pemetrexed

Pemetrexed 500 mg/m^2 DRUG

Administered as an IV infusion on Day 1 of each 21-day cycle

Pembrolizumab+Carboplatin/Pemetrexed; Pembrolizumab+Cisplatin/Pemetrexed

Carboplatin AUC 5 mg/mL/min DRUG

Administered as an IV infusion on Day 1 of each 21-day cycle

Pembrolizumab+Carboplatin/Etoposide; Pembrolizumab+Carboplatin/Pemetrexed

Carboplatin AUC 6 mg/mL/min DRUG

Administered as an IV infusion on Day 1 of each 21-day cycle

Pembrolizumab+Carboplatin/Nab-paclitaxel; Pembrolizumab+Carboplatin/Paclitaxel

Paclitaxel 200 mg/m^2 DRUG

Administered as an IV infusion on Day 1 of each 21-day cycle

Pembrolizumab+Carboplatin/Paclitaxel

Nab-paclitaxel 100 mg/m^2 DRUG

Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle

Also known as: ABRAXANE®

Pembrolizumab+Carboplatin/Nab-paclitaxel

Ipilimumab 1 mg/kg BIOLOGICAL

Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)

Also known as: YERVOY®

Pembrolizumab+Ipilimumab

Etoposide 100 mg/m^2 DRUG

Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle

Also known as: TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®

Pembrolizumab+Carboplatin/Etoposide; Pembrolizumab+Cisplatin/Etoposide

G-CSF (pegfilgrastim) 3.6 mg DRUG

Administered as a subcutaneous injection on Day 4 of Cycle 1

Also known as: Neulasta®

Pembrolizumab+Cisplatin/Etoposide+G-CSF

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (4)

• Shimizu T, Seto T, Hirai F, Takenoyama M, Nosaki K, Tsurutani J, Kaneda H, Iwasa T, Kawakami H, Noguchi K, Shimamoto T, Nakagawa K. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors. Invest New Drugs. 2016 Jun;34(3):347-54. doi: 10.1007/s10637-016-0347-6. Epub 2016 Mar 22.

  PMID: 27000274 RESULT

• Nogami N, Umemura S, Kozuki T, Zenke Y, Ohtani J, Ishii M, Han S, Noguchi K, Horinouchi H. A phase 1 study of pembrolizumab plus ipilimumab as first-line treatment in Japanese patients with advanced non-small-cell lung cancer. Respir Investig. 2025 May;63(3):296-302. doi: 10.1016/j.resinv.2025.02.010. Epub 2025 Mar 3.

  PMID: 40036983 DERIVED

• Nogami N, Tokito T, Zenke Y, Satouchi M, Seto T, Saka H, Ohtani J, Han S, Noguchi K, Nishio M. Phase 1 study of pembrolizumab plus chemotherapy in Japanese patients with extensive-stage small-cell lung cancer. Invest New Drugs. 2024 Feb;42(1):136-144. doi: 10.1007/s10637-023-01411-1. Epub 2024 Feb 1.

  PMID: 38300341 DERIVED

• Kurata T, Nakagawa K, Satouchi M, Seto T, Sawada T, Han S, Homma M, Noguchi K, Nogami N. Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. Cancer Treat Res Commun. 2021;29:100458. doi: 10.1016/j.ctarc.2021.100458. Epub 2021 Sep 15.

  PMID: 34607222 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Interventions

pembrolizumab; Cisplatin; Pemetrexed; Paclitaxel; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Ipilimumab; Etoposide; etoposide phosphate; Granulocyte Colony-Stimulating Factor; pegfilgrastim

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 25, 2013
• Study Start: April 26, 2013
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: June 22, 2021
• Results First Posted: March 22, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share