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)

NCT ID: NCT01840579

Last Updated: 2021-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-26
• Study Completion Date: 2020-02-28

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Pembrolizumab 2 mg/kg

Intervention Type: BIOLOGICAL

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

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).

Group Type: EXPERIMENTAL

Pembrolizumab 10 mg/kg

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Cisplatin 75 mg/m^2

Intervention Type: DRUG

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

Pemetrexed 500 mg/m^2

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Pemetrexed 500 mg/m^2

Intervention Type: DRUG

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

Carboplatin AUC 5 mg/mL/min

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Carboplatin AUC 6 mg/mL/min

Intervention Type: DRUG

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

Paclitaxel 200 mg/m^2

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Carboplatin AUC 6 mg/mL/min

Intervention Type: DRUG

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

Nab-paclitaxel 100 mg/m^2

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Ipilimumab 1 mg/kg

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Cisplatin 75 mg/m^2

Intervention Type: DRUG

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

Etoposide 100 mg/m^2

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Carboplatin AUC 5 mg/mL/min

Intervention Type: DRUG

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

Etoposide 100 mg/m^2

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg

Intervention Type: BIOLOGICAL

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

Cisplatin 75 mg/m^2

Intervention Type: DRUG

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

G-CSF (pegfilgrastim) 3.6 mg

Intervention Type: DRUG

Administered as a subcutaneous injection on Day 4 of Cycle 1

Interventions

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)

Intervention Type: 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)

Intervention Type: BIOLOGICAL

Pembrolizumab 200 mg

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

Intervention Type: BIOLOGICAL

Cisplatin 75 mg/m^2

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

Intervention Type: DRUG

Pemetrexed 500 mg/m^2

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

Intervention Type: DRUG

Carboplatin AUC 5 mg/mL/min

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

Intervention Type: DRUG

Carboplatin AUC 6 mg/mL/min

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

Intervention Type: DRUG

Paclitaxel 200 mg/m^2

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

Intervention Type: DRUG

Nab-paclitaxel 100 mg/m^2

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

Intervention Type: DRUG

Ipilimumab 1 mg/kg

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

Intervention Type: BIOLOGICAL

Etoposide 100 mg/m^2

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

Intervention Type: DRUG

G-CSF (pegfilgrastim) 3.6 mg

Administered as a subcutaneous injection on Day 4 of Cycle 1

Intervention Type: DRUG

Other Intervention Names

KEYTRUDA®; KEYTRUDA®; KEYTRUDA®; ABRAXANE®; YERVOY®; TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®; Neulasta®

Eligibility 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 27000274 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40036983 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38300341 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34607222 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trials Information

Other Identifiers

132249

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-011

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-011

Identifier Type: OTHER

Identifier Source: secondary_id

3475-011

Identifier Type: -

Identifier Source: org_study_id