Study of Pembrolizumab (MK-3475) Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (MK-3475-024/KEYNOTE-024)

NCT02142738 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 3475-024142728MK-3475-0242014-000323-25
• Study Type: interventional
• Target: 305
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies in the treatment of participants with previously untreated stage IV, programmed cell death ligand 1 (PD-L1) strong expressing Non-Small Cell Lung Cancer (NSCLC). The primary hypothesis of this study is that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when treated with pembrolizumab than when treated with SOC platinum-based chemotherapies. With Amendment 09 (20 December 2017), once participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.

Conditions

Non-Small Cell Lung Carcinoma

Keywords

Programmed cell death-1 (PD-1); Programmed cell death 1 (PD1); Programmed death-ligand 1 (PDL1); PD-L1

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Rate at Month 6

  PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent central radiologists' (BICR) review. Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. (Note: the appearance of one or more new lesions was also considered progression). Participants were evaluated every 9 weeks with radiographic imaging to assess their response to treatment. The data cutoff was 09-May-2016. The PFS rate at Month 6 was calculated.

  Month 6

Secondary Outcomes (2)

• Overall Survival (OS) Rate

  12 months

• Objective Response Rate (ORR)

  Up to ~1.6 years

Study Arms (6)

Pembrolizumab

EXPERIMENTAL

Participants receive pembrolizumab 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles.

Drug: Pembrolizumab

Paclitaxel+Carboplatin

ACTIVE COMPARATOR

Participants receive paclitaxel 200 mg/m\^2 and carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for participants with non-squamous histologies for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Pemetrexed

Pemetrexed+Carboplatin

ACTIVE COMPARATOR

Participants receive pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6, IV infusion on Day 1 of each 21-day cycle for 4-6 cycles; participants with non-squamous histologies may then receive pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle as maintenance therapy for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Drug: Carboplatin; Drug: Pemetrexed

Pemetrexed+Cisplatin

ACTIVE COMPARATOR

Participants receive pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m\^2 Q3W maintenance for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Drug: Pemetrexed; Drug: Cisplatin

Gemcitabine+Carboplatin

ACTIVE COMPARATOR

Participants receive gemcitabine 1250 mg/m\^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and carboplatin AUC 5 or 6, administered as IV infusion on Day 1 of a 21-day cycle, for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Drug: Carboplatin; Drug: Gemcitabine

Gemcitabine+Cisplatin

ACTIVE COMPARATOR

Participants receive gemcitabine 1250 mg/m\^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and cisplatin 75 mg/m\^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Drug: Cisplatin; Drug: Gemcitabine

Interventions

Pembrolizumab DRUG

Pembrolizumab IV solution

Also known as: MK-3475, SCH 900475, KEYTRUDA®

Pembrolizumab

Paclitaxel DRUG

Paclitaxel IV solution

Paclitaxel+Carboplatin

Carboplatin DRUG

Carboplatin IV solution

Gemcitabine+Carboplatin; Paclitaxel+Carboplatin; Pemetrexed+Carboplatin

Pemetrexed DRUG

Pemetrexed Lyophilized Powder for Infusion

Paclitaxel+Carboplatin; Pemetrexed+Carboplatin; Pemetrexed+Cisplatin

Cisplatin DRUG

Cisplatin IV solution

Gemcitabine+Cisplatin; Pemetrexed+Cisplatin

Gemcitabine DRUG

Gemcitabine Lyophilized Powder for Infusion

Gemcitabine+Carboplatin; Gemcitabine+Cisplatin

Eligibility Criteria

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

You may qualify if:

• Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation, and received no prior systemic chemotherapy treatment for their metastatic NSCLC
• At least one radiographically measurable lesion per RECIST 1.1
• Life expectancy of at least 3 months
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
• Adequate organ function
• No history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
• Provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor at the time of or AFTER the diagnosis of metastatic disease has been made AND from a site not previously irradiated
• PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central laboratory
• Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential
• Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for 120 days after last dose of study drug and up to 180 days after last dose of chemotherapy

You may not qualify if:

• EGFR sensitizing mutation and/or ALK translocation
• Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of study drug
• Tumor specimen is not evaluable for PD-L1 expression by the central laboratory
• Receiving systemic steroid therapy \< 3 days prior to first dose of study drug or receiving any other form of immunosuppressive medication
• Expected to require any other form of systemic or localized antineoplastic therapy during the study
• Received prior systemic cytotoxic chemotherapy, biological therapy, major surgery within 3 weeks of first dose of study drug; received thoracic radiation therapy of \> 30 gray (Gy) within 6 months of first dose of study drug
• Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor \[TNFR\] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in past 2 years
• Allogenic tissue/solid organ transplant
• Interstitial lung disease or pneumonitis that has required oral or IV steroids
• Received or will receive a live vaccine within 30 days prior to first dose of study drug
• Active infection requiring IV systemic therapy
• Known history of human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (10)

• Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR for the KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1 Positive Non-Small-Cell Lung Cancer . N Engl J Med. 2016;[e published 09 Oct 2016]. doi: 10.1056/NEJMoa1606774

  RESULT

• Halmos B, Burke T, Kalyvas C, Insinga R, Vandormael K, Frederickson A, Piperdi B. Indirect comparison of pembrolizumab monotherapy versus nivolumab + ipilimumab in first-line metastatic lung cancer. Immunotherapy. 2022 Apr;14(5):295-307. doi: 10.2217/imt-2021-0273. Epub 2022 Jan 25.

  PMID: 35073727 DERIVED

• Satouchi M, Nosaki K, Takahashi T, Nakagawa K, Aoe K, Kurata T, Sekine A, Horiike A, Fukuhara T, Sugawara S, Umemura S, Saka H, Okamoto I, Yamamoto N, Sakai H, Kishi K, Katakami N, Horinouchi H, Hida T, Okamoto H, Atagi S, Ohira T, Rong Han S, Noguchi K, Ebiana V, Hotta K. First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset. Cancer Sci. 2021 Dec;112(12):5000-5010. doi: 10.1111/cas.15144. Epub 2021 Nov 5.

  PMID: 34543477 DERIVED

• Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score >/= 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. doi: 10.1200/JCO.21.00174. Epub 2021 Apr 19.

  PMID: 33872070 DERIVED

• Satouchi M, Nosaki K, Takahashi T, Nakagawa K, Aoe K, Kurata T, Sekine A, Horiike A, Fukuhara T, Sugawara S, Umemura S, Saka H, Okamoto I, Yamamoto N, Sakai H, Kishi K, Katakami N, Horinouchi H, Hida T, Okamoto H, Atagi S, Ohira T, Han SR, Noguchi K, Ebiana V, Hotta K. First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset. Cancer Sci. 2020 Dec;111(12):4480-4489. doi: 10.1111/cas.14647. Epub 2020 Oct 16.

  PMID: 32926507 DERIVED

• Lala M, Li TR, de Alwis DP, Sinha V, Mayawala K, Yamamoto N, Siu LL, Chartash E, Aboshady H, Jain L. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020 May;131:68-75. doi: 10.1016/j.ejca.2020.02.016. Epub 2020 Apr 15.

  PMID: 32305010 DERIVED

• Bhadhuri A, Insinga R, Guggisberg P, Panje C, Schwenkglenks M. Cost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland. Swiss Med Wkly. 2019 Dec 27;149:w20170. doi: 10.4414/smw.2019.20170. eCollection 2019 Dec 16.

  PMID: 31880807 DERIVED

• van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.

  PMID: 31395089 DERIVED

• Brahmer JR, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. doi: 10.1016/S1470-2045(17)30690-3. Epub 2017 Nov 9.

  PMID: 29129441 DERIVED

• Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.

  PMID: 27718847 DERIVED

Related Links

• Merck Oncology Clinical Trial Information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Paclitaxel; Carboplatin; Pemetrexed; Cisplatin; Gemcitabine

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; 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; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

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

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2014
• First Posted: May 20, 2014
• Study Start: August 25, 2014
• Primary Completion: May 9, 2016
• Study Completion: May 27, 2021
• Last Updated: June 13, 2022
• Results First Posted: July 7, 2017

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share