Efficacy Comparison of Dostarlimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)

NCT04581824 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 213403
• Study Type: interventional
• Target: 243
• Locations: 12 countries
• Sites: 58

Brief Summary

NSCLC comprises of approximately 84 percent (%) of all lung cancers and is often diagnosed at advanced stage due to poor prognosis. Dostarlimab is an immunoglobulin G (IgG)4 kappa humanized monoclonal antibody (mAb) that binds with high affinity to programmed cell death protein 1 (PD 1), resulting in inhibition of binding to programmed death ligand 1 (PD L1) and programmed death ligand 2 (PD L2). This study aims to compare the efficacy and safety PD-1 inhibitors dostarlimab and pembrolizumab, when administered in combination with chemotherapy (pemetrexed, cisplatin and carboplatin), in participants with non-squamous NSCLC without a known sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or receptor tyrosine kinase-1 (ROS-1) mutation, BRAF V600E mutation, or other genomic aberration for which an approved targeted therapy is available. A total of approximately 240 participants will be enrolled in the study for a period of 5 years.

Conditions

Lung Cancer, Non-Small Cell

Keywords

Non small cell lung cancer; Dostarlimab; Pembrolizumab; Pemetrexed; Carboplatin; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants who had a confirmed complete response (CR) or confirmed partial response (PR) as their best overall response (BOR) recorded from the date of randomization until disease progression or initiation of new anti-cancer therapy, whichever is earlier based on blinded independent central review (BICR) evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters (e.g., percent change from baseline).

  Up to approximately 20 months

Secondary Outcomes (17)

• Overall Survival (OS)

  Up to approximately 46 months

• Progression-free Survival (PFS)

  Up to approximately 46 months

• Number of Participants With Treatment-emergent Adverse Event (TEAEs), TEAEs Leading to Death and TEAEs Leading to Treatment Discontinuation

  Up to 46 months

• Number of Participants With Treatment Emergent Immune-related Adverse Event (irAE)

  Up to 46 months

• Number of Participants With Serious AEs

  Up to approximately 46 months

Study Arms (2)

Participants receiving dostarlimab plus chemotherapy

EXPERIMENTAL

Participants will receive dostarlimab on Day 1 of every 21 Day cycle followed by pemetrexed, and then followed by cisplatin or carboplatin (Cycles 1 to 4 only) as per investigator decision.

Drug: Dostarlimab; Drug: Chemotherapy

Participants receiving pembrolizumab plus chemotherapy

ACTIVE COMPARATOR

Participants will receive pembrolizumab on Day 1 of every 21 Day cycle followed by pemetrexed, and then followed by cisplatin or carboplatin (Cycles 1 to 4 only) as per investigator decision.

Drug: Pembrolizumab; Drug: Chemotherapy

Interventions

Dostarlimab DRUG

Dostarlimab will be administered through a 30 minute infusion at a dose of 500 milligrams (mg) intravenously (IV) every 3 weeks (Q3W) up to a maximum of 35 cycles (each cycle of 21 days).

Participants receiving dostarlimab plus chemotherapy

Pembrolizumab DRUG

Pembrolizumab will be administered through a 30 minute infusion at a dose of 200 mg Q3W up to a maximum of 35 cycles (each cycle of 21 days).

Participants receiving pembrolizumab plus chemotherapy

Chemotherapy DRUG

Pemetrexed will be administered at 500 milligram per meter square (mg/m\^2 ) IV through a 10 minute IV infusion Q3W, up to a maximum of 35 cycles (each cycle of 21 days). Cisplatin will be administered at 75 mg/m\^2 through a 30 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision. Carboplatin will also be administered at area under the concentration time curve 5 milligram/milliliters/minute (mg/mL/min) (maximum dose: 750 mg) through a 15 to 60 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision.

Participants receiving dostarlimab plus chemotherapy; Participants receiving pembrolizumab plus chemotherapy

Eligibility Criteria

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

You may qualify if:

• Participant must be greater than equal to (\>=) 18 years old, must be able to understand the study procedures, and agrees to participate in the study by providing written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Participant has histologically- or cytologically-confirmed metastatic non-squamous NSCLC with documented absence of a sensitizing EGFR, ALK, ROS-1, or BRAFV600E mutation or other genomic aberration for which an approved targeted therapy is available. Mixed tumors will be categorized by the predominant cell type; if the tumor has predominantly squamous cell histology or if small cell elements are present, the participant is ineligible.
• Participants must have measurable disease, that is (i.e.) presenting with at least 1 measurable lesion per RECIST v1.1 as determined by the local site Investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions and if there are other target lesions. If there is only 1 target lesion that was previously irradiated, the participant is not eligible.
• Participant has documented PD L1 status by the 22C3 pharmDx assay (Agilent/Dako). If no prior PD L1 result is available at the time of Screening, the participant can be tested locally using the stated method, or central PD L1 testing can be completed. Results are needed for stratification and must be available prior to randomization.
• Participant has an ECOG performance status score of 0 or 1.
• Participant has a life expectancy of at least 3 months.
• Participant has adequate organ function.
• Participant has recovered to Grade less than equal to (\<=)1 from any prior treatment related toxicities at the time of randomization. A participant with Grade 2 alopecia is an exception to this criterion and may qualify for this study.
• Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants are eligible to participate if they agree to the following during the Treatment Period and for at least 150 days after the last dose of study treatment:
• Refrain from donating sperm plus, either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
• Must agree to use contraception/barrier as follows:
• Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
• Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.

You may not qualify if:

• Participant has received prior systemic therapy for the treatment of metastatic NSCLC. Participants who have received neoadjuvant or adjuvant chemotherapy are eligible if the neoadjuvant/adjuvant therapy was completed at least 12 months prior to the development of metastatic disease.
• Participant has received prior therapy with a PD (L)1 or PD L2 inhibitor, a cytotoxic T lymphocyte associated protein 4 (CTLA 4) inhibitor, a T cell immunoglobulin and mucin domain containing 3 (TIM 3) inhibitor, or any other immunotherapy agent (eg, OX40) for the treatment of cancer.
• Participant has received radiation to the lung that is \>30 Gray (Gy) within 6 months of the first dose of study treatment.
• Participant has completed palliative radiotherapy within 7 days of the first dose of study treatment.
• Participant is ineligible if any of the following hepatic characteristics are present:
• Alanine aminotransferase (ALT) \>2.5 times upper limit of normal (ULN) without liver metastases/tumor infiltration.
• ALT \>5 times ULN with liver metastases/tumor infiltration.
• Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%)
• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per Investigator assessment)
• Participant has a corrected QT interval (QTc) \>450 milliseconds (msec) (or QTc \>480 msec for participants with bundle branch block).
• Participant has an additional malignancy or a history of prior malignancy, with the exception of adequately treated basal or squamous skin cancer, cervical carcinoma in situ, or bladder carcinoma in situ without evidence of disease, or had a malignancy treated with curative intent and with no evidence of disease recurrence for 5 years since the initiation of that therapy.
• Participant has known active brain metastases and/or leptomeningeal metastases. Participants who have received prior therapy for their brain metastases and have radiographically stable central nervous system disease may participate, provided they are neurologically stable for at least 2 weeks before study entry and must be off corticosteroids within 3 days prior to the first dose of study treatment. Stable brain metastases by this definition should be established prior to the first dose of study treatment. Participants with known untreated, asymptomatic brain metastases (i.e., no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesions \>1.5 centimeters \[cm\]) may participate, but will require regular imaging of the brain as a site of disease.
• Participant has tested positive for the presence of hepatitis B surface antigen or has a positive hepatitis C antibody test result at Screening, or within 3 months prior to first dose of study treatment. For potent immunosuppressive agents, participants who test positive for the presence of hepatitis B core antibody should also be excluded.
• Participant has an active infection requiring systemic therapy within 1 week prior to the anticipated first dose of study treatment.
• Participant has known human immunodeficiency virus (HIV) (positive for HIV 1 or HIV 2 antibodies).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (58)

GSK Investigational Site

Denver, North Carolina, 80128, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45242, United States

Location

GSK Investigational Site

Fairfax, Virginia, 22031, United States

Location

GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aire, C1012AAR, Argentina

Location

GSK Investigational Site

Córdoba, X5004FHP, Argentina

Location

GSK Investigational Site

Florida, 1602, Argentina

Location

GSK Investigational Site

La Plata, 1900, Argentina

Location

GSK Investigational Site

La Rioja, F5300COE, Argentina

Location

GSK Investigational Site

Pergamino, B2700CPM, Argentina

Location

GSK Investigational Site

Rosario, S2000KZE, Argentina

Location

GSK Investigational Site

San Juan, J5402DIL, Argentina

Location

GSK Investigational Site

Viedma, R8500ACE, Argentina

Location

GSK Investigational Site

Barretos, 14784-400, Brazil

Location

GSK Investigational Site

Fortaleza, 60336-232, Brazil

Location

GSK Investigational Site

Natal, 59075-740, Brazil

Location

GSK Investigational Site

Rio de Janeiro, 20230 -130, Brazil

Location

GSK Investigational Site

São Paulo, 04014-002, Brazil

Location

GSK Investigational Site

Vitória, 29043-260, Brazil

Location

GSK Investigational Site

Santiago, 7500653, Chile

Location

GSK Investigational Site

Santiago, 8320000, Chile

Location

GSK Investigational Site

Caen, 14033, France

Location

GSK Investigational Site

Le Mans, 72000, France

Location

GSK Investigational Site

Limoges, 87042, France

Location

GSK Investigational Site

Pessac, 33604, France

Location

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Valenciennes, 59300, France

Location

GSK Investigational Site

Berlin, 12200, Germany

Location

GSK Investigational Site

Cologne, 51109, Germany

Location

GSK Investigational Site

Frankfurt, 60488, Germany

Location

GSK Investigational Site

Immenhausen, 34376, Germany

Location

GSK Investigational Site

Oldenburg, 26121, Germany

Location

GSK Investigational Site

Aviano PN, 33081, Italy

Location

GSK Investigational Site

Brescia, 25123, Italy

Location

GSK Investigational Site

Milan, 20133, Italy

Location

GSK Investigational Site

Milan, 20141, Italy

Location

GSK Investigational Site

Napoli, 80131, Italy

Location

GSK Investigational Site

Roma, 00152, Italy

Location

GSK Investigational Site

Bydgoszcz, 85-796, Poland

Location

GSK Investigational Site

Lodz, 90-338, Poland

Location

GSK Investigational Site

Lublin, 20-954, Poland

Location

GSK Investigational Site

Olsztyn, 10-357, Poland

Location

GSK Investigational Site

Poznan, 60-693, Poland

Location

GSK Investigational Site

Bucharest, 030442, Romania

Location

GSK Investigational Site

Craiova, 200347, Romania

Location

GSK Investigational Site

Floreşti, 407280, Romania

Location

GSK Investigational Site

Cheongju Chungcheongbuk-do, 28644, South Korea

Location

GSK Investigational Site

Pusan, 48108, South Korea

Location

GSK Investigational Site

Seoul, 05505, South Korea

Location

GSK Investigational Site

Seoul, 06351, South Korea

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Barcelona, 08003, Spain

Location

GSK Investigational Site

Jaén, 23007, Spain

Location

GSK Investigational Site

Lugo, 27003, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Seville, 41014, Spain

Location

GSK Investigational Site

Changhua, 500, Taiwan

Location

GSK Investigational Site

Taipei, 11490, Taiwan

Location

Related Publications (3)

• Austin D, Melhem M, Gandhi Y, Lu S, Visser S. Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. CPT Pharmacometrics Syst Pharmacol. 2023 Jan;12(1):87-94. doi: 10.1002/psp4.12878. Epub 2022 Nov 16.

  PMID: 36317409 BACKGROUND

• Lim SM, Peters S, Ortega Granados AL, Pinto GDJ, Fuentes CS, Lo Russo G, Schenker M, Ahn JS, Reck M, Szijgyarto Z, Huseinovic N, Zografos E, Buss E, Stjepanovic N, O'Donnell S, de Marinis F. Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial. Nat Commun. 2023 Nov 11;14(1):7301. doi: 10.1038/s41467-023-42900-4.

  PMID: 37951954 BACKGROUND

• Lim SM, Ortega Granados AL, Pinto GDJ, Fuentes CS, Lo Russo G, Schenker M, Ahn JS, de Marinis F, Locke K Jr, Szijgyarto Z, Buss E, Stjepanovic N, Diaz-Padilla I, Peters S. Long-term Survival Analysis From PERLA, A Phase II Randomized Trial of Dostarlimab With Chemotherapy Versus Pembrolizumab With Chemotherapy in Metastatic Nonsquamous NSCLC. JTO Clin Res Rep. 2025 Sep 4;6(10):100900. doi: 10.1016/j.jtocrr.2025.100900. eCollection 2025 Oct.

  PMID: 41080090 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

dostarlimab; pembrolizumab; Drug Therapy

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)

Therapeutics

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Participants and study staff may only be blinded to study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: October 9, 2020
• Study Start: November 19, 2020
• Primary Completion: August 4, 2022
• Study Completion: September 10, 2024
• Last Updated: August 8, 2025
• Results First Posted: September 18, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

PL (5); TW (2); BR (6); AR (10); DE (5); IT (6); FR (6); US (3); RO (3); ES (5); KR (5); CL (2)