Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With Tyrosine Kinase Inhibitor- (TKI)-Resistant Epidermal Growth Factor Receptor- (EGFR)-Mutated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-789/KEYNOTE-789)
CompletedPhase 3Results postedLast updated 22 November 2024
What this trial tests
Phase 3 trial testing pembrolizumab in Non-small Cell Lung Cancer in 492 participants. Completed in 2 October 2023.
18 and older, any sex, with Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)Primary· Up to ~40 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PFS was assessed by blinded independent central review (BICR) using RECIST 1.1. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. The PFS presented was analyzed using the product-limit (Kaplan-Meier) method for censored
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
5.6
5.5 – 5.8
Placebo + Pemetrexed + Chemo
5.5
5.4 – 5.6
Overall Survival (OS)Primary· Up to ~51 months
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
15.9
13.7 – 18.8
Placebo + Pemetrexed + Chemo
14.7
12.7 – 17.1
Objective Response Rate (ORR) Per RECIST 1.1Secondary· Up to ~51 months
ORR was assessed by BICR using RECIST 1.1. ORR is defined as the percentage of participants in the analysis population who experience a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR for participants is presented.
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
29.0
23.4 – 35.1
Placebo + Pemetrexed + Chemo
27.1
21.7 – 33.1
Duration of Response (DOR) Per RECIST 1.1Secondary· Up to ~51 months
DOR was assessed by BICR using RECIST 1.1. For participants who experience a response of CR or PR, DOR is defined as the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first. The DOR presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
6.3
5.9 – 8.3
Placebo + Pemetrexed + Chemo
5.6
4.4 – 6.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined ScoreSecondary· Baseline and Week 18
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
-0.46
-3.17 – 2.25
Placebo + Pemetrexed + Chemo
-2.05
-4.74 – 0.64
Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or DyspneaSecondary· Baseline and up to ~51 months
TTD is the time from baseline to first onset of 10 points or more deterioration from baseline with confirmation by the subsequent visit of 10 points or more deterioration from baseline in the composite endpoint of cough \[EORTC QLQ-Lung Cancer Module 13 (LC13) Item 1; How much did you cough?\], chest pain \[EORTC QLQ-LC13 Item 10; Have you had pain in your chest?\], or dyspnea \[EORTC QLQ-C30 Item 8; Were you short of breath?\]. Individual responses are given on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating a better outcome. The TTD was analyzed using the product-l
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
NA
10.05 – NA
Placebo + Pemetrexed + Chemo
17.97
6.67 – NA
Percentage of Participants Who Experienced an Adverse Event (AE)Secondary· Up to ~44 months
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who experienced an AE is presented.
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
97.6
Placebo + Pemetrexed + Chemo
98.0
Percentage of Participants Who Discontinued Study Treatment Due to AEsSecondary· Up to ~41 months
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who discontinued study treatment due to an adverse event is presented.
Group
Value
95% CI
Pembro + Pemetrexed + Chemo
19.2
Placebo + Pemetrexed + Chemo
17.1
Adverse events — posted to ClinicalTrials.gov
Time frame: Death and Adverse Events up to ~59 months..
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Pembro + Pemetrexed + Chemo
Serious: 86/245 (35%)
Deaths: 219/245
Placebo + Pemetrexed + Chemo
Serious: 70/246 (28%)
Deaths: 186/247
Placebo + Pemetrexed + Chemo Switched Over to Pembro Monotherapy
The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib \[TAGRISSO®\] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status.
The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS.
Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
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Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Merck Sharp & Dohme LLC
Last refreshed: 22 November 2024
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03515837.