KEYNOTE-799 Final Analysis Shows Regimen Has ‘Sustainable Efficacy’ in NSCLC

Pembrolizumab plus concurrent chemoradiation therapy (cCRT) “continued to demonstrate antitumor activity” in patients with unresectable locally advanced stage III non-small cell lung cancer (NSCLC) after five years of follow-up, according to the final analysis of KEYNOTE-799.

Martin Reck, MD, PhD, of the LungenClinic Grosshansdorf, presented the final analysis during the second proffered paper session of the European Lung Cancer Congress 2025 in Paris, France.

“Overall, these are very encouraging and robust data showing sustainable efficacy for this quite intensive concept of simultaneous chemoimmunoradiotherapy in patients with locally advanced, nonresectable non-small cell lung cancer,” Dr. Reck told Lung Cancers Today in an interview.

In an earlier analysis of KEYNOTE-799, pembrolizumab plus cCRT showed an ORR of 71.4% in cohort A, which included patients with squamous and nonsquamous NSCLC. The combination showed an ORR of 74.5% in cohort B, which included only patients with nonsquamous NSCLC.

“We now have the five-year follow-up data for this new concept,” Dr. Reck said in an interview. “The idea is to move the immunotherapy from the consolidation part to the active chemoradiation part in order to enhance the immunogenic reaction of our treatment.”

The study included adults with untreated, unresectable stage IIIA–C NSCLC. Patients in cohort A (n=112) received pembrolizumab 200 mg and carboplatin plus paclitaxel for a single three-week cycle, followed by two cycles of pembrolizumab 200 mg once every three weeks and carboplatin plus paclitaxel once a week and standard thoracic radiotherapy (TRT). The median time from the first dose to data cutoff of March 19, 2024, was 59.2 months (range, 54.3-64.5 months) in cohort A.

In cohort B (n=102), patients received three cycles of pembrolizumab 200 mg once every three weeks with cisplatin plus pemetrexed, with standard TRT in cycles two and three. All patients received 14 additional cycles of pembrolizumab. In cohort B, the median time from the first dose to data cutoff was 54.4 months (43.5-64.2).

The primary endpoints of KEYNOTE-799 were ORR per RECIST v1.1 by blinded independent central review and incidence of grade 3 or higher pneumonitis. The secondary endpoints were PFS per RECIST v1.1 by blinded independent central review, overall survival (OS), and safety.

The 5-year follow-up analysis showed that the ORR was 71.4% (95% CI, 62.1%–79.6%) in cohort A and 75.5% (95% CI, 66.0%–83.5%) in cohort B.

“We had a medium progression-free survival that was between 29 and 45 months,” Dr. Reck said in an interview. “More importantly, when we look at the landmark analysis, the 4-year progression-free survival rates were in the range between 39% and 42%… The median overall survival was between 35.6 and 56.7 months, with a 4-year overall survival rate of 40% to 75%.”

Grade 3 or higher pneumonitis was reported in nine patients (8%) in cohort A and seven patients (6.9%) in cohort B, with grade 3 or higher treatment-related adverse events (AEs) occurring in 73 patients (65.2%) in cohort A and in 52 patients (51%) in cohort B. Around one-third (33.9%) of patients in cohort A discontinued any drug due to treatment-related AEs, compared with 20.9% of those in cohort B.  Immune-mediated AEs and infusion reactions were reported in 52.7% of patients in cohort A and 45.1% of patients in cohort B, with 17.9% and 8.8% being grade 3 or higher, respectively.

Based on the findings from KEYNOTE-799, Dr. Reck explained that the regimen is “clearly a concept which should be evaluated in a phase 3 trial,” noting that this is taking place in the KEYLYNK-012 trial, which has completed recruitment.

“We are waiting for the final readout of this trial,” he explained.

Reference

Reck M, Frost N, Breder V, et al. Pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in unresectable locally advanced non-small cell lung cancer (NSCLC): Final analysis of KEYNOTE-799. Abstract #186O. Presented at the European Lung Cancer Congress 2025, March 26-29; Paris, France.