Martin Reck, MD, PhD, on KEYNOTE-799, LAURA, and the Future of Treatment for Stage III NSCLC

Martin Reck, MD, PhD, of the LungenClinic Grosshansdorf, joined Lung Cancers Today to share insights and updates on treatment for stage III lung cancer from the European Lung Cancer Congress (ELCC) 2025, including KEYNOTE-799 and LAURA.

Dr. Reck spoke about the results from KEYNOTE-799, which he presented during the second proffered paper session of ELCC 2025, explaining that the final analysis showed “very encouraging and robust data” that demonstrated there is “sustainable efficacy for this quite intensive concept of simultaneous chemoimmunoradiotherapy in patients with locally advanced, nonresectable non–small cell lung cancer.”

The final analysis included 5 years of follow-up data on patients who received pembrolizumab plus concurrent chemoradiation therapy (cCRT) for unresectable locally advanced stage III non–small cell lung cancer (NSCLC).

“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,” Dr. Reck said of the concept under investigation in KEYNOTE-799.

In an earlier analysis of KEYNOTE-799, pembrolizumab plus cCRT showed an overall response rate (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.

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 told Lung Cancers Today 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%.”

Patient Characteristics, Methods and End Points in KEYNOTE-799

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 3-week cycle, followed by 2 cycles of pembrolizumab 200 mg once every 3 weeks and carboplatin plus paclitaxel once a week and standard thoracic radiotherapy (TRT). The median time from the first dose to data cutoff on March 19, 2024, was 59.2 months (range, 54.3-64.5 months) in cohort A.

Patients in cohort B (n=102) received 3 cycles of pembrolizumab 200 mg once every 3 weeks with cisplatin plus pemetrexed, with standard TRT in cycles 2 and 3. All patients received 14 additional cycles of pembrolizumab. The median time from the first dose to data cutoff was 54.4 months (range, 43.5-64.2 months) in cohort B.

The primary end points of KEYNOTE-799 were ORR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review and incidence of grade 3 or higher pneumonitis. The secondary end points were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review, overall survival (OS), and safety.

How KEYNOTE-799 and LAURA May Shape the Future of Treatment for Stage III NSCLC

Dr. Reck explained that alongside KEYNOTE-799, the second proffered paper session of the European Lung Cancer Congress 2025 also featured another update on stage III NSCLC: the presentation of updated OS results from the phase 3 LAURA study, which is “exploring a consolidation treatment after chemoradiotherapy.”

Dr. Reck explained that the double-blinded phase 3 study previously showed that treatment with osimeritinib after definitive chemoradiotherapy  significantly prolonged PFS compared with placebo for patients with unresectable stage III EGFR-mutated NSCLC, with a hazard ratio of 0.16 (95% CI, 0.10-0.24; P<0.001), which led to its approval for this population of patients.

“Here at ELCC, we had the first glimpse of the overall survival data that we had from a new data cut…now we indeed do see a trend in improvement in overall survival following the treatment with osimeritinib after chemoradiotherapy in this group of patients with EGFR-mutated stage III non–small cell lung cancer,” Dr. Reck explained.

This regimen represents “clearly a very active as well as tolerable new treatment opportunity that we do have for these patients,” he said.

With trials such as KEYNOTE-799 and LAURA, the treatment landscape for stage III NSCLC is moving into “a very personalized field of therapy,” as has previously occurred in stage IV NSCLC, Dr. Reck explained.

“We have the opportunity to offer more and more patients, even in stage III non–small cell lung cancer, a very effective treatment opportunity and a very attractive perspective to prolong their survival or at least to have a very solid prolongation of the stabilization of their disease,” he said.