186O - Pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in unresectable locally advanced non-small cell lung cancer (NSCLC): Final analysis of KEYNOTE-799

Background

In the KEYNOTE-799 study of patients (pts) with untreated unresectable locally advanced stage III NSCLC, pembro plus cCRT demonstrated an ORR of 71.4% in cohort A (squamous and nonsquamous) and 74.5% in cohort B (nonsquamous only). We present results from the final analysis based on ∼5 y of follow-up.

Methods

Eligible pts (aged ≥18 y) had untreated unresectable stage IIIA–C NSCLC. Pts in cohort A (squamous or nonsquamous) received pembro 200 mg and carboplatin plus paclitaxel for one 3-wk cycle, then 2 cycles of pembro 200 mg Q3Wand carboplatin plus paclitaxel QWand standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of pembro 200 mg Q3W with cisplatin plus pemetrexed, with standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro. Primary endpoints were ORR per RECIST v1.1 by BICR and incidence of grade ≥3 pneumonitis; secondary endpoints were PFS per RECIST v1.1 by BICR, OS, and safety.

Results

Median (range) time from first dose to data cutoff (March 19, 2024) was 59.2 (54.3–64.5) mo in cohort A (n = 112) and 54.4 (43.5–64.2) mo in cohort B (n = 102). ORR (95% CI) was 71.4% (62.1%–79.6%) in cohort A and 75.5% (66.0%–83.5%) in cohort B (Table). Secondary endpoints (PFS and OS) and duration of response are shown in the table. Grade ≥3 pneumonitis occurred in 9 pts (8.0%) in cohort A and 7 pts (6.9%) in cohort B. Grade ≥3 treatment-related AEs occurred in 73 pts (65.2%) in cohort A and 52 pts (51.0%) in cohort B; 38 pts (33.9%) and 21 pts (20.6%), respectively, discontinued any drug due to treatment-related AEs. Immune-mediated AEs and infusion reactions occurred in 59 pts (52.7%) in cohort A and 46 pts (45.1%) in cohort B, with 20 (17.9%) and 9 (8.8%), respectively, of grade ≥3.Table I860

+No progressive disease by time of last assessment.

Conclusions

Pembro plus cCRT continued to demonstrate antitumor activity after ∼5 y of follow-up, and safety was manageable in patients with unresectable locally advanced stage III NSCLC.

Clinical trial identification

NCT03631784.

Editorial acknowledgement

Medical writing assistance was provided by Aisling Towell, PhD, of ICON plc (Dublin, Ireland). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

M. Reck: Financial Interests, Personal, Other, Personal Fees: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, BeiGene, Daiichi Sankyo, GSK, Eli Lilly, Merck, Mirati, MSD, Novartis, Regeneron, Roche, Pfizer. K.H. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Lilly, MSD, Pfizer; Financial Interests, Personal, Research Grant: Merck Serono and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. N. Frost: Financial Interests, Personal, Other, Speaker’s fee, honoraria for advisory boards, and clinical research funding: AbbVie, Amgen, AstraZeneca, BeiGene, Berlinchemie, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Eli Lilly, Merck Serono, MSD, Novartis, Pfizer, Roche, Sanofi, Regeneron, Takeda; Financial Interests, Personal, Research Grant: Roche. V. Breder: Financial Interests, Personal, Invited Speaker, payment for lectures: Roche, AstraZeneca, Eisai, Bayer, Novartis. D.M. Kowalski: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, MSD, Pfizer, Takeda, Medison, Johnson & Johnson, Amgen, Merck KGaA. N. Reguart: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Boehringer Ingelheim, Pfizer, Novartis, Sanofi, Janssen, AstraZeneca, Amgen, Novartis, AbbVie, Summit Therapeutics; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS, Amgen, Novartis, Sanofi, Merck, PharmaMar, Johnson & Johnson; Financial Interests, Personal, Expert Testimony: Merck, Janssen; Non-Financial Interests, Personal, Principal Investigator, PI of Investigator Initiated Trial (PEERS) sponsored by MSD: MSD. A. Martinez-Marti: Financial Interests, Personal, Advisory Board, Speaker’s Bureau: Bristol Myers Squibb, F. Hoffmann La Roche AG, Merck Sharp & Dohme, MSD Oncology, AstraZeneca/MedImmune; Financial Interests, Personal, Other, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker, And Local PI: AstraZeneca/MedImmune; Financial Interests, Personal, Invited Speaker: F. Hoffmann-La Roche AG, Bristol Myers Squibb, Merck Sharp & Dohme, MSD Oncology; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca/MedImmune, F. Hoffmann-La Roche AG, Bristol Myers Squibb, Merck Sharp & Dohme, MSD Oncology. B. Houghton: Financial Interests, Institutional, Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, to support study conduct. J. Paoli: Financial Interests, Personal, Research Grant: MSD Oncology, BMS, AstraZeneca, Pfizer; Financial Interests, Personal, Other, Travel and accommodation expenses: AstraZeneca, MSD, Pfizer, Ipsen, Roche, Sanofi, Janssen-Cilag, Boehringer Ingelheim, BMS, Amgen. H. Liu: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway. V. Novinskiy: Financial Interests, Personal, Full or part-time Employment: MSD (UK) Limited; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A. Samkari: Financial Interests, Personal, Full or part-time Employment: Global Clinical Development, a subsidiary of Merck & Co., Inc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway. S. Jabbour: Financial Interests, Personal, Advisory Role: MSD, Radialogica, IMX Medical, Lantern DSMC, AstraZeneca, BeiGene, Deichert LLC; Financial Interests, Institutional, Research Grant: MSD, NCI, BeiGene, Guardant, Adlai Nortye. All other authors have declared no conflicts of interest.