Two-year update from KEYNOTE-799: Pembrolizumab plus concurrent chemoradiation therapy (cCRT) for unresectable, locally advanced, stage III NSCLC.

8508 Background: Primary analysis (database cutoff, Oct 28, 2020) of the global KEYNOTE-799 study (NCT03631784) in patients (pts) with unresectable, locally advanced stage III NSCLC, showed that pembrolizumab (pembro; anti–PD-1) plus cCRT resulted in an ORR of 70.5% in cohort A (n = 112; squamous and nonsquamous) and 70.6% in cohort B (n = 102; nonsquamous only) and grade ≥3 pneumonitis in 9 (8.0%) and 7 (6.9%) pts, respectively. We present updated outcomes with 1 y of additional follow-up. Methods: In this nonrandomized, phase 2 study, eligible pts were aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA-C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received carboplatin AUC 6 plus paclitaxel 200 mg/m 2 and pembro 200 mg for one 3-wk cycle, followed by carboplatin AUC 2 plus paclitaxel 45 mg/m 2 QW for 6 wks plus 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous) received 3 cycles of cisplatin 75 mg/m 2 , pemetrexed 500 mg/m 2 , and pembro 200 mg Q3W plus standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Results: Of 216 pts enrolled in this study, 112 in cohort A and 102 in cohort B received treatment. Median (range) time from first dose to database cutoff (Oct 18, 2021) was 30.2 (25.3–35.5) mo in cohort A and 25.4 (14.5–35.2) mo in cohort B. ORR (95% CI) was 71.4% (62.1%–79.6%) in cohort A and 75.5% (66.0%–83.5%) in cohort B. Median duration of response (DOR) and OS were not reached (NR) in both cohorts; median PFS was 30.6 mo in cohort A, and NR in cohort B (Table). ORR was 66.7% in pts with PD-L1 TPS <1% and 77.3% in pts with PD-L1 TPS ≥1% in cohort A and 78.6% and 72.5%, respectively, in cohort B. ORR was similar by histology (squamous, 72.0%; nonsquamous, 74.1%). Grade ≥3 pneumonitis occurred in 16 pts (7.5%) overall; 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Treatment-related grade ≥3 AEs occurred in 64.3% and 51.0% of pts in cohort A and B, respectively. Conclusions: With the accrual of additional responses after >2 y of follow-up, pembro plus cCRT continues to demonstrate robust and durable responses, regardless of PD-L1 TPS and tumor histology, promising survival outcome and manageable safety in pts with previously untreated, locally advanced stage III NSCLC. Clinical trial information: NCT03631784. [Table: see text]