Phase II study of pembrolizumab (pembro) plus platinum doublet chemotherapy and radiotherapy as first-line therapy for unresectable, locally advanced stage III NSCLC: KEYNOTE-799.

Abstract

9008 Background: KEYNOTE-799 (NCT03631784) evaluates pembro plus concurrent chemoradiation therapy (CCRT) in pts with unresectable, locally advanced stage III NSCLC. Methods: In this phase 2, nonrandomized, open-label trial, pts with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease (RECIST 1.1) received up to 17 cycles of pembro 200 mg Q3W starting with cycle 1 plus standard thoracic radiotherapy (60 Gy in 30 daily 2-Gy fractions) in cycles 2–3 and investigator’s choice of paclitaxel 200 mg/m2 + carboplatin AUC 6 Q3W for cycle 1, then paclitaxel 45 mg/m2 + carboplatin AUC 2 QW for cycles 2–3 (cohort A), or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W (nonsquamous only) in cycles 1–3 (cohort B). Primary endpoints were ORR (CR/PR per RECIST 1.1 by blinded independent central review) and rate of grade ≥3 pneumonitis (per NCI CTCAE v4.0). CIs were estimated using the Clopper-Pearson method. Safety was assessed in all treated patients; efficacy was assessed in pts with ≥15 wks follow-up. Results: As of Jan 3, 2020, 112 and 73 pts have been enrolled in cohorts A and B, respectively; 63 in cohort A and 52 in cohort B continue on treatment. Median (range) follow up was 8.3 (0.7–14.0) mo in cohort A and 5.8 (0.2–13.7) mo in cohort B. ORR (90% CI) was 67.0% (58.9%–74.3%) in cohort A and 56.6% (44.4%–68.2%) in cohort B (Table). Grade ≥3 pneumonitis occurred in 9 pts (8.0%; 90% CI, 4.3%–13.6%) in cohort A and 4 pts (5.5%; 90% CI, 1.9%–12.1%) in cohort B. Treatment-related grade ≥3 AEs occurred in 72 pts (64.3%) in cohort A and 30 pts (41.1%) in cohort B. 4 pts had treatment-related grade 5 pneumonitis (all in cohort A). Enrollment is complete for cohort A and ongoing in cohort B. Conclusions: Pembro plus CCRT shows promising antitumor activity in pts with unresectable, locally advanced stage III NSCLC. Toxicity was as anticipated with pembro plus CCRT. Clinical trial information: NCT03631784. [Table: see text]