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]

Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review

“…Of those, 56 duplicate studies were excluded. After careful screening and assessment, 11 clinical trials involving 1,113 patients with NSCLC were finally included in the analysis (6,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Figure 1 illustrates the flow diagram of study selection.…”

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Negative Patient With Refractory Metastatic Esophageal Squamous Cell Carcinoma: A Case Report and Literature Review

“…The sequence of radiotherapy combined with ICI is still controversial and the use of ICI after radiotherapy may reduce severe pneumonia just as PACIFIC and PEMBRO-RT study did. But KEYNOTE-799 indicated that chemoradiotherapy and simultaneous ICI were well tolerated, and the incidence of pneumonia above grade 3 was 3.4% (41).…”

Management of Resectable Stage III-N2 Non-Small-Cell Lung Cancer (NSCLC) in the Age of Immunotherapy

“…Presented at the ASCO meeting 2020, the preliminary results, with recruitment yet to be completed, of the phase II, non-randomised trial KEYNOTE-799, with pembrolizumab concomitant to CRT, show that the overall response rate (ORR) was 67% in patients with carboplatin and paclitaxel-based ChT, and 56.6% with platinum and pemetrexed. The percentage of grade 5 pneumonitis was 3.5% with carboplatin + paclitaxel [ 78 ]. Likewise, results have been presented for atezolizumab prior and subsequent to CRT treatment, with an ORR of 82.4% for PD-L1 negative patients and 90.9% for PD-L1 positive.…”