1340P - A phase II study of docetaxel (D), ramucirumab (R), and pembrolizumab (P) for pts with metastatic or recurrent non-small cell lung cancer (NSCLC) who progressed on platinum-doublet and PD-1/PD-L1 blockade

Background

NSCLC treatment (trt) efficacy remains modest after progression on platinum and immune checkpoint inhibitors (ICI). Salvage trt with D + R has a 6-month Progression Free Survival (PFS) rate of 37%.

Methods

We conducted a phase 2, single-arm study of D (75mg/m²), R (10mg/kg), P (200mg) given intravenously every 3 weeks until disease progression or severe toxicity. Eligible patients (pts): M/R NSCLC, progressed on concurrent or sequential platinum and ICI, no prior exposure to D or R, ECOG 0-1, measurable disease, adequate organ function. A safety run-in cohort was performed. Simon’s two-stage optimum design was used to evaluate efficacy. The null hypothesis of 6-month PFS rate of 37% was tested against one-sided alternative hypothesis with rate >56% (α 0.1, power 80%). PFS and OS were estimated using Kaplan Meier method.

Results

15 pts have initiated study therapy at the time of submission: 10 (67%) white, 4 (27%) female, 14 (93%) ever-smokers, 13 (87%) adenocarcinoma, 2 (13%) PD-L1 ≥50%, 14 (93%) received platinum + ICI concurrently, 8 (53%) progressed after 6 months (m) on prior ICI, 4 (27%) had brain metastases. Median age was 63 (57-82) years. 14 were evaluable for 6-month PFS rate (primary endpoint). At 6 m of trt, 7 (50%) did not progress, 3 (21.4%) did progress, 3 (21.4%) withdrew without progression. 6-month PFS rate was 74% (95CI, 39-91). Median PFS was 8.3 (95CI, 5.4-NE) m. Median OS was 21.8 (95CI, 8.2-28.3) m with 1-year survival rate of 80% (40.3-94.8). 4 of 13 pts (31%) achieved partial response with 7.8 m median duration of response. Pts who progressed after 6 m on prior ICI had longer median PFS (16.6 vs. 5.6 m; p= 0.04) and OS (22.9 vs. 15.2 m; p= 0.02) compared to pts who progressed within 6 m on prior ICI. Disease control rate at 3-month was 100%. 57% pts went received post-progression therapy. No grade 5 or dose limiting toxicities were observed; grade ≥3 trt-related adverse events: pneumonitis (6%), infusion reaction with cardiac arrest (6%), port infection (6%).

Conclusions

The combination of docetaxel, ramucirumab and pembrolizumab was well tolerated and demonstrated activity that warrants further evaluation in pts with R/M NSCLC.

Clinical trial identification

NCT04340882.

Editorial acknowledgement

Legal entity responsible for the study

Emory University.

Funding

Merck.

Disclosure

B. El Osta: Non-Financial Interests, Institutional, Research Funding: Merck. J. Carlisle: Non-Financial Interests, Institutional, Research Funding: AstraZeneca, Amgen, Parexel, and Hutchinson Medipharama; Financial Interests, Personal, Advisory Board: Sanofi. C. Steuer: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Novocure, AstraZeneca, Merck, Regeneron; Financial Interests, Personal and Institutional, Steering Committee Member: Daiichi Sankyo. M. Dhodapkar: Other, Personal, Advisory Board: Janssen, Sanofi, Lava Therapeutics. T.K. Owonikoko: Non-Financial Interests, Institutional, Research Funding: Novartis, Bayer, Regeneron, AstraZeneca, Amgen, Pfizer, Merck, Roche/Genentech, Cardiff Oncology, Ymabs, Boehringer Ingelheim, and EMD Serono; Other, Personal, Advisory Board: Novartis, Eli Lilly, Eisai, Bristol Myers Squibb, Amgen, AstraZeneca, Boehringer Ingelheim, EMD Serono, XCovery, Bayer, Merck, Oncocyte, Takeda, Jazz, Zentalis, Ipsen, Daiichi Sankyo, Janssen, BeiGene, Genentech, Coherus, GenCART, Heat Biologics, Meryx, and Puma; Other, Personal, Other: EMD Serono; Roche/Genentech, Takeda; Stocks/Ownership Interest: Coherus Biosciences, GenCART/Cambium Oncology, Taobob LLC. S.S. Ramalingam: Financial Interests, Personal, Other, Editor in Chief, CANCER journal: American Cancer Society; Financial Interests, Research Grant: Merck, BMS, GSK; Financial Interests, Research Grant, Coordinating investigator for phase 3 trial: AstraZeneca, Amgen. T.A. Leal: Other, Personal, Advisory Board: GI Therapeutics, Pfizer, Regeneron, Amgen, AstraZeneca, Novocure, Takeda, Merck, and Jazz Pharmaceuticals; Other, Personal, Advisory Role: Catalyst, Eisai, Jazz, Janssen, and F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.