A phase 2 study of docetaxel (D), ramucirumab (R), and pembrolizumab (P) for patients with metastatic or recurrent non–small cell lung cancer (NSCLC) who progressed on platinum-doublet and PD-1/PD-L1 blockade.

Abstract

8594 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/m 2 ), R (10mg/kg), P (200mg) given intravenously in 21-day cycles until disease progression or unacceptable toxicity. Eligibility: metastatic or recurrent NSCLC, progression 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 followed by efficacy evaluation using Simon’s two-stage design. The null hypothesis (H 0 ) of 6-month PFS rate of 37% was tested against a one-sided alternative hypothesis with a rate >62% (α 0.1, power 80%). H 0 will be rejected if ≥11 of 21 patients (pts) remain free of progression or death by 6 months (m) with planned sample size of 30 to accommodate early dropout. PFS and overall survival (OS) were estimated using Kaplan Meier method. Results: 30 pts were enrolled. Median (range) age = 66.5 (57-84) years. 20 (67%) were white, 11 (37%) female, 25 (83%) ever-smoker, 23 (77%) non-squamous, 23 (77%) PD-L1 <50%, 29 (97%) received platinum + ICI concurrently, 19 (63%) progressed after 6m on prior ICI, 10 (33%) had brain metastases (mets), and 7 (23%) had liver mets. 28 pts completed at least one cycle of trt: 22 were evaluable for 6-month PFS (primary endpoint), 6 early dropouts <6m on trt w/o progression (including 1 prior to first imaging). No dose limiting toxicities were observed in the first month on trt. 14 (64%) of 22 pts were free of progression by 6m. Median PFS = 7.3m (95CI, 5.6-9.9); median OS = 15m (95CI, 8.4-18.9); ORR = 37%; 10 partial responses; median duration of response = 5.9m (95CI, 1.6-7.2); disease control rate = 96%; clinical benefit = 67%. Nine (31%) pts had trt-related serious adverse event (trSAE) including 1 (3%) death (Table 1). Median (range) cycles for D, R, P were 6 (1-11), 8 (1-23), 8 (1-23), respectively. Two pts remain on trt. Number of D cycles was associated with improved OS (HR 0.73; p = 0.01) and PFS (HR 0.83; p = 0.01). Presence of brain or liver mets (HR 3.13; p = 0.03) and progression in <3m on prior ICI (HR 5.42; p = 0.02) were associated with shorter OS. Conclusions: The study met its primary endpoint and demonstrated a manageable safety profile and a promising efficacy of this regimen. Clinical trial information: NCT04340882 . Summary of trSAE (n= 29). Lethargy / weakness 3 (10%) Pneumonia 3 (10%) Atrial Fibrillation 2 (7%) Dehydration / volume depletion 2 (7%) Low K/Mag 2 (7%) Neutropenia 2 (7%) Death 1 (3%) Diverticulitis 1 (3%) Fever 1 (3%) Interstitial nephritis 1 (3%) Infusion reaction with cardiac arrest 1 (3%) Neutropenic fever 1 (3%) Pancreatic fistula 1 (3%) Pancreatitis 1 (3%) Port infection 1 (3%) Pneumonitis 1 (3%) Septic shock 1 (3%)