FF-10832 liposomal gemcitabine monotherapy or combination with pembrolizumab in patients with advanced non–small cell lung cancer.

Abstract

8560 Background: FF-10832, a stable liposomal formulation of gemcitabine with a prolonged half-life (mean t 1/2 of 26 hours compared to ~3 hours for gemcitabine HCl), has demonstrated single agent activity in patients (pts) with solid tumors. In pre-clinical models, FF-10832 has yielded superior anti-tumor activity compared to gemcitabine alone and in combination with PD-1 inhibitors. Following a safety run-in, we investigated the clinical activity of FF-10832 in an expansion study, administered alone or in combination with pembrolizumab (PEM), in pts with advanced/metastatic (m) NSCLC (NCT05318573). Methods: In the open-label single arm safety run-in, 40 mg/m 2 FF-10832 and 200 mg PEM every 3 weeks was established as safe and tolerable in 12 pts including 6 mNSCLC patients with unlimited prior therapies. The trial was expanded using this regimen. Pts were randomized to receive FF-10832 alone (mono) or FF-10832 +PEM (combo). Eligibility stipulated up to 3 prior therapies in the advanced/metastatic setting with prior disease progression (PD) on platinum and PD-(L)1-directed therapy. Pts receiving FF-10832 monotherapy could add PEM to FF-10832 upon PD determined by RECIST 1.1. To be evaluable for anti-tumor activity, pts must have had at least one RECIST assessment ≥6 weeks after baseline. All pts were evaluable for safety. Results: A total of 41 NSCLC pts were treated with FF-10832 (N=21) or FF-1032+PEM (N=20); median # of prior therapies was 2 for both arms. RECIST evaluability was achieved in 30 pts (14/16; mono/combo); 11 pts (7/4; mono/combo) came off study before evaluation for anti-tumor activity. No objective responses were observed. Stable disease (SD) was recorded in 9/14 pts in the mono arm and 13/16 in the combo arm; 4 pts (1 mono/3 combo) with >20% tumor shrinkage. Median time on study for the mono and combo arms was 9 (1 – 48.1) and 12.1 (1.1 – 44) weeks, respectively. Median (95% CI) PFS in months: mono arm, 2.7 (1.4 – 4.3); combo arm, 2.8 (1.9 – 5.5). Five mono pts began FF-10832+PEM treatment upon PD, two that remain on combination therapy with SD for 23 and 33 weeks after progressing on FF-10832 monotherapy. Related AEs were similar in mono vs combo arms; those in ≥15% of pts in each arm included nausea, vomiting, fatigue, rash, infusion-related reaction, and anemia. Related grade ≥3 AEs occurred in 33% (mono) and 45% (combo) of pts. The only attributable grade ≥3 events in >1 pt were in the combo arm (n): anemia (3), fatigue (2), dyspnea (2), and lymphopenia (2). FF-10832 PK showed a profile consistent with that previously reported (terminal t 1/2, ~30 hours). Overall survival data are pending. Conclusions: FF-10832 alone or in combination with PEM in platinum-CPI refractory pts proved tolerable with a safety profile matching previous experience. There were no objective responses, but the majority of evaluable pts had SD at 1 st assessment, some with tumor shrinkage. Aggregate mPFS was 2.7 mos. Clinical trial information: NCT05318573 .