1330P - Phase II study of pembrolizumab (pemb) plus plinabulin (plin) and docetaxel (doc) for patients (pts) with metastatic NSCLC after failure on first-line immune checkpoint inhibitor alone or combination therapy: Initial efficacy and safety results on Immune Re-sensitization

Background

Immune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of NSCLC. Once progressed, it is not recommended to continue using ICI monotherapy, and the effect of chemotherapy is limited (ORR ∼10% with doc), so there is a high unmet need. Plin is a selective immunomodulating microtubule-binding agent which promotes dendritic cell maturation and enhances anti-tumor T cell response, and have the potential to overcome immunotherapy resistance. This phase 2 study was aimed to evaluate the efficacy and safety of pemb plus plin and doc in pts with metastatic NSCLC who had progressed after ICI.

Methods

In this investigator-initiated, single-arm, open-label, phase 2 trial, metastatic NSCLC pts who acquired resistance after ICI treatment were enrolled. Participants received pemb 200 mg D1, plin 30 mg/m² D1 and doc 75 mg/m² D1 intravenously for a 21-day cycle. The primary endpoint was investigator-assessed ORR per RECIST 1.1. The secondary endpoints included PFS, OS, DoR and toxicity. The study intends to enroll 47 patients with a formal interim analysis at 19 patients enrolled.

Results

29 pts were enrolled and 19 pts in the first stage were analyzed at database cut on 4/29/2024. Median follow-up was 8.67 months (M) and median age was 66.4 (50-76) years with 68.4% male and 31.6% female. 57.9% were current or former smokers. Histology included 52.6% with adenocarcinoma, 47.4% with squamous cell carcinoma. Confirmed ORR was 21.1%. DCR was 89.5% (defined as PR and SD > 4 M), median PFS was 8.63 M (current 6 M PFS rate was 67.1%, 12 M PFS rate was 49.2%), OS had not been reached (no deaths were reported), and median DoR was 11.40 M. 52.6% of pts experienced G3 or higher treatment-related AEs. There were no treatment-related deaths.

Conclusions

Pemb plus plin and doc in pts with metastatic NSCLC who experienced progressive disease after clinical benefit to ICI was associated with prolonged PFS and DCR compared with historical controls of chemotherapy, with tolerable safety. Clinical trial information: NCT05599789.

Clinical trial identification

Protocol ID K2506; NCT05599789, Initial release:10/26/2022, Last release: 03/24/2024.

Editorial acknowledgement

Legal entity responsible for the study

Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science.

Funding

National High Level Hospital Clinical Research Funding (2022-PUMCH-B-106), Merck Sharp & Dohme LLC (China) & BeyondSpring Pharmaceuticals Inc.

Disclosure

Y. Xu: Financial Interests, Institutional, Funding: AstraZeneca. All other authors have declared no conflicts of interest.