1324P - Durvalumab in treatment-naive, stage IV non-small cell lung cancer (NSCLC) patients (pts), with ECOG performance status (PS) 2-3 and high PD-L1 tumour expression: Results of IFCT-1802 SAVIMMUNE phase II trial

Background

PS2-3 is a prognostic factor associated with poor survival and higher incidence of chemotherapy-related adverse events (AE), while the impact of poor PS on immunotherapy (IO) safety and efficacy is less documented. We sought to prospectively assess front-line durvalumab in PS2-3 pts with advanced NSCLC and high PD-L1 expression.

Methods

In this single-arm, multicenter, phase II trial, PS2-3 pts with metastatic ALK-/EGFRwt NSCLC, PD-L1 positive (TPS ≥25%), without brain metastases, received 1500 mg durvalumab every 4 weeks until progression or toxicity. Primary endpoint was safety defined as the incidence of grade ≥3 treatment-related AE (TRAE) during the first 8 weeks (NCI CTCAE v.5.0). Using a 2-step binomial proportion test (O’Brien-Fleming’s procedure), 67 pts were to be included, to achieve 95% power, with 5% type I error rate, to observe <40% (H0) G3-5 events. Secondary objectives included intent-to-treat blinded independent centrally reviewed (BICR) objective response rate (ORR) and progression-free survival (PFS), median duration of response (DoR), overall survival (OS) and PS improvement at 8 weeks.

Results

Overall, 50 pts (median age 68 yrs, PS2 n=40; PS3 n=10) were enrolled between Oct 2020 and Jul 2023. The trial was stopped due to slow accrual. Median follow-up was 15.7 months. Median number of cycles was 3 (1-26). Grade ≥3 TRAE during the first 8 weeks occurred in 10% of pts (95% CI 1.7%–18.3%). No grade 5 TRAE were reported. BICR ORR at 8 weeks (partial responses only) was 26% (95% CI 13.8%–38.2%) and 24% (95% CI 12.2%–35.8%) were confirmed at 16 weeks. Median DoR was 11.3 months (95% CI, 6.4 to NR). Median PFS was 2.3 months (95% CI 1.7–5.6). Median OS was 6.9 months (95% CI 3.9–31.1) with a 40% (95% CI 26. 1–53.7) 12-month OS rate. Median OS in PS2 pts was 9.7 months (95% CI 4.4-NR) and in PS3 pts was 3.0 months (95% CI 0.2-5.6). 12 (44%) of 27 pts with evaluable PS at 8 weeks of durvalumab treatment (95% CI, 25.7%-63.2%) had improved PS (p= 0.01).

Conclusions

In PS2-3 pts with advanced NSCLC and high PD-L1 expression (TPS ≥25%), front-line durvalumab is safe and showed interesting activity. Patient Reported Outcomes will be presented at the meeting.

Clinical trial identification

EudraCT 2018-004742-42.

Editorial acknowledgement

Legal entity responsible for the study

Intergroupe Francophone de Cancérologie Thoracique (IFCT).

Funding

AstraZeneca France + Intergroupe Francophone de Cancérologie Thoracique (IFCT).

Disclosure

V. Gounant: Financial Interests, Personal, Advisory Board: BMS, Takeda, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: BMS, Sanofi, Roche. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, Roche, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi. C. Mascaux: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, MSD, Amgen; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, Kephren, Janssens, Takeda, Sanofi, Novartis. D. Debieuvre: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Janssen, Sanofi-Winthrop, Amgen, Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Coordinating PI: Pfizer; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Janssen, MSD, Pfizer, BMS, Lilly, Boehringer Ingelheim, GSK, Chugaï, Chiesi, Takeda, Bayer, Sanofi-Winthrop, Amgen, AbbVie. E. Giroux-Leprieur: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers-Squibb, Boehringer-Ingelheim, MSD, Novartis, Janssen, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: Takeda; Non-Financial Interests, Member of Board of Directors: French Intergroup of Thoracic Oncology IFCT. J. Raimbourg: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Pierre Fabre, Amgen, sanofi; Financial Interests, Institutional, Advisory Board: Takeda, BMS, Merck. M. Duruisseaux: Financial Interests, Personal, Advisory Board: BMS, GSK, Sanofi, MSD, AstraZeneca, AbbVie, Takeda, Boehringer Ingelheim, Merus, Amgen, Guardant, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, BMS, AstraZeneca, MSD, AbbVie, Takeda, Boehringer Ingelheim, Gamamabs Pharma, Pfizer; Financial Interests, Personal, Research Grant: Takeda, NanoString, Lilly, Blueprint. All other authors have declared no conflicts of interest.