1412P - SAKK 17/18-ORIGIN trial: Efficacy and safety from a multicenter phase II trial of gemcitabine and atezolizumab in patients with advanced NSCLC progressing on immune checkpoint inhibitors

Background

A significant number of patients (pts) with advanced non-small cell lung cancer (NSCLC) do not respond to therapy with immune checkpoint inhibitors (ICI). After relapse, treatment options are limited. We have previously demonstrated in a preclinical in vivo model that the combination of ICI and gemcitabine (GEM) can overcome resistance to ICI or GEM alone. ORIGIN (NCT04480372) is a multicenter phase II trial of GEM and atezolizumab (ATEZO) in patients with advanced non-small cell lung cancer (NSCLC) and mesothelioma (MPM) progressing on ICI. Here we report the data of the NSCLC cohort.

Methods

Eligible pts had ECOG PS 0-2, with confirmed NSCLC stage IIIB-IV with disease recurrence or progression during or after ≥ prior line of ICI or chemo-ICI and available tissue for translational research. Pts received GEM (1000mg /m2 IV d1, 8 q3w) and ATEZO (1200 mg IV q3w). The primary endpoint (EP) was overall response rate (ORR) of the full analysis set (FAS) evaluated by independent radiological assessment. 35 pts were needed based on a one-sided type I error of 10% and a power of 80% for H₁ ORR ≥25% compared to H₀ ORR ≤11%. Key secondary EPs were progression free survival (PFS), disease control rat (DCR) at 18 weeks, duration of response (DoR), overall survival (OS) and safety.

Results

Between 03/2021 and 10/2021 37 pts were accrued and received GEM+ATEZO after a median of 2 prior lines of treatment (range 1-8). 36 patients were included in the FAS. Pts with ECOG PS 0, 1 and 2 were 25%, 56% and 19% resp; females represented 44% of pts and median age was 67y (48-80). At data cutoff, median follow-up was 17.6 mo. ORR was 31% (one-sided 90%CI: 20%, 95%CI: 16%-48%) and 22% of pts had stable disease. Median PFS was 4.0 mo (95% CI: 2.5-5.3), DCR at 18 weeks was 42% (95%CI: 26%-59%); median DoR was 5.2 mo (95% CI: 1.1-not reached) and median OS 8.2 mo (95% CI: 6.1-10.1). Treatment-related AEs occurred in 89% (G3-4, 59%) and led to discontinuation in 19% of pts. Extensive translational research on longitudinal blood samples is ongoing.

Conclusions

ORIGIN met its primary endpoint with an ORR of 31% in heavily pre-treated NSCLC patients with no unexpected toxicity profile of GEM or ATEZO.

Clinical trial identification

NCT04480372.

Editorial acknowledgement

Legal entity responsible for the study

SAKK (Swiss Group for Clinical Cancer Research).

Funding

Roche supported SAKK.

Disclosure

A. Curioni-Fontecedro: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Meyer Squibb, Boehringer Ingelheim, MSD, Novartis, Amgen, Roche, Takeda, Janssen; Non-Financial Interests, Leadership Role: Swiss Academy for Clinical Cancer Research (SAKK); Non-Financial Interests, Principal Investigator, of clinical trials: Roche; Non-Financial Interests, Principal Investigator, Clinical Trials: Takeda, MSD, Bristol Meyer Squibb, Amgen. M. Frueh: Financial Interests, Personal, Research Grant: MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: MSD, Roche, BMS, Pfizer, Takeda. S. Weindler: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Research Funding: Merck, BMS; Financial Interests, Institutional, Other, Travel: Vifor, Eli Lilly. D. König: Financial Interests, Personal, Other, Consultant: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Amgen, Sanofi; Financial Interests, Personal, Other, Travel: Amgen, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, MSD. A. Addeo: Financial Interests, Institutional, Advisory Board: BMS, AZD, Roche, Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer, Takeda, MSD; Financial Interests, Institutional, Invited Speaker: Novartis. C. Britschgi: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer Ingelheim, Merck, Sanofi; Financial Interests, Personal, Other, Travel: AstraZeneca, Amgen, Takeda. A. Bettini: Financial Interests, Personal, Advisory Board: MSD, Merk, Janssen; Other, Travel fees: Roche, Amgen; Other, Inscription fees: AstraZeneca. M. Joerger: Financial Interests, Institutional, Coordinating PI, Clinical study activity: Basilea, Bayer, BMS, Immunophotonics, MSD, Novartis, Roche; Financial Interests, Institutional, Other, Clinical study activity: DaiichySankyo; Financial Interests, Institutional, Local PI, Clinical study activity: Innomedica; Non-Financial Interests, Advisory Role: Novartis, AstraZeneca, Basilea, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi. All other authors have declared no conflicts of interest.