1327P - First-line osimertinib in patients with EGFR mutated lung cancer with uncommon mutations (OCELOT study – interim analysis)

Background

The results of the FLAURA study established osimertinib as the new first-line (1L) standard of care for patients with the two ‘common’ types of epidermal growth factor receptor mutation-positive (EGFR+) advanced non-small-cell lung cancer (aNSCLC). Uncommon EGFR mutations (non-exon 19 del and L858R) occur in up to 20% of patients; however, the efficacy of osimertinib in this population is not well understood. To date, small prospective studies, retrospective case series, and case reports have signaled that osimertinib has a role in the treatment of patients with uncommon EGFR mutations.

Methods

This is a multicentered Canadian phase II investigator-initiated study of (cohort A) osimertinib in the third-line (3L) rechallenge of patients with EGFR+ aNSCLC, following 1L treatment with osimertinib and 2L therapy with platinum pemetrexed chemotherapy; and (cohort B) 1L osimertinib in patients with uncommon EGFR mutations (exon 20 insertions are not permitted). Cohort B has a planned accrual of 85 patients. The primary endpoint is objective response rate (ORR) in 3L osimertinib rechallenge; 1L ORR in patients with uncommon mutations is a key secondary endpoint. The OCELOT study, NCT04335292, is continuing to enroll participants.

Results

74 patients have been accrued to date, including 35 in Cohort B. At the time of preparation, 22 had evaluable disease. The most frequent ‘uncommon’ EGFR mutation was G719X (n=11), followed by L861X (n=8) and S768I (n=5). The confirmed ORR was 45% and disease control rate (DCR) was 77%. Confirmed ORR/DCR for evaluable patients with G719X (n=11), L861X (n=3) and S768I (n=5) mutations were 45%/73%, 100%/100%, and 60%/100%, respectively. Updated data including ORR, progression free survival, time to treatment failure and 1-year over survival rate will be presented. Safety and toxicity profile is consistent with published data on osimertinib.

Conclusions

Osimertinib appears to be highly active and well tolerated in patients with the more frequent ‘uncommon’ EGFR mutations (G719X, L861X, and S768I). The OCELOT study will be the largest study to date of 1L osimertinib in patients with EGFR+ aNSCLC harboring uncommon mutations.

Clinical trial identification

NCT04335292.

Editorial acknowledgement

Legal entity responsible for the study

Dr. Mark Vincent.

Funding

AstraZeneca.

Disclosure

D.A. Breadner: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Merck, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Board: Takeda. Y. Wang: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Merck, Takeda; Financial Interests, Institutional, Research Grant: AZ. M. Vincent: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck. All other authors have declared no conflicts of interest.