Late-breaking post-hoc exploratory results from the POSEIDON Phase III trial suggest a trend for improved overall survival (OS) with a limited course of five cycles of tremelimumab added to AstraZeneca's IMFINZI (durvalumab) plus platinum chemotherapy, in the 1st-line treatment of patients with STK11, KEAP1 or KRAS-mutated Stage IV (metastatic) non-small cell lung cancer (mNSCLC).

These results will be presented on 9 August 2022 at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC) (Abstract #OA15.04).

NSCLC tumors with STK11 and KEAP1 mutations are often associated with a poor prognosis and frequently classified as immunologically 'cold', with immune T-cells missing from the tumor.1,2 KRAS-mutated NSCLC is typically responsive to immunotherapy, unless associated with STK11 or KEAP1 co-mutations where outcomes are often poor.1,2 KRAS mutations are the most common tumor growth driver in NSCLC representing approximately 25% of patients; while an estimated 6-15% of NSCLC is KEAP1-mutated and approximately 15% of NSCLC is KRAS-driven and STK11-mutated.1,3-6

A trend for OS improvement was observed in the POSEIDON Phase III trial for patients with these mutations when treated with a limited course of tremelimumab added to IMFINZI (durvalumab) plus platinum chemotherapy compared to chemotherapy. The exploratory analysis reported a hazard ratio (HR) of 0.56 (95% CI 0.30-1.03) for STK11-mutated non-squamous NSCLC, an HR of 0.43 (95% CI 0.16-1.25) for KEAP1-mutated NSCLC, and 0.56 (95% CI 0.36-0.88) for KRAS-mutated non-squamous NSCLC.

Median OS and two-year survival rates across all mutational subgroups also increased with the immunotherapy combination compared to chemotherapy. The STK11 and KRAS subgroup analyses were presented for patients with non-squamous histology; while the KEAP1 subgroup analysis was presented for all mutation-evaluable patients irrespective of tumor histology, due to a small sample size. These subgroup analyses should be interpreted with caution as they are post hoc, exploratory and of smaller sample sizes.

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: 'These exploratory analyses for POSEIDON presented at WCLC are an encouraging sign for a group of metastatic lung cancer patients whose prognosis is particularly poor. We are eager to continue following the science to fully understand how patients with these specific mutations and with PD-L1 negative lung cancer respond to immunotherapy combinations including CTLA-4 inhibitors. These initial survival associations warrant further study.'

Also at WCLC, additional exploratory analyses from the POSEIDON Phase III trial evaluated outcomes in patient subgroups whose tumors were PD-L1-negative (tumor cell [TC] expression

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