Imfinzi and tremelimumab with chemotherapy demonstrated sustained survival benefit in metastatic non-small cell lung cancer, nearly doubling the number of patients alive after three years vs. chemotherapy

Exploratory analysis from POSEIDON Phase III trial also showed trends for overall survival benefit with a limited course of tremelimumab added to Imfinzi and chemotherapy in subgroups with high unmet need

Updated results after approximately four years of follow-up of the POSEIDON Phase III trial showed a limited course of tremelimumab when added to AstraZeneca’s Imfinzi (durvalumab) plus four cycles of chemotherapy demonstrated a sustained improvement in overall survival (OS) compared to chemotherapy alone in the 1st-line treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC). Additional post-hoc, exploratory analyses continued to show a trend for OS improvement with this combination in patients with STK11, KEAP1 and KRAS-mutated NSCLC, as well as in patients whose tumours were PD-L1-negative (less than 1% tumour cell expression).

These late-breaking results were presented today at the European Society of Medical Oncology (ESMO) Congress 2022 (Abstract #LBA59).

KRAS mutations are the most common tumour growth driver in NSCLC, occurring in approximately 25% of patients. NSCLC tumours with STK11 and KEAP1 mutations are often associated with poor outcomes and classified as immunologically “cold.” KRAS-mutated NSCLC can be responsive to immunotherapy but also can have poor outcomes, particularly when associated with STK11 or KEAP1 co-mutations.1-6

Melissa Johnson, MD, Director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology in Nashville, Tennessee, and a lead investigator in the POSEIDON Phase III trial, said: “Metastatic non-small cell lung cancer is a devastating diagnosis, particularly for patients whose cancers are less responsive to standard treatments such as chemotherapy and immune therapy. These results support the addition of a limited course of tremelimumab to durvalumab plus chemotherapy as a potential new treatment option for patients with these harder-to-treat forms of lung cancer.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These updated POSEIDON results at nearly four years of follow-up show further evidence that the addition of a limited course of tremelimumab to Imfinzi plus chemotherapy improves outcomes for metastatic non-small cell lung cancer patients, including those with specific tumour mutations where a high unmet need for effective, well tolerated treatments remains. We look forward to bringing this potential new treatment option to patients as quickly as possible.”

These latest data show that a limited course of five cycles of tremelimumab added to Imfinzi plus platinum-based chemotherapy improved overall survival by 25% compared to chemotherapy alone (hazard ratio [HR] 0.75; 95% CI 0.63-0.88). Updated median OS was 14 months for the combination versus 11.7 for chemotherapy alone. An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone.

A trend for OS improvement continued to be observed in patients with STK11KEAP1, and KRAS-mutated mNSCLC when treated with the combination, which reduced the risk of death by 38% (based on a HR of 0.62; 95% CI 0.34-1.12), 57% (based on a HR of 0.43; 95% CI 0.16-1.25), and 45% (based on a HR of 0.55; 95% CI 0.36-0.85), respectively. The combination also extended sustained OS benefit to patients with less than 1% PD-L1 tumour cell expression. These post hoc, exploratory subgroup analyses should be interpreted with caution due to the small sample sizes.

Consistent with previous POSEIDON Phase III trial readouts, OS benefit in these updated results appeared more pronounced with tremelimumab plus Imfinzi and chemotherapy in patients with non-squamous NSCLC histology. A 32% improvement in OS compared to chemotherapy alone (HR 0.68; 95% CI 0.55–0.85) was reported for patients with non-squamous histology, with an updated median OS of 17.2 months for the combination versus 13.1 months for chemotherapy. An estimated 31.4% of patients with non-squamous NSCLC treated with the combination were alive at three years versus 17.3% for those receiving chemotherapy alone.

Summary of efficacy resultsi, ii

  Tremelimumab + Imfinzi + chemotherapy Chemotherapy
Intention-To-Treat (ITT) n=338 n=337
Median OS (in months) 14.0 11.7
Hazard ratio (95% CI)iii 0.75 (0.63, 0.88)
OS rate at 3 years (%) 25.0 13.6
STK11 mutation n=31 n=22
Median OS (in months) 15.0 10.7
Hazard ratio (95% CI)iv 0.62 (0.34, 1.12)
OS rate at 3 years (%) 25.8 4.5
KEAP1 mutation n=22 n=6
Median OS (in months) 13.7 8.7
Hazard ratio (95% CI)iv 0.43 (0.16, 1.25)
OS rate at 3 years (%) 30.0 0.0
KRAS mutation n=60 n=53
Median OS (in months) 25.7 10.4
Hazard ratio (95% CI)iv 0.55 (0.36, 0.85)
OS rate at 3 years (%) 40.0 15.8

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