Interim data from the NeoCOAST-2 Phase 2 trial, presented at the 2024 World Conference on Lung Cancer, indicate that the addition of monalizumab to durvalumab and platinum-based chemotherapy shows promising results in patients with resectable, early-stage non-small cell lung cancer (NSCLC). The study, sponsored by AstraZeneca and Innate Pharma, suggests a potential improvement in pathological response rates with the novel combination.
The NeoCOAST-2 platform study (NCT05061550) is designed to evaluate the safety and efficacy of neoadjuvant durvalumab, alone or in combination with novel agents and chemotherapy, followed by adjuvant treatment with durvalumab with or without the novel agents. The presented data focused on three arms:
- Oleclumab with durvalumab and platinum doublet chemotherapy (neoadjuvant) followed by durvalumab plus oleclumab (adjuvant).
- Monalizumab with durvalumab and platinum doublet chemotherapy (neoadjuvant) followed by durvalumab plus monalizumab (adjuvant).
- Datopotamab deruxtecan with durvalumab and single-agent platinum chemotherapy (neoadjuvant) followed by durvalumab alone (adjuvant).
Monalizumab Arm Results
Preliminary analysis of the first 60 of 72 patients randomized to the monalizumab arm revealed a pathological complete response (pCR) rate of 26.7% (95% CI: 16.1-39.7) and a major pathological response (MPR) rate of 53.3% (95% CI: 40.0-66.3). These rates are numerically higher than those observed with the durvalumab plus platinum doublet regimen alone, which is an approved treatment. The addition of monalizumab did not negatively impact the surgical rate, and the treatment regimen demonstrated a manageable safety profile.
Mechanism of Action and Clinical Significance
Monalizumab is a first-in-class immune checkpoint inhibitor targeting the NKG2A receptor, which is expressed on tumor-infiltrating cytotoxic CD8+ T cells and NK cells. NKG2A serves as an inhibitory checkpoint for HLA-E, a molecule frequently overexpressed in cancer cells, allowing them to evade immune detection. By blocking NKG2A, monalizumab aims to restore and broaden anti-tumor immune responses mediated by NK and T cells, potentially enhancing the effectiveness of other therapeutic antibodies.
Dr. Sonia Quaratino, Chief Medical Officer of Innate Pharma, stated, "We’re pleased to see the preliminary results from the NeoCOAST-2 Phase 2 trial presented at WCLC and the encouraging clinical outcomes for patients with early-stage non-small cell lung cancer across all treatment arms. Based on these preliminary results, we remain excited about the potential of extending the clinical benefit of durvalumab in the neoadjuvant/adjuvant setting with the addition of monalizumab in patients with non-small cell lung cancer. We look forward to the final analysis and the translation of these preliminary data to Event Free Survival (EFS) data in due course."
NSCLC Context
In 2022, approximately 2.5 million individuals were diagnosed with lung cancer globally. NSCLC accounts for 80-85% of all lung cancer cases, with Stage III NSCLC representing about one-quarter of NSCLC diagnoses. These locally advanced cases are further divided into IIIA, IIIB, and IIIC subcategories based on the extent of local cancer spread.
