According to results from the phase 2 NeoCOAST-2, durvalumab plus single-arm platinum chemotherapy plus datopotamab deruxtecan showed the highest pathological complete response (pCR) rate among patients with early-stage, resectable non-small cell lung cancer (NSCLC), when compared to a series of other regimens including durvalumab, chemotherapy, and novel agents.

These results were first presented by Tina Cascone, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, at the 2024 World Conference on Lung Cancer.

In this open-label, multicenter, multi-arm platform study, 202 patients with untreated, resectable, stage IIA to IIIB NSCLC were stratified by PD-L1 expression (either <1% or ≥1%). Patients were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy plus the anti-CD73 monoclonal antibody oleclumab (Arm 1, n = 76); durvalumab plus platinum-doublet chemotherapy plus the anti-NKG2A monoclonal antibody monalizumab (Arm 2, n = 72); or durvalumab plus single-agent platinum chemotherapy plus the Trop-2–directed antibody-drug conjugate datopotamab deruxtecan (Arm 4, n = 54). Neoadjuvant therapy was administered once every 3 weeks for 4 cycles prior to surgery, followed by adjuvant treatment with durvalumab alone (Arm 4), plus olectinib in Arm 1, or plus monalizumab (Arm 2) until disease progression or for up to 1 year. The primary end points were pCR rate, safety, and toleratbility. Key secondary end points included investigator-assessed event-free survival (EFS), feasibility of surgery, major pathological response rate (mPR), and objective response rate (ORR).

Of patients who underwent or were ineligible for surgery, 92.2% of patients underwent surgery in Arm 1, 92.1% in Arm 2, and 95.8% in Arm 4. In the modified intention-to-treat population, the pCR rate was 20% in Arm 1, 26.7% in Arm 2, and 34.1% in Arm 4. The mPR rates were 45%, 53.3%, and 65.9%, respectively. The rates of pCR and mPR were generally numerically higher in Arm 4, regardless of PD-L1 expression. Dr Cascone et al noted, “Treatments in all arms lef to improvements in mPR rates along with mangeable safety profile and surgical rates comparable to currently approved neoadjuvant and perioperative immunotherapy-based regimens.” Grade ≥3 treatment-related adverse events occurred in 33.8% of patients in Arm 1, 38.0% in Arm 2, and 18.5% in Arm 4.

Dr Cascone et al, concluded, “This is the first global [phase 2] platform study showing encouraging efficacy and a manageable safety profile of an [antibody-drug conjugate] in the neoadjuvant NSCLC setting.”

Source:

Cascone T, Florian G, Bonanno L, et al. Neocoast-2: Efficacy and safety of neoadjuvant durvalumab (D) + novel anticancer agents + CT and adjuvant D ± novel agents in resectable NSCLC. Presented at the 2024 World Conference on Lung Cancer. September 7-10, 2024; San Diego, CA. Abstract #PL02.07