P03.03 MERMAID-1: A Phase III Study of Adjuvant Durvalumab plus Chemotherapy in Resected NSCLC Patients with MRD+ Post-Surgery

Abstract

chemotherapy in this setting have shown no benefit for stage IA tumors, and the current standard of care is observation alone. Checkpoint blockade with PD-1/PD-L1 inhibitors has shown considerable activity in NSCLC including in metastatic disease, as consolidation in stage III disease after chemoradiation, and in studies evaluating neoadjuvant immunotherapy. Given this activity and their favorable safety profile, we designed a study of adjuvant PD-1 inhibition following resection in stage I NSCLC. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial will enroll 368 patients randomized 1:1 to either Pembrolizumab 200mg IV every 3 weeks for up to 17 cycles or observation alone with scheduled CT scans and routine clinical follow-up. Stratification factors include PD-L1 TPS 50% vs. <50% and tumor size of 1-2cm vs. >2-4cm. The sample size is based on the hypothesis that adjuvant Pembrolizumab will increase 3-year disease free survival (DFS) from 75% to 84.15% (HR¼0.6) with a power of 80% and a type I error of 0.1. The lead site is Indiana University, and the trial will be conducted through the Big Ten Cancer Research Consortium. The primary endpoint is DFS, and secondary endpoints include OS, DFS at 1-, 2-, and 3-year time points, and toxicity. The trial opened to accrual at the lead site in May 2020, and there are currently 2 patients enrolled.

Neoadjuvant and Adjuvant Immunotherapy in Early-Stage Non-Small-Cell Lung Cancer, Past, Present, and Future

“…Most ongoing trials assess only PD-L1 but no other potential biomarkers. MERMAID-1 and -2 are studies of note because they assess the benefits of adjuvant durvalumab in patients with MRD + status, which is determined by circulating tumor DNA [ 39 , 40 ]. The identification of optimal biomarkers is of utmost importance, as giving immunotherapy to non-responding patients may delay curative resection and increase the risk of progressive disease.…”

“…MERMAID-1 is a phase III, multicenter, double-blind study that will recruit approximately 332 minimal residual disease (MRD) positive patients with completely resected stage II–III NSCLC [ 39 ]. Participants are randomized to receive adjuvant durvalumab plus standard of care chemotherapy versus placebo plus standard of care immunotherapy.…”

Adjuvant immunotherapy of operable non-small cell lung cancer: achievements and treatment prospects

“…В условиях адъювантной терапии, т. е. после полной резекции опухоли, этот режим может обеспечить дополнительное преимущество безрецидивной выживаемости по сравнению с одной только химиотерапией. Оценка MRD может способствовать более ранней, более селективной адъювантной терапии для пациентов с MRD+, позволяя интенсифицировать лечение этого потенциально биологически отличного заболевания, сводя к минимуму чрезмерное лечение пациентов с MRD- [38].…”

Management of Resectable Stage III-N2 Non-Small-Cell Lung Cancer (NSCLC) in the Age of Immunotherapy

“…Some ongoing studies are trying to elucidate whether MRD assessment has utility in adjuvant setting. The MERMAID-1 phase III trial (NCT04385368) is evaluating DFS in MRD-positive patients with resected stage II-III NSCLC treated with adjuvant durvalumab plus chemotherapy followed by durvalumab or placebo plus chemotherapy followed by placebo for up to 12 months [ 65 ]. On the other hand, the MERMAID-2 phase III trial (NCT04642469) is evaluating the efficacy of durvalumab vs. placebo in patients with MRD-positive resected stage II-III NSCLC, while those patients without MRD will only undergo surveillance.…”