Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study.

التفاصيل البيبلوغرافية
العنوان:	Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study.
المؤلفون:	Weber, Jeffrey S¹ (AUTHOR) Jeffrey.Weber@nyulangone.org, Carlino, Matteo S² (AUTHOR), Khattak, Adnan^3,4 (AUTHOR), Meniawy, Tarek⁵ (AUTHOR), Ansstas, George⁶ (AUTHOR), Taylor, Matthew H⁷ (AUTHOR), Kim, Kevin B⁸ (AUTHOR), McKean, Meredith⁹ (AUTHOR), Long, Georgina V^10,11 (AUTHOR), Sullivan, Ryan J¹² (AUTHOR), Faries, Mark¹³ (AUTHOR), Tran, Thuy T¹⁴ (AUTHOR), Cowey, C Lance¹⁵ (AUTHOR), Pecora, Andrew¹⁶ (AUTHOR), Shaheen, Montaser¹⁷ (AUTHOR), Segar, Jennifer¹⁸ (AUTHOR), Medina, Theresa¹⁹ (AUTHOR), Atkinson, Victoria²⁰ (AUTHOR), Gibney, Geoffrey T²¹ (AUTHOR), Luke, Jason J²² (AUTHOR)
المصدر:	Lancet. Feb2024, Vol. 403 Issue 10427, p632-644. 13p.
مصطلحات موضوعية:	PEMBROLIZUMAB, ADVERSE health care events, MELANOMA, MESSENGER RNA
الشركة/الكيان:	MERCK KGaA
مستخلص:	Checkpoint inhibitors are standard adjuvant treatment for stage IIB–IV resected melanoma, but many patients recur. Our study aimed to evaluate whether mRNA-4157 (V940), a novel mRNA-based individualised neoantigen therapy, combined with pembrolizumab, improved recurrence-free survival and distant metastasis-free survival versus pembrolizumab monotherapy in resected high-risk melanoma. We did an open-label, randomised, phase 2b, adjuvant study of mRNA-4157 plus pembrolizumab versus pembrolizumab monotherapy in patients, enrolled from sites in the USA and Australia, with completely resected high-risk cutaneous melanoma. Patients with completely resected melanoma (stage IIIB–IV) were assigned 2:1 to receive open-label mRNA-4157 plus pembrolizumab or pembrolizumab monotherapy. mRNA-4157 was administered intramuscularly (maximum nine doses) and pembrolizumab intravenously (maximum 18 doses) in 3-week cycles. The primary endpoint was recurrence-free survival in the intention-to-treat population. This ongoing trial is registered at ClinicalTrials.gov , NCT03897881. From July 18, 2019, to Sept 30, 2021, 157 patients were assigned to mRNA-4157 plus pembrolizumab combination therapy (n=107) or pembrolizumab monotherapy (n=50); median follow-up was 23 months and 24 months, respectively. Recurrence-free survival was longer with combination versus monotherapy (hazard ratio [HR] for recurrence or death, 0·561 [95% CI 0·309–1·017]; two-sided p=0·053), with lower recurrence or death event rate (24 [22%] of 107 vs 20 [40%] of 50); 18-month recurrence-free survival was 79% (95% CI 69·0–85·6) versus 62% (46·9–74·3). Most treatment-related adverse events were grade 1–2. Grade ≥3 treatment-related adverse events occurred in 25% of patients in the combination group and 18% of patients in the monotherapy group, with no mRNA-4157-related grade 4–5 events. Immune-mediated adverse event frequency was similar for the combination (37 [36%]) and monotherapy (18 [36%]) groups. Adjuvant mRNA-4157 plus pembrolizumab prolonged recurrence-free survival versus pembrolizumab monotherapy in patients with resected high-risk melanoma and showed a manageable safety profile. These results provide evidence that an mRNA-based individualised neoantigen therapy might be beneficial in the adjuvant setting. Moderna in collaboration with Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA. [ABSTRACT FROM AUTHOR]
قاعدة البيانات:	Academic Search Index

الوصف
تدمد:	01406736
DOI:	10.1016/S0140-6736(23)02268-7