Margaret K. Callahan, MD, PhD
Formal discussant of the mRNA-4157-P201/KEYNOTE-942 trial, Margaret K. Callahan, MD, PhD, Research Director, Immunotherapeutics Program, Memorial Sloan Kettering Cancer Center, New York, agreed that finding an effective cancer vaccine has been challenging, and she is “cautiously optimistic” about the new mRNA vaccine.
“Despite hundreds of trials, cancer vaccines have been disappointing so far. In some cases, phase II studies have looked promising but then ‘roller coastered’ down in phase III. Is this study a game-changer?” she asked.
Dr. Callahan continued: “Shared tumor antigens are inferior to unique tumor-specific antigens, but even if you generate antitumor response, there may be additional barriers for immune responses. We have learned that immune responses don’t always lead to clinical efficacy, and we need to exhibit caution,” she told listeners.
“It is an achievement that personalized neoantigen vaccines are now possible. The authors are to be congratulated for presenting the first randomized study of a vaccine with a clinical endpoint. The 16% improvement in recurrence-free survival at 18 months is clinically meaningful for a high-risk population,” she said.
“Some reasons for caution are that we set a low bar for statistical rigor, and there are imbalances in PD-L1/tumor mutational burden between cohorts. We have a history of challenges with cancer vaccine studies, and we don’t know which antigens are clinically relevant. Also, as new data emerge, adjuvant PD-1 monotherapy may no longer be the standard, and neoadjuvant therapy may rapidly become the standard of care,” Dr. Callahan commented.
“These promising results merit further study in a randomized phase III study that incorporates what we have learned. We need to determine whether it is feasible to incorporate a vaccine into neoadjuvant therapy and which neoantigens are clinically relevant. Also, we need to determine whether there any immune correlates that are clinically relevant,” Dr. Callahan concluded.
DISCLOSURE: Dr. Callahan reported financial relationships with Bristol Myers Squibb, Immunocore, AstraZeneca, and Atreca Therapeutics.
