This newsletter is themed on endpoint surrogacy in oncology drug development. In April, the ODAC voted unanimously 12:0 in favor of MRD as an endpoint suitable for accelerated approval in multiple myeloma. This newsletter includes a thoughtful reflection on the meeting, contributed by Gu. This ODAC meeting sparked hot discussions in the community about what comes next. In addition to regulatory considerations supporting accelerated approval, a critical topic for sponsors in oncology drug development is determining the optimal strategies for making Go/No-Go decisions ensuring that resources are allocated effectively. As Mullard wrote in Nature Reviews Drug Discovery in 2023 “… around $60 billion per year is spent on unsuccessful cancer drugs … More work is needed on the predictive validity of R&D tools”. Over the past decades, several intermediate and surrogate endpoints have been identified to evaluate the effectiveness of cancer drugs, including objective response rate (ORR), pathologic complete response (pCR), minimal residual disease (MRD), circulating tumor DNA (ctDNA), progression-free survival (PFS), and tumor growth (g). A significant body of research has been devoted to understanding the relationship between these endpoints and long-term survival benefits, aiming to establish their validity as predictors of overall outcomes. However, given the complexity of various disease settings, continued research efforts remain essential to further elucidate these relationships and optimize their use in drug development and clinical practice.

Gormley (2024) classified the oncology endpoints into 4 categories: clinical benefit endpoints, surrogate endpoints that predict clinical benefit, surrogate endpoints that are reasonably likely to predict clinical benefit, and intermediate endpoints. Ananthakrishnan et al. provides more detailed information in the Biostat Bytes section. Chen et al. compiles the existing data to understand the role of pCR across various solid tumors. We hope you enjoy reading the KOL message by Devlin who was greatly involved in the research of the MRD endpoint.

Detailed description of the content includes:

· Intermediate/Surrogate Endpoints Balancing Speed and Scientific Rigor. By co-chairs Philip He and Laura Fernandes

· KOL Message: My Journey with the MRD ODAC. By Sean Devlin

· Reflections on the ODAC Meeting about MRD as an Endpoint to Support Accelerated Approval. By Gu Mi

· The Use of Circulating Tumor DNA (ctDNA) in Early-stage Solid Tumor Drug Development. By Haijun Ma and Jonathan Fawcett.

· A Summary of the Association Between Pathologic Complete Response (pCR) and Long-term Survival across Multiple Cancer Types. By Natalie Ren, Jean Fan, Sohail Chaudhry and Philip He

· FDA Oncologic Drugs Advisory Committee (ODAC) and FDA Oncology Approvals in Q2, 2024. By Fengyu Zhao

· Upcoming Conferences and Workshops

· Biostat Bytes: Surrogate and Intermediate Endpoints. By Revathi Ananthakrishnan, Haijun Ma, and Philip He.

You can access and download the newsletter at https://www.doi.org/10.5281/zenodo.13770527.