The KRAS Story in Lung Cancer: Dosing Lessons to Learn From the Accelerated Approval of Sotorasib With Harpreet Singh, MD, and Matthew Hadfield, DO
Expert Perspectives · Keira Smith · 2024-10-30
In this interview, Matthew Hadfield, DO, sat down with Harpreet Singh, MD, the Chief Medical Officer at Precision for Medicine and former Division Director of Oncology at the FDA, to discuss an article that recently came out regarding the dosing conundrum following the accelerated approval of sotorasib for KRAS-mutated advanced lung cancer in May 2021.
Accelerated Approval of Sotorasib: The Dosing Conundrum and Lessons Learned
The approval was accompanied by a post-marketing requirement for conducting a randomized clinical trial to determine the optimal dosage. The trial, which compared the approved 960 mg once-daily dosage against a lower 240 mg once-daily dose, addressed important questions about safety and efficacy in the context of ongoing clinical trial development.
The publication of the results, on which Dr. Singh is an author, yielded key insights into dosing lessons to be learned from sotorasib’s accelerated approval, including:
- The impact that the development of more novel and targeted therapies will have on clinical trial design
- How regulatory approval bodies are adapting to newer therapies
- What changes the coming years will see in how trials are conducted to accommodate the rapid pace of clinical development
- Bringing the patient voice into decisions about therapeutic dosing and potential toxicities
- And more!
How Sotorasib Is Informing Ongoing Trial Development
“It all goes back to trial design. Let’s make sure that our trial designs keep the patients at the center. How do you do that? You do things like offering crossover within the trial design. That means that if you are randomized to the control arm, if you progress on the therapy, you immediately will be crossed over or get access to the drug on the experimental arm. From a regulatory standpoint, around the world, we can reevaluate how much data is needed to make regulatory decisions and on what end points. Could any work be done around assuring ourselves and assuring regulatory bodies that early promising results will in fact result in benefit on the time to the end point?” – Harpreet Singh, MD
About Dr. Hadfield and Dr. Singh
Matthew Hadfield, DO, is a Medical Oncologist at Brown University/Legorreta Cancer Center, with a pending faculty appointment at the Warren Alpert School of Medicine of Brown University. He recently completed his Hematology/Oncology Fellowship at Brown University. Dr. Hadfield’s clinical and research interests are in phase 1 clinical trials and developmental therapeutics, as well as cutaneous malignancies and immunotherapy-related adverse events.
Harpreet Singh, MD, is the Chief Medical Officer at Precision for Medicine and a former Division Director of Oncology at the FDA, where she oversaw the development of multiple KRAS drugs. Her extensive background also includes her role as Associate Director for Cancer in Older Adults and Special Populations at the FDA Oncology Center of Excellence, as well as a fellowship at the National Cancer Institute. Dr. Singh is recognized for her innovative contributions to drug development.