MSK Expertise on Precision Medicine Highlighted in American Association for Cancer Research Annual Meeting Press Program

David Hyman, MD, speaks to a patient

David Hyman, MD, speaks to a patient.

Research findings from Memorial Sloan Kettering Cancer Center (MSK) will be featured in this year’s American Association for Cancer Research (AACR) Annual Meeting press program. The AACR is the oldest and largest professional organization dedicated to advancing cancer research, and the press program highlights cancer research that a panel of AACR experts considers the most significant of the year and deserving of media attention. Details of the presentation are as follows:

Who: David Hyman, MD, Director of Developmental Therapeutics, Memorial Sloan Kettering Cancer Center

What: Findings from the phase II SUMMIT trial, a “second-generation basket trial” testing the investigational pan-HER-targeted therapeutic neratinib in patients with HER2 and HER3 mutations in a variety of cancer types.

When: Press conference scheduled for April 2,

Presentation will follow the press conference as part of the Clinical Trials Plenary Session, beginning at 12:45 .

Dr. Hyman will share findings of the phase II SUMMIT clinical trial, testing the investigational pan-HER-targeted therapeutic neratinib in patients with HER2 and HER3 mutations in a wide variety of cancer types. This trial provides the largest body of clinical data to date on the use of a pan-HER inhibitor in patients with solid tumors with somatic HER2/HER3 mutations. Researchers found that the likelihood that a patient’s cancer responded was influenced by both the cancer type and the identity of the gene mutation present in the cancer.

Dr. Hyman and colleagues at MSK pioneered the concept of the basket trial, a type of research study that concentrates on a specific mutation found in the tumor. The team published the findings from the first basket trial in the New England Journal of Medicine in 2015. The phase II SUMMIT trial builds on previous basket trials by examining, for the first time, how both different mutations within a gene as well as various cancer types each influence likelihood of response to genomically targeted therapy. Setting itself apart from the first generation of basket trials, this new trial design looks at a genomic target that is not yet credentialed, while previous trials set out to broaden the use of approved treatments for a specific mutation across a number of cancer types.

“What we’re doing here is accelerating the process of testing drugs in people,” explained Dr. Hyman. “As the field of precision medicine has progressed, clinical trial designs have evolved greatly. This work shows that second-generation basket trials will serve as a valuable trial design since we now know that we must assess both cancer type and specific mutation when identifying targeted therapies. This study also demonstrates the importance of enrolling a sufficient number of patients in molecularly driven studies for which we expect significant heterogeneity of response by tumor type and mutation. If we do not ensure sufficient study size, we could easily miss potential benefit in specific tumor types of mutations and therefore the opportunity to advance the standard of care for affected patients.”

At interim data cutoff, which was December 16, 2016, 141 HER2 and HER3 patients had received neratinib as part of the clinical trial. Among these were patients with 21 unique types of cancer, 30 unique HER2 gene mutations, and 12 HER3 gene mutations. The most common types of cancer were bladder, breast, colorectal, and non–small cell lung cancer; the most common HER2 gene mutations included S310, L755, A755_G776insYVMA, and V777. When looking at the data by cancer type, the best response rate was seen for breast cancer; biliary and cervical showed an intermediate response rate; there were no responses seen for colorectal cancer. The researchers noted that while there are areas of promise in these findings, combination therapies with pan-HER inhibitors and other treatment modalities will likely need to be explored in order to obtain practice-changing response rates and durability of response.