By Peter J. O’Dwyer, MD (left)
and Mitchell D. Schnall, MD, PhD

A great deal is happening fast in our cancer research world, much of it since our last newsletter. At that time, we had just drawn the line under the NCI-MATCH trial, which closed in January. Now, we celebrate the opening of ComboMATCH, the next generation of precision medicine trials for adults with solid tumors. There are several differences between MATCH and ComboMATCH, the main one residing in the name.  Most of the arms of NCI-MATCH were single agents, and with a few exceptions, yielded unremarkable response rates in the heavily pretreated population in that trial. It is also clear from correlative analyses in MATCH, and the long-recognized complex genomic landscapes of solid tumors, that targeting single driver mutations in tumors that may harbor several may have limited impact on tumor growth.

In ComboMATCH, the combinations are directed to a less heavily pretreated population, and moreover have more rigorous criteria for inclusion than were used for MATCH. Just as in the latter part of the MATCH trial, the identification of candidate mutations at either academic or commercial labs will generate a notification that a patient may be eligible for a substudy. Please be on the lookout for such messages. Within each substudy, there is usually more than one cohort and often a randomization in a tumor-specific design. The ECOG-ACRIN registration trial is the gateway to ComboMATCH, and eligible patients are then referred to self-contained substudies that reside in all four Cooperative Groups.

Also announced in recent weeks is a new clinical trial mechanism, the Clinical Trials Innovation Unit, which is a cross-agency interaction initiated by Drs. Bertagnolli and Pazdur, with clinical studies to be performed under the aegis of the Groups. This exciting new endeavor has the potential to bring cutting-edge novel studies, some that might face obstacles in our current review systems, and to have them completed quickly. The twin goals of novelty and impact will guide selection, and a portal will soon be available for submissions. Committee leaders are aware of the opportunity, and some discussion of proposals would be appropriate at the Spring Group Meeting in Chicago. An attractive feature of the new structure is that it will be financed by new clinical research money, and so does not draw resources away from CTEP-funded activities.

Finally, also unveiled in recent weeks is a revision of the National Cancer Plan, which is a responsibility of Dr. Bertagnolli in addition to her role as director of the NCI. The plan is an up-to-date and detailed analysis of the domains in which we will have to be active and aware in order to halve the death rate from cancer in the next 25 years, as announced by President Biden in his State of the Union address. Each one of these is an area in which we have current research. View the eight priority areas on the National Cancer Plan website. Dr. Bertagnolli has emphasized that this should be a living document, and no doubt emphasis may change with time, but these elements are appropriate to our time. Perhaps most important, you can see that everyone has a stake in this, and everyone has a contribution to make. What will be yours? Let us know, talk about it, persuade others, and translate into action.

We’ll have a lot to talk about in Chicago in May!

Read the April 2023 issue here.