PD-1 matchmaking

Courting combinations with PD-1

The rush to find combinations of PD-1 inhibitors and established cancer therapies marks the end of the beginning, rather than the beginning of the end, of the search for ways to extend use of checkpoint inhibitors to the two-thirds of patients who are non-responders. The new thinking is that emerging targets in the tumor microenvironment can either turbo-boost PD-1 or re-arm the immune response, but researchers will need a streamlined strategy to select the right targets to match in different tumors.

The concept of targeting the tumor microenvironment is moving fast from the lab to the boardroom. Two weeks ago, Surface Oncology Inc. announced a $35 million series A round led by the company's seed investor, Atlas Venture. The newco was set up late last year to find immune processes beyond PD-1 that can be targeted in cancer.

In addition, several companies and institutions that have been focusing on individual checkpoint targets - dubbed co-inhibitors - are starting to test their compounds in combination with PD-1 (See <div>Table: Co-inhibitory and co-stimulatory targets</div>).With clinical response rates to PD-1/PD-L1-targeted compounds in the 30-40% range, many pharmas have taken the obvious step of looking on their shelves to see what other cancer therapies could combine additively - or if lucky, synergistically - to improve outcomes.

The most advanced checkpoint inhibitor to be combined with PD-1 therapies is the CTLA-4 mAb Yervoy ipilimumab, marketed by Bristol-Myers Squibb Co. and Ono Pharmaceutical Co. Ltd. for melanoma. The drug is also in Phase I to Phase III trials

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