GSK stops Keytruda combo trials after ICOS drug falls short

GlaxoSmithKline has stopped two clinical trials of feladilimab in combination with Keytruda after an interim review. Other studies of the ICOS agonist are continuing, but the future of the program is now in doubt.

Feladilimab, formerly known as GSK3359609, is designed to stimulate and grow cytotoxic T cells by acting on ICOS. The mechanism of action suggests ICOS agonists may enhance checkpoint inhibitors, leading GSK and Merck to start studying the combination of feladilimab and PD-1 drug Keytruda. The theory took a hit late last year when Jounce Therapeutics stopped a trial that was testing its rival ICOS candidate in combination with Bristol Myers Squibb’s CTLA-4 inhibitor Yervoy.

Now, GSK has dealt another blow to the cases for ICOS agonists. After seeing interim results from a trial in PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients, the independent data monitoring committee recommended stopping the INDUCE-3 study. 

Participants in the phase 2 trial received feladilimab or placebo on top of Keytruda as a first-line treatment. In February, Hal Barron, M.D., chief scientific officer at GSK, said encouraging interim data would “un-gate” the phase 3 part of the trial. Instead, GSK has stopped enrollment and dosing. 

The action extends to another phase 2/3 clinical trial of feladilimab, INDUCE-4. That clinical trial was testing feladilimab in combination with Keytruda, platinum-based chemotherapy and 5-fluorouracil as a first-line treatment in patients with recurrent metastatic HNSCC. Again, positive data would have unlocked the phase 3 portion of the study but the setback to INDUCE-3 persuaded GSK to pull the plug early.

GSK is now evaluating all its data to assess the impact on the overall feladilimab clinical development program. Investigators are evaluating feladilimab in two phase 2 platform studies. One study is giving feladilimab in combination with one of a handful of other drugs to patients with non-small cell lung cancer. The other study is evaluating a number of drugs, including feladilimab, in combination with anti-BCMA therapy Blenrep in multiple myeloma patients. 

Studies of Jounce’s prospect are also continuing, but the likelihood of ICOS living up to hopes are fading. If the studies flop, ICOS will become the latest in a series of targets dating back to IDO to fail to deliver the hoped-for effect on immuno-oncology agents.