UPDATE: Merck's TIGIT fails in phase 2 Keytruda combo, notching another loss for the class

Merck & Co.'s TIGIT therapy tacked on to Keytruda did not improve progression-free survival in a phase 2 lung cancer trial, marking the latest failure for the class. 

The company reported open-label, phase 2 data Thursday showing that a co-formulation of Keytruda and anti-TIGIT therapy vibostolimab did not improve progression-free survival compared to chemotherapy alone in patients with metastatic non-small cell lung cancer that had previously been treated with immunotherapy and platinum-doublet chemotherapy. Merck said the co-formulation was “numerically less effective” than chemo alone and is recommending to trial investigators that patients in this arm of the trial switch to the standard of care unless physicians feel they're experiencing a benefit. 

Chief Medical Officer Eliav Barr, M.D., was undeterred by the results. 

“I don't think that there's anything that's changed my mind about TIGIT-pembro combos,” he said in an interview with Fierce Biotech. Keytruda is also known as pembrolizumab. “It really is going to be all about phase 3.”

Analysts at SVB Securities said they were "not surprised" by the results, given that the patient population had disease progression after both immunotherapy and chemotherapy. They remained confident that TIGITs have the potential to help patients in earlier lines of treatment or with "cytotoxic mechanisms." 

Blinded arms of the trial testing the co-formulation, called MK-7684A, in addition to chemotherapy compared to chemo alone remain ongoing. 

Still, confidence in the TIGIT class was shaken last year when Roche’s tiragolumab failed in a phase 3 trial last May. The immune receptor has perked the interest of drug developers as a potentially new immunotherapy target, following in the footsteps of PD-1 and PD-L1—the former being the class that blockbuster therapy Keytruda belongs to. Gilead, Novartis and GSK are just a handful of the Big Pharmas that have made bets on the target through partnerships and licensing opportunities. 

For Merck, however, the open-label flop comes amid a whopping 10 ongoing trials testing the co-formulation, which span a number of different cancers and stages. MK-7684A is being tested alone or in combination with other agents in at least 4,000 patients, according to Merck. 

“I think it's fair to say that over the next two to three years, we'll have a lot of readouts … and we'll see what the field shows,” Barr said.

Barr added that Merck is not investing as much in other co-formulations of Keytruda with other immuno-oncology targets and that TIGIT seems to be the most promising. 

Editor's note: This story was updated to include an analyst note from SVB Securities.