SITC18: Merck highlights new LAG-3 and TIGIT data

Cancer in newspaper clipping
Studies show acceptable safety profiles with no dose-limiting toxicities and early signals of antitumor activity, says Merck. (PDPics/Pixabay)

The SITC conference kicked off Wednesday with a stack of new data on immuno-oncology drugs, including a first look at Merck & Co.’s early-stage drugs targeting LAG-3 and TIGIT.

While the PD-1/PD-L1 checkpoint inhibitors that hit the market in 2015 have already transformed the standard of care in some cancers—at least for some patients—there is still a sizable proportion who don’t respond to them, and the hunt is on for new drugs and combinations that can improve cancer immunotherapy.

That’s the thinking behind two Merck programs that are on display at the SITC (Society for Immunotherapy of Cancer) conference in Washington, D.C., this week, which both target inhibitory receptors involved in blocking immune responses to tumors.

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Anti-LAG-3 candidate MK-4280 and anti-TIGIT drug MK-7684 have both shown acceptable safety profiles in early studies reported at the conference with “no dose limiting toxicities and early signals of anti-tumor activity … as monotherapies and in combination with Keytruda” in advanced solid tumors, says Merck.

For MK-4280, the initial phase 1/2 readout in 18 patients on monotherapy revealed that one subject (6%) had a partial response (PR) to the drug, which compared to four PRs out of 15 patients (27%) in the combination group. Stabilized disease was seen in 17% and 40% of patients, respectively.

For MK-7684, a phase 1 study involving 34 monotherapy patients and 34 also receiving Keytruda revealed one PR in the group taking the anti-TIGIT drug alone (3%) and eight on the combination (19%) with stable disease seen in 35% and 47% respectively.

Merck’s head of early-stage development in clinical oncology, Eric Rubin, M.D., said the studies are providing “valuable early insights into the antitumor activity for our investigational anti-LAG-3 and anti-TIGIT therapies in patients with advanced and metastatic cancer.”

Also on display at SITC this week is a LAG-3 fusion protein from Immutep (formerly Prima Biomed) called eftilagimod alpha, which is a little further ahead in development as it has started a phase 2 trial in non-small cell lung cancer.

Phase 1 data with the drug plus Keytruda in melanoma are being presented at the conference and show an objective response rate of 33% including one complete response in a patient who had progressed on Keytruda alone. Both Merck and Immutep are playing catch-up with Bristol-Myers Squibb in the LAG-3 category, however, as BMS’ relatlimab is now moving into late-stage development after posting encouraging data at ESMO and ASCO this year.

Merck is also giving a first glimpse at SITC of bispecific antibodies targeting both LAG-3 and PD-1—developed in collaboration with Ablynx—that could deliver combination immunotherapy in a single drug.

There’s more going on with TIGIT as well, with phase 1a/b data presented on OncoMed’s anti-TIGIT antibody etigilimab (OMP-313M32) showing tolerability and early signs of efficacy as a monotherapy, with a 0% overall response rate but 22% stabilized disease.

Meanwhile, there is preclinical data involving TIGIT candidates from iTeos Therapeutics (EOS8844488), I-Mab Biopharma (TJT6) and Arcus Bioscience/Stanton Biosciences (AB154), as well as Aurigene, which is developing dual TIGIT/PD-L1-targeted small-molecule drugs.