ASCO: Merck’s Keytruda combo data could spark hope for lymphoma patients who lack options

ASCO: Merck’s Keytruda combo data could spark hope for lymphoma patients who lack options

For Merck & Co., the oncology show has been all about Keytruda but also about Lynparza and Lenvima for the past few years. But the New Jersey pharma is hoping to soon have some supporting players to add to the playbill.

“I think sometimes people don’t appreciate the breadth of our pipeline beyond Keytruda,” said Eric Rubin, M.D., senior vice president of early-stage development, clinical oncology, at Merck Research Laboratories.

The company will showcase a few of those hopefuls at the 2022 American Society of Clinical Oncology (ASCO) annual meeting in June.

First up is favezelimab, Merck’s LAG-3-targeting antibody being tested in a phase 1/2 study with, of course, its checkpoint inhibitor Keytruda, in relapsed or refractory classical Hodgkin lymphoma. The patients had up to four lines of previous therapy, with the analysis focused on those who had not previously received a PD-1 like Keytruda.

The study confirmed what Merck has previously found: that adding an anti-LAG3 boosted Keytruda’s efficacy, this time in lymphoma. Similar results were found when the pair was tested in colon cancer, which was presented at last year’s ASCO conference.

This time around in the lymphoma study, favezelimab and Keytruda spurred an overall response rate of 73%, with a complete response rate of 27% and partial responses clocking in at 47%. Lesion reductions were seen in 28 of the 30 patients who were eligible for evaluation as of the data cutoff.

Another study to be presented at ASCO was based on patients with a high unmet need, according to Rubin: those who had progressed on a PD-1 therapy like Keytruda. This population doesn’t really have a standard of care at all, he said. This group had about a 30% overall response rate to the favezelimab-Keytruda combo at 16.5 months, including 24% partial response and 7% complete response. Out of 29 patients evaluated, 23 had a reduction from baseline in target lesions.

“We’re quite excited about the possibility of helping patients with that unmet need with PD-1 refractory disease,” Rubin said.

Based on that information, Merck will soon advance the combo into a phase 3 study for this population.

In the PD-1-naïve population, Rubin said there are still more questions to be answered.

“We will have to keep an eye as the data mature to decide if we think in that population, there’s sufficient improvement to warrant registration leverage there,” he said.

One possibility could be adding in other therapies to the combo, such as the anti-TIGIT therapy vibostolimab or the antibody-drug conjugate zilovertamab vedotin.

As for safety, Rubin said the profile was similar to Keytruda alone. That’s another positive aspect of the combination, “that you seem to get additional efficacy really without much additional toxicity,” he said.

In the PD-1-naïve study, 12 patients out of the 30 discontinued treatment due to adverse events or disease progression. Treatment-related adverse events occurred in 26 patients, or 87%, with seven patients reporting grades 3 or 4, which are more severe events. Serious treatment-related events occurred in four patients. The most common adverse events were hypothyroidism, infusion-related reactions and fatigue. The more serious events reported included autoimmune hepatitis, digestive tract inflammation and thrombocytopenia, which is when platelet counts fall too low.

Other information Merck will present at ASCO include first-in-human data on the anti–ILT3 monoclonal antibody MK-0482 alone and in combo with Keytruda in solid tumors. MK-0482 is from one of 20 agents that Merck has in early or preclinical research, Rubin noted.

MK-0482 targets the myeloid suppressive pathways. The therapy was well tolerated, and Merck now has a dose to move forward thanks to the phase 1 results. However, Rubin said they did not see any response in the monotherapy portion of the study, but responses across a number of tumor types were seen in the Keytruda combo. Merck plans to explore additional patient groups and specific tumor types with the combination.

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