Checkmate's I-O combo reverses PD-1 resistance in melanoma patients

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Checkmate aims to generate data for CMP-001 in other tumor types, including lung cancer. (Rudy and Peter Skitterians)

Checkmate Pharmaceuticals unveiled phase 1 data at AACR showing its lead asset, CMP-001, in combination with Merck’s Keytruda, reversed PD-1 resistance in advanced melanoma patients who had already failed a prior anti-PD-1 treatment.

The trial involved 85 patients whose cancer had progressed on a median of two prior treatments. Of those patients, 44 were enrolled in the dose escalation phase, with the remaining 41 in the expansion phase.

The patients received CMP-001 injections in one or more accessible tumors. Data from 69 patients in the intent to treat population showed a 22% objective response rate. Two patients had a complete response and 13 had a partial response, the company said.

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The 22% response rate is a “significant improvement,” said Checkmate CEO Art Krieg.

“The analysis includes all patients in the trial, including inactive dose groups. […] I don’t see a lot of companies at our stage showing a whole data set—you can cherry pick the data and come up with a higher response rate, but the 22% is for all comers. I think it’s very difficult to look at the data and not say this is an active drug,” he said.

And the durability of the response, he said, is “striking.” Six of the responders maintained their response over six months; of them, two still had a response at 84 weeks.

RELATED: Checkmate raises $27M, adds operations veteran as I-O program gathers pace

While the investigators saw a response in the injected tumors, they also found that the treatment affected noninjected ones, including metastases in the liver, spleen and lungs, “showing more convincingly than has been shown in the past that a local therapy can achieve systemic efficacy,” Krieg said.

Next up, the company hopes to translate its results in melanoma to other tumor types—it already has a lung cancer trial underway. But its strategy as a company has always been to be acquired, Krieg said.

“Our strategy is to generate data in other tumor types and see who is excited about this,” he said. And because there’s so much interest in combo therapies and so much M&A in the immuno-oncology space, he’s not sure Checkmate will get the chance to generate that data before getting snapped up.

Checkpoint inhibitors like Keytruda have seen success in certain cancers but they don’t work for everyone—hence the profusion of companies working on agents to administer alongside these drugs and boost their efficacy.

Checkmate’s CMP-001 does this by activating innate immunity to turn “cold” tumors, which do not respond to anti-PD-1 drugs, into “hot” ones. The molecule is a toll-like receptor 9 (TLR9) agonist encapsulated in a virus-like particle. It activates TLR9 in a particular type of dendritic cell within tumors, ramping up the expression of tumor antigens and calling forth a T-cell response.

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