How sub can you subset? Erasca shores up case for testing its two lead candidates in combo

It’s challenging enough to get one cancer drug approved.

But it looks like Erasca is gunning for its two lead candidates in combination — though both are still in very early stages.

In its Q2 report, the San Diego-based biotech said it would read out initial results on its two lead candidates later in the year. And Erasca did just that Wednesday, but rather than presenting the results of the two Phase I monotherapy trials separately, Erasca touted a pooled analysis of its two ongoing trials — one for ERAS-007, the ERK1/2 inhibitor Erasca licensed from Asana BioSciences, and one for ERAS-601, an SHP2 inhibitor — plus a past Asana trial of ERAS-007.

Rather than specific tissues, Erasca’s whole play surrounds the RAS/MAPK pathway, a major pathway when it comes to cancer (mutations to KRAS, one part of the pathway, may be found in a quarter of all cancers). In the pooled analysis, Erasca separated patients with RAS/MAPK mutations into two groups — colorectal cancer (CRC) and non-colorectal cancer (non-CRC). In the CRC group, no responses to either drug were observed in eight patients, according to Erasca’s presentation.

In the non-CRC group, 6 of 26 patients (23%) had partial responses to either ERAS-007 or ERAS-601. Of those six responders, two had confirmed responses, while four had unconfirmed responses. Breaking it down even further, in a subset of patients with mutations in BRAF, which is another part along the RAS/MAPK pathway, four of nine had a partial response to one of the candidates.

Both Erasca drugs target parts of the RAS/MAPK pathway — ERAS-601 works upstream of RAS, while ERAS-007 works downstream.

Wei Lin

“What we have learned from other targeted therapies is that combinations are the best approach to provide durable treatment responses in patients with RAS/MAPK alterations,” Erasca’s CMO Wei Lin said in a statement.

In the press release, Erasca also said that the analysis was meant to “identify responsive subsets that were particularly sensitive to ERAS-007 or ERAS-601 for prioritized combination development.”

In terms of safety, ERAS-601 caused two cases of grade 4 adverse events — anemia and hypertensive encephalopathy. Erasca said that the safety profiles of the two drugs didn’t overlap too much — a concern for combo therapies — noting diarrhea as the one potentially overlapping toxicity.

Erasca plans to begin a dose escalation trial for the combo of ERAS-007 and ERAS-601 in the first half of next year, Erasca CEO and co-founder Jonathan Lim said in the press release.

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