With good-but-not-great updated data on its approved oncology combo of avutometinib plus defactinib (A+D) in first-line metastatic pancreatic cancer, Verastem Oncology will now channel its primary R&D efforts toward other pipeline darlings.
The updated phase 1b/2a data on A+D—which snared Verastem its first approval last year as an ovarian cancer combo regimen named Avmapki and Fakzynja—tied the company’s combo to a 52% objective response rate (ORR) in previously-untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
Those results, while “decent” and “encouragingly in the ballpark” of a 58% ORR seen in testing of Revolution Medicines’ rival asset daraxonrasib, signal a downturn from the 83% ORR Verastem reported last year, analysts at Mizuho Securities wrote in a Jun. 17 note to clients.
The Mizuho team said it figured avutometinib and defactinib could eventually carve out a niche in the PDAC treatment paradigm, but management has now told the analysts that no more resources will be put toward the combo in the pancreatic cancer indication. That confidence in winding down PDAC development internally for A+D is driven in part by Verastem’s belief that another of its pipeline candidates, the KRAS G12D inhibitor VS-7375, holds best-in-class potential, the Mizuho team noted.
In its data announcement Wednesday morning, Verastem CEO Dan Paterson said that the Boston-headquartered company would “continue to evaluate the potential role of avutometinib plus defactinib in metastatic pancreatic cancer.”
That could include “future development opportunities and potential strategic collaborations,” both informed by the final overall survival (OS) results on A+D and emerging data from VS-7375, which Verastem is assessing as both a monotherapy and as part of potential combo regimens in pancreatic cancer, the CEO said.
When reached for comment, a company spokesperson explained to Fierce on Wednesday that, “We are still evaluating things.”
“Further development without investment from a partner would be a high bar given the exciting data emerging for VS-7375,” the spokesperson added.
Still, the company continues to “believe there is a potential role for the drugs in metastatic pancreatic cancer given the data and that the mechanisms are different than other current approaches in the space.”
According to Mizuho, Verastem management told the analysts that it felt its data were strong when stacked against that of Revolution’s candidate or the roughly 30% ORR tied to standard-of-care chemotherapy.
A+D came to fruition through a series of licensing deals, with Verastem first getting its hands on FAK inhibitor defactinib through a Pfizer in-licensing agreement in 2012. The company then picked up rights to RAF/MEK inhibitor avutometinib from Pfizer and Merck KGaA in 2016, specifically looking to pair the asset with defactinib after the prior candidate failed an early-stage trial in mesothelioma.
Meanwhile, In Verastem’s 29-patient PDAC study, patients received avutometinib twice a week, defactinib twice daily for 3 weeks on and one week off, and gemcitabine in tandem with nab-paclitaxel at certain points in the treatment cycle.
With a data cutoff of June 5 allowing for a median follow-up of 9.8 months, Verastem linked its combination regimen to an OS rate of 86% at 6 months, caveating that the overall survival data are “continuing to mature.”
Progression-free survival at the half-year mark landed at 68%, with the confirmed ORR reaching 52%, reflecting 15 out of 29 participants.
With A+D’s FDA approval last May in patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC), Verastem officially entered the commercial realm. At the time, Mizuho analysts pinned peak sales in the indication for the Avmapki-Fakzynja duo between $700 and $900 million.
As of Wednesday, Mizuho reiterated that the Avmapki-Fakzynja combo is a “commercial execution story,” and the fact that the company now has more time to focus on the launch should be viewed as something of a silver lining.