ESMO: Relay spotlights expanded FGFR2 inhibitor data it hopes will pave accelerated approval

Grading or assessing a response rate to particular cancer therapies is admittedly an objective task. It depends on the type of cancer, the line of treatment, the dose, the side effects, and on and on. But when you near 90%, you tend to turn heads no matter the context.

Relay Therapeutics has done just that with its FGR2 inhibitor, with results that validate much of the company’s looming regulatory plans. The company presented new data at the European Society of Medical Oncology showing an 88.2% objective response rate at the expected phase 2 dose level of its FGR2 inhibitor, RLY-4008. Out of 17 patients treated with 70mg of the oral small molecule, 15 had an objective response, all of whom had an ongoing response as of the data cutoff date at the beginning of August. All 17 patients reported disease control. 

The data presented at ESMO mark the first look at the company’s expanded trial, a decision that came following Relay’s end-of-phase-1 meeting with the FDA earlier this year. In that meeting, the two agreed there was a pathway to accelerated approval for patients with bile duct cancer, prompting the trial expansion. In October 2021, the company released interim phase 1 data in October 2021 showing that approximately 80% of patients reported reductions in tumor size by the data cutoff date.  

The company is now looking at a number of different cohorts of patients with this cancer depending on their prior treatment status. The cohort examined for this data includes patients who had previously received chemotherapy but not an FGR2 inhibitor.

In an interview with Fierce Biotech, the company’s leaders took a brief victory lap. “I mean, look, we're six-plus years into this,” said CEO Sanjiv Patel, M.D. “And so over that time, you know, we started to build stepping stones towards what we saw at ESMO this week.” 

The additional cohorts being enrolled include one 50-patient group made up of bile duct cancer patients who have the distinct FGFR2 fusion marker the company is honing in on and who have previously been treated with a FGFR2 inhibitor. Another 20-person cohort focuses on patients with the gene marker but who are completely treatment naive. And a third looks at patients with bile duct cancer who have different mutations than the FGFR2 fusion. 

The decision to expand the trial, and include treatment-naive patients, points to a potential example of the FDA’s latest strategy to more quickly advance treatments into earlier lines of therapy. Although Relay’s initial plans are to pursue patients pre-treated with chemo, the company is optimistic that the positive results will translate further. 

“[W]e certainly, I think, are encouraged by the data we've seen in the chemotherapy-treated patient populations and would be hopeful that we'd see these data translate into earlier patients as well,” said Don Bergstrom, M.D., Ph.D., president of R&D. The company has not yet provided a timeline for when it expects to complete enrollment of the expanded trial. 

And while the company is far from crossing both the clinical and regulatory finish lines, the reality is that the market for bile duct therapies is relatively small. Roughly 8,000 new cases are diagnosed a year, just more than 3% of the number of new lung cancer cases reported each year, for example. With that said, an approved cancer treatment is always a milestone. Additionally, three cohorts in the phase 1/2 trial are patients with solid tumors other than bile duct cancer that have FGFR2-related genomics. 

Relay’s leaders wouldn’t say whether or not the company had been approached by buyers for the asset, with Patel saying that over the years, the company has had “lots of engagement with different companies” and that as of now, it holds the global rights. 

The company is also loaded with cash, reporting $838 million on hand in its second-quarter earnings report. Relay forecasted that extends its cash runway into at least 2025. When asked whether that runway calculation took into account the need for potentially scaling up a commercial operation, Patel said the total gives the company “the flexibility to get to the end.

“And so it gives us a lot of strategic freedom,” he said.