NEW YORK – Ideaya Biosciences is gearing up for future registration-directed clinical trials based on early data suggesting that its MAT2A inhibitor, IDE397, could benefit patients with MTAP-deleted bladder and lung cancer.
On Monday, South San Francisco, California-based Ideaya presented the results of an interim analysis from a Phase II expansion dose cohort in an ongoing trial of IDE397. The study has multiple cohorts in which Ideaya is evaluating IDE397 both as a monotherapy and in combination with various drugs in multiple MTAP-null cancer types. On Monday, Ideaya shared data on IDE397's activity specifically in patients with advanced non-small cell lung or urothelial cancer.
About 15 percent of all solid tumors have a MTAP deletion, Ideaya President and CEO Yujiro Hata said Monday during a conference call to discuss the interim data with investors. But there are no commercially available therapies that target the biomarker. In lung and urothelial cancer, he estimated MTAP deletions are present in more than 15 percent and 25 percent of cases, respectively.
Ideaya shared with investors data from 18 evaluable patients treated with a 30-milligram dose of IDE397. These patients had received a median of two prior therapies before enrolling in the trial. Eleven patients had MTAP-deleted NSCLC, and seven had MTAP-deleted urothelial cancer.
As of a data cutoff of June 21, 39 percent of the 18 patients had responded to the drug. One patient had a complete response, and six patients had partial responses. The median duration of response and the median progression-free survival outcomes haven't been reached. Investigators are still waiting to confirm two additional responses, but as of the data cutoff, only one patient had experienced disease progression on IDE397.
Ideaya Chief Medical Officer Darrin Beaupre highlighted during Monday's call that when patients underwent biomarker testing to determine trial eligibility, Ideaya found MTAP deletions in 25 percent of NSCLC patients and 50 percent of urothelial cancer patients screened, which was higher than the frequency reported in The Cancer Genome Atlas.
Ideaya also assessed IDE397's effect on patients' circulating tumor DNA. Of 16 patients who were evaluable for ctDNA, all experienced some reduction, and 81 percent achieved a molecular response, which investigators defined as a 50 percent reduction in ctDNA from baseline.
The majority of adverse events were low grade, Beaupre said. None of the patients experienced drug-related serious adverse events or had to discontinue IDE397 due to treatment side effects.
"This cumulative data," Beaupre said, "provides evidence of proof of concept for the first-in-class MAT2A inhibitor in the setting of lung or urothelial cancer."
In light of this encouraging dose-escalation data, Hata said that Ideaya wants to refine its regulatory strategy for its drug. "Based on today's clinical data update and the emerging clinical efficacy of IDE397 in MTAP deletion solid tumors, one of the primary objectives for the program will be to target development of a registrational plan for the IDE397 program in 2025," he said.
The first setting for which Ideaya pursues commercial approval, however, might not be a monotherapy indication. Indeed, the firm recently inked two partnerships — one with Amgen and one with Gilead — that could lead to combination regimens with better efficacy in MTAP-null cancers than IDE397 alone.
With Amgen, Ideaya is evaluating IDE397 with the PRMT4 inhibitor AMG193 in MTAP-null solid tumors. With Gilead, the firm is evaluating IDE397 with the TROP2-directed antibody-drug conjugate Trodelvy (sacituzumab govitecan) in MTAP-deleted urothelial cancer.
Additionally, Hata said that Ideaya has a second internally developed drug candidate that it intends to combine with IDE397, so that it can advance a wholly owned combination regimen. The firm plans to nominate this second development candidate in the second half of 2024.
"Combinations are our best path forward in terms of depth and durability of response," Beaupre said. "But we've always been aware that if we're in the right tumors, there was potential monotherapy activity." Depending on how the data reads out in the upcoming months, he said Ideaya could advance one of the IDE397 combinations it is partnering on through regulatory review or stick with the monotherapy strategy.
"We're still very early in the game to be quite honest," Beaupre said. "We want to enroll more patients with these indications, provide more monotherapy to them, and continue to monitor the response rate as well as the duration of response. In terms of a regulatory path, it could be multipronged."
So far, Ideaya has enrolled 50 patients into its clinical trial, which includes two cohorts testing combinations with Trodelvy. With Amgen, Ideaya is conducting a Phase I/II trial testing IDE397 with AMG193 and will pursue a joint strategy for publishing the data this year.
"We think the data that was shared today in monotherapy speaks for itself," Hata said. "But at least our internal [data] expectations for the combo [regimens] are higher."
While Hata expects the addition of the MAT2A inhibitor to both Gilead's and Amgen's drugs will enhance the depth and durability of responses compared to taking these drugs alone, he noted that Gilead has already shown data suggesting patients on IDE397 and Trodelvy see a higher benefit than with just Trodelvy.
Beyond urothelial cancer and NSCLC, Ideaya is also exploring the potential for IDE397 in MTAP-deleted pancreatic, head and neck, gastric, and esophageal cancers.