Bristol Myers Squibb and Ideaya Biosciences both released detailed snapshots of early-stage data for cancer drugs targeting solid tumors with a certain mutation known as MTAP deletion.
There are no approved therapies specifically for MTAP deletions, though these tumors can be found in a wide range of cancer types, such as urothelial, lung, pancreatic and others. Either drug would allow patients an additional option if they end up resistant to other therapies like checkpoint inhibitors.
While the companies are separately working to treat the same kinds of cancer mutations, their drugs act differently. Bristol Myers’ program, called BMS-986504, is a next-generation PRMT5 inhibitor that affects the binding of PRMT5 and MTA (the “PRMT5-MTA complex”) in an attempt to avoid off-target toxicity from earlier-in-class drugs.
Ideaya’s therapy, codenamed IDE397, is a MAT2A inhibitor and is designed on the concept of synthetic lethality, where tumors with certain genetic aberrations become dependent on another cellular pathway. By blocking MAT2A, IDE397 can effectively treat patients with MTAP-deletion solid tumors, Ideaya says.
Bristol Myers data
Bristol Myers said Friday that, as of Sept. 19, it enrolled 147 patients, 124 of whom were evaluable for efficacy. Of those patients, 26 achieved a partial response, good for an ORR of 21%.
There were no complete responses, and the median duration of response was 6.9 months, with a median follow-up of 7.6 months. BMS measured seven different dose levels, but did not break down efficacy by each specific dose.
The highest ORR came in mesothelioma, with four of 11 patients achieving a partial response for 36%. Median duration of response was not reached. In NSCLC, eight of 26 patients reached a partial response (31% ORR) with a median duration of response of 10.5 months. Pancreatic ductal adenocarcinoma had the lowest response rate, with five of 33 patients achieving partial response (15%).
Treatment-related side effects were observed in 78% of the 147-patient sample, including 12% who saw grade 3 or higher adverse events. The most common side effects were nausea, vomiting, fatigue, diarrhea and decreased appetite. Additionally, 3% of patients discontinued treatment due to side effects.
Ideaya data
Ideaya’s data build on a July readout from an 18-patient sample. In the new dataset, there are 27 patients evaluable for efficacy as of an Aug. 22 cutoff.
Nine of the 27 patients responded to the therapy, including one complete response and eight partial responses (33% ORR, down from 39% in July). Enrolled patients had either urothelial cancer, squamous NSCLC or adenocarcinoma NSCLC with MTAP deletions.
The median duration of response is still immature, Ideaya said, as is median progression-free survival. The median duration of treatment has also not been reached.
Treatment-related side effects were observed in 54% of patients, including 18% who saw grade 3 or higher adverse events (though none of those observed in more than 5% of patients). The most common side effects were peripheral neuropathy (none at grade 3 or higher), decreased appetite, blood creatinine increase, nausea, fatigue and asthenia.
In addition to the monotherapy, Ideaya is also testing IDE397 with BMS-986504 and an experimental PRMT5 inhibitor from Amgen.
Editor’s note: This story has been updated to correct the data from Bristol Myers, reflecting data from its presentation, not its abstract.