Mevrometostat

Pfizer\'s data were slated for a Feb. 13 presentation at the ASCO Genitourinary Cancers Symposium, but the abstract was posted early after a portion of it was shared on the ASCO-GU daily news site.\n After an apparent accidental early release, Pfizer has revealed phase 1 data showing its investigational candidate, alongside Xtandi, reduced prostate cancer progression by 49%.The data, centering an investigational small molecule EZH2 inhibitor called mevrometostat, were initially scheduled for a Feb. 13 presentation at the ASCO Genitourinary Cancers Symposium in San Francisco. However, the abstract was posted early after a portion of it was shared on the ASCO-GU daily news site.The open-label trial enrolled 81 patients with metastatic castration-resistant prostate cancer (mCRPC) who had received prior treatment. For the 41 patients receiving both mevrometostat and Xtandi (enzalutamide), median radiographic progression-free survival was 14.3 months. The result compared with 6.2 months for the 40 patients who received only Xtandi.For the 15 patients who received the investigational combo and had measurable disease at baseline, the overall response (OR) rate was 26.7%. This is compared to a 14.3% OR rate for the 14 eligible patients on enzalutamide.Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 53.7% of patients receiving the combo, with the most common of these events being diarrhea, neutropenia and sepsis. In the monotherapy cohort, 42.5% of patients experienced TEAEs.No treatment-related deaths were reported as of the September 2024 cutoff.   Researchers deemed the combo as improving outcomes and having a manageable safety profile, according to the abstract, which was drafted by Pfizer\'s generative AI tool “MAIA.” The results come from an ongoing dose-escalation and expanded-cohort study that is also testing out the combo among patients with advanced small cell lung cancer and follicular lymphoma.Pfizer has already launched two phase 3 trials to assess mevrometostat and enzalutamide for androgen receptor pathway inhibitor-naïve patients with mCRPC and for patients with mCRPC who have previously received Johnson & Johnson’s Zytiga.Meanwhile, Pfizer also announced a new deal with Boston biotech Alloy Therapeutics aimed at developing a new platform that can discover antibodies to tackle targets that are difficult to access with existing tech.Alloy will receive an upfront payment of an undisclosed amount and will also have the chance to collect certain biobucks payments, according to a Feb. 11 release.Alloy’s ATX-Gx platform is based on a collection of fully humanized transgenic mice and is being used by more than 170 partners, according to the biotech.  The deal expands on an existing partnership between Pfizer and Alloy in which the pair worked together on a range of antibody discovery efforts and leveraged the biotech’s ATX-CLC platform. The science is made to generate human antibodies using a single light chain sequence, according to Alloy.

Clinical trial results from a Phase 1 study by Pfizer leaked days before a late-breaking presentation scheduled for Thursday, showing that the drugmaker’s prostate cancer candidate cut the risk of disease progression by around half when added on top of a hormone therapy. The data were due to be presented Thursday at the ASCO Genitourinary Cancers Symposium in San Francisco. But on Monday morning, Cantor Fitzgerald analysts flagged a leaked article on the confab’s website. The conference organizers subsequently published the full study abstract later on Monday. The results were welcome news for Oric Pharmaceuticals, which saw a surge in analyst interest because it has its own candidate with the same mechanism as Pfizer’s. Pfizer’s open-label Phase 1 trial enrolled 81 people with metastatic castration-resistant prostate cancer. The median progression-free survival was 14.3 months for those who received the experimental drug mevrometostat plus Pfizer’s Xtandi versus 6.2 months for Xtandi alone, according to a company presentation seen by Endpoints News . That means the addition of mevrometostat reduced the risk of disease progression or death by 49% in the data cut as of September. The participants had previously received hormone therapy and at least one round of chemotherapy. The most common side effects seen in the treatment arm included diarrhea, nausea and change in sense of taste. There were no treatment-related deaths, according to Pfizer. Mevrometostat blocks an enzyme called EZH2, which plays a key role in driving castration resistance in prostate cancer. “The goal of the combination is that we are able to extend the benefit of [Xtandi] as well as prevent the emergence of resistance to [Xtandi],” Pfizer’s head of genitourinary cancers development Dana Kennedy told Endpoints in an interview. The drugmaker has already started two Phase 3 studies of the mevrometostat regimen in patients previously treated with hormone therapy (MEVPRO-1) and those who haven’t been treated with androgen receptor pathway inhibitors (MEVPRO-2). On Monday, Pfizer offered more details on the design of MEVPRO-1, which is aiming to enroll around 600 patients and will set the regimen against physician’s choice of enzalutamide or docetaxel. Pfizer hopes to achieve similar results to the Phase 1 in the MEVPRO-1 primary endpoint of PFS, Kennedy said. The trial will also use a “further optimized” 875 mg dose of mevrometostat in contrast to the 1,250 mg dose evaluated in the Phase 1 study, she added. Its primary completion is expected at the end of the year. Oric’s candidate, dubbed ORIC-944, is in Phase 1/2 development for prostate cancer in separate doublets with Johnson & Johnson’s Erleada and Bayer’s Nubeqa. Buoyed by Pfizer’s leaked data, the company’s share price $ORIC was up as much as 15% Monday morning, although it settled before market open Tuesday. Both Pfizer and Oric’s drugs could “offer compelling all-oral doublets for a cancer type that is primarily treated by urologists in early stages,” Stifel analysts said Monday after the data breach. The convenience and safety of the candidates will be key because urologists currently need to refer second-line patients to a medical oncologist or nuclear medicine to get newer, more effective therapies than ARPIs due to their side effects, they added. Oric’s candidate has a longer half-life, which means it offers more convenient daily dosing compared with twice-daily dosing for mevrometostat, Jefferies analysts wrote Monday.