Revolution Medicines touts ‘unprecedented’ data in pancreatic cancer trial

Metastatic pancreatic cancer patients who received a targeted pill from Revolution Medicines lived nearly twice as long as patients who received chemotherapy, a striking result in a notoriously deadly and intractable malignancy.

The company said the results released this morning, from a Phase 3 trial, will be used to apply for approval, although it did not say when, STAT's Jason Mast writes

The therapy, daraxonrasib, works by binding to both KRAS and another protein in the cell to form a three-part complex that shuts down KRAS and cuts off a central survival mechanism for the tumor. “These are truly unprecedented overall survival results,” said Revolution Medicines CEO Mark Goldsmith, adding, “This study is significantly elevating the survival bar in one of the deadliest human cancers.”

cancer

Allogene's off-the-shelf CAR-T clears residual disease

Allogene Therapeutics reported early Phase 3 data suggesting its off-the-shelf CAR-T therapy cema-cel could meaningfully reduce relapse risk in B-cell lymphoma, STAT’s Adam Feuerstein writes. More than half the treated patients achieved minimal residual disease, versus 16% who were observed but not treated. This is a wider gap than analysts expected.

The approach targeted patients who appear in remission after a combination of rituximab and chemotherapy, or R-CHOP, but still harbor microscopic disease. The aim was to intervene earlier than current CAR-Ts from Gilead Sciences and Bristol Myers Squibb, which are largely used later on in a patient’s treatment course.

“These interim data suggest that an off-the-shelf CAR-T may be able to intervene during that important window before clinical relapse to eliminate residual disease and make earlier intervention feasible in routine clinical practice,” Allogene's chief medical officer, Zachary Roberts, said in a statement.

cancer

GSK advancing ovarian cancer drug mo-rez

From STAT’s Andrew Joseph: GSK over the weekend presented data from an experimental cancer drug in an early-stage test, saying the results were so promising that it is launching five Phase 3 trials of the medicine this year, as GSK looks to build on its reemergence in oncology.

In a Phase 1 trial, the drug, known as mo-rez, led to a 62% overall response rate among patients with a form of ovarian cancer, and a 67% response rate in endometrial cancer, according to results presented at a Society of Gynecologic Oncology meeting on Sunday. The most common serious side effects included a decrease in a white blood cell type and anemia, but the dropout rate from adverse events was low, at 2% in the ovarian cancer arm and 4% in the endometrial cancer arm.

“These are patients who have received at least one to three prior lines of therapy … so it is quite a difficult-to-treat patient population,” Hesham Abdullah, GSK’s head of oncology R&D, told reporters. “Being able to see this type of clinical activity and these response rates, which are confirmed, is extremely exciting.”

Mo-rez is an antibody-drug conjugate that GSK picked up through a licensing deal with the Chinese firm Hansoh Pharma. Abdullah said that the drug fit with the focus of GSK, which only returned to oncology in the past decade, in gynecologic cancers. The U.K. company’s checkpoint inhibitor Jemperli, for instance, is approved in endometrial cancer.

GSK’s confidence in the therapy — with plans to launch Phase 3 trials in five different indications in ovarian and endometrial cancers, both as a later-line and a first-line therapy — stemmed from the outcomes in the new trial as well as initial data from Hansoh’s own studies, Abdullah said. But he also sought to frame the company’s strategy for mo-rez as reflecting a faster, more agile GSK under Luke Miels, who took over as CEO in January, succeeding Emma Walmsley.

“You’re also seeing some of that come to life through the development programs, and the confidence that he has in the science and the organization,” Abdullah said, adding that, “It has been reflected in the type of pace that you are seeing and the type of conviction that we have in our programs moving forward.”

bowel disease

Spyre's IBD drug shows early competitive edge

Spyre Therapeutics had its first major showing of meaningful ulcerative colitis data, demonstrating its drug SPY001 was safe and hit its primary endpoint. The experimental drug drove a 9.2-point drop on a disease activity index, with 40% of patients in remission at 12 weeks, STAT’s Allison DeAngelis writes.

Those numbers put it ahead — at least on paper — of a similar drug from Morphic (now part of Eli Lilly) and in the mix with a crowded field that includes Johnson & Johnson. Spyre is pitching this as part of a broader IBD pipeline across multiple pathways — betting that stacking mechanisms could finally move remission rates meaningfully higher.

REGULATION

FDA biologics chief faces a political survival test

Whoever replaces Vinay Prasad as head of the FDA’s biologics division will walk into an almost untenable job, UC Davis cell biology professor Paul Knoepfler writes in the latest edition of STAT’s Lab Dish column. The new appointee will be caught between maintaining scientific rigor and navigating intense political pressure from figures like Robert F. Kennedy Jr. and Marty Makary.

Prasad’s downfall stemmed less from his data-driven instincts than from a lack of political flexibility, Knoepfler writes. Prasad’s successor may need to bend on evidence standards — potentially approving therapies with limited data — just to survive.

“Given the tumult of Prasad’s tenure and the challenges at hand, there’s a solid chance that nobody will be appointed permanent CBER director for quite some time,” Knoepfler writes.

CANCER

FDA again rejects Replimune's melanoma therapy

The FDA on Friday again rejected Replimune’s therapy RP1 for advanced melanoma, saying the data still don’t provide “substantial evidence” of effectiveness — a sharp blow after the company tried to strengthen its case following a similar rejection last year.

The drug, an engineered virus designed to rev up the immune system against melanoma, was initially rejected in July, based in part on concerns that the effects of Replimune’s drug couldn’t be properly teased out, because the treatment was given alongside Opdivo.

A rejection letter posted by the agency Friday reiterated that concern, while listing a litany of others, including some related to how Replimune measured patient response and tumor shrinkage.