Unexpected regulatory updates from Replimune, Summit Therapeutics

From STAT's Adam Feuerstein: Let's start with Replimune, which said this morning the Food and Drug Administration will review RP1, its therapy for advanced melanoma, for a second time, based on a resubmission that included additional data and analysis from a completed clinical trial. The new approval decision date is April 10.

The FDA rejected Replimune's initial RP1 application in July following a contentious review. Rick Pazdur, the FDA's top cancer drug regulator, interceded to block the therapy's approval over the recommendations of some of the agency's staff.

Also this morning, Summit Therapeutics said it would submit an application to the FDA later this quarter seeking the approval of its drug ivonescimab for the treatment of EGFR mutated non-small cell lung cancer.

This submission is also noteworthy. It will be based on a clinical trial called HARMONi in which ivonescimab significantly slowed tumor progression but failed to prolong overall survival. Based on these results, the FDA told Summit that an approval filing was not recommended. Summit has decided to submit the drug, anyway.

vaccines

mRNA Covid shots may amplify immunotherapy

A retrospective study from MD Anderson presented at ESMO suggests mRNA Covid vaccines from Pfizer-BioNTech or Moderna could enhance the effectiveness of immunotherapy drugs, nearly doubling survival in some cancer patients, STAT's Angus Chen reports. Among lung cancer patients, those vaccinated within 100 days before treatment lived a median 37.3 months versus 20.6 months for the unvaccinated.

Researchers believe vaccine-triggered interferon responses may help immune cells better attack tumors, echoing findings from mouse studies. Though preliminary, experts are calling the work "provocative" and "compelling."

"When I first heard about it, I said, 'Wow, seems unlikely,'" said Ryan Sullivan, an immunologist and cancer researcher at Mass General Cancer Center who did not work on the study. "But as I see the data, I think it's more and more compelling. Obviously, it's retrospective data, and needs to be validated."

BREAST CANCER

Enhertu's early use could signal new paradigm in breast cancer

AstraZeneca and Daiichi Sankyo unveiled two pivotal trials showing that their antibody-drug conjugate Enhertu, already a blockbuster in advanced breast cancer, can drive powerful benefits when used earlier — potentially boosting cure rates.

In data presented at ESMO, 67% of HER2-positive patients given Enhertu before surgery had complete responses, versus 56% on chemo, while DESTINY-Breast05 showed a 53% reduction in recurrence or death risk compared to Kadcyla after surgery. Though interstitial lung disease remains a concern, rates were largely low and manageable.

"Daiichi Sankyo sees this meeting as kind of a capstone moment for this entire Enhertu program," Ken Keller, the head of the company's global oncology business, told STAT's Andrew Joseph. "This is what we hoped the program would do six, seven years ago when we designed it, and it worked."

liquid biopsies

Grail's Galleri cancer test gains ground, but doubts linger

Grail unveiled new data from its 36,000-person Pathfinder 2 trial at ESMO that showed that its blood-based cancer test, Galleri, detected roughly 40% of cancers — many of them types not currently screened for — with a 62% positive predictive value, marking a clear improvement over earlier studies.

That said, it's still unclear whether Galleri actually catches tumors earlier than existing methods or meaningfully improves survival, STAT's Jonathan Wosen writes.

"It's very difficult to judge the clinical importance of these results," a Fred Hutchinson biostatistician who studies cancer screening, told STAT. "The extent to which the fate of these cancers is being changed by being diagnosed by the test is unclear."

The results bolster Grail's planned FDA submission by mid-2026, even as the biotech faces mounting competition from Exact Sciences and Guardant Health — and ongoing questions about whether liquid biopsy screening can truly change cancer outcomes.

BREAST CANCER

AstraZeneca, Gilead vie with new breast cancer ADCs

Two long-awaited antibody-drug conjugates from AstraZeneca and Gilead have each delivered wins in first-line metastatic triple-negative breast cancer, giving oncologists long-sought alternatives to chemo.

AstraZeneca's Datroway, which was developed with Daiichi Sankyo, cut the risk of death by 21% and doubled median progression-free survival to nearly 11 months. Meanwhile, Gilead's Trodelvy extended progression-free survival to 9.7 months with fewer patients dropping out of the study.

"We feel this is a really important result for patients," Dietmar Berger, Gilead's chief medical officer, told STAT's Andrew Joseph.

Datroway's overall survival edge and cleaner safety profile drew louder applause at ESMO, with lower rates of serious or more severe side effects. Trodelvy, meanwhile, led to more infection-linked deaths due to neutropenia, a condition caused by a drop in white blood cell levels.

As precision ADCs grow more lucrative and are starting to supplant traditional chemotherapies, clinicians say it'll come down to real-world side effects to guide their choice between Datroway and Trodelvy.

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