Why Celcuity's REVTORPYK Creates A New Path For Precision Oncology
By Erin Harris, Editor-In-Chief, Cell & Gene
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The FDA’s recent approval of Celcuity’s REVTORPYK marks an important milestone in the treatment of HR+/HER2- advanced breast cancer. The therapy is the first FDA-approved inhibitor to comprehensively target all class I PI3K isoforms as well as mTORC1 and mTORC2, offering a new approach to a pathway that has challenged drug developers for nearly two decades. Dr. Erica Stringer-Reasor, Assistant Professor of Medicine in the Division of Hematology & Oncology at the University of Alabama at Birmingham and a clinical investigator in the VIKTORIA-1 trial, answered my questions about why the approval is significant for patients with PIK3CA wild-type disease, where REVTORPYK may fit into treatment, and what its development could signal for the future of precision oncology.
REVTORPYK is the first FDA-approved therapy to inhibit class I PI3K isoforms and mTORC1/2. From your perspective, why is this such an important milestone for HR+/HER2- and PIK3CA wild-type breast cancer?
Dr. Stringer-Reasor: REVTORPYK’s approval by the FDA is an incredibly important milestone for HR+/HER2-, PIK3CA wild-type breast cancer because this therapy has potential to be a practice-changing treatment for oncologists and their patients. For the first time, there is a treatment for this subset of patients who had no targeted therapy options after their cancer progressed following first-line treatment. In the VIKTORIA-1 trial, the median progression-free survival with the REVTORPYK triplet (REVTORPYK plus palbociclib and fulvestrant) was 9.3 months versus two months with fulvestrant. This was meaningful improvement in PFS for patients with advanced breast cancer where every week – and month – counts. For patients, an effective treatment can mean more time with their families and loved ones.
For breast cancer treatment in general, REVTORPYK is the first and only FDA-approved comprehensive PI3K/AKT/mTOR (PAM) pathway inhibitor. Until now, available therapies only inhibited a single PAM component, leading to an “escape mechanism” where the cancer cells cross-activate uninhibited components of the PAM pathway. You could think of it as a highway where one lane is blocked off, so the vehicles cross over to other open lanes. This leaves patients vulnerable to treatment resistance and disease progression. REVTORPYK’s comprehensive inhibition of the PAM pathway fully suppresses PAM activity by eliminating the adaptive resistance cross-activation that occurs with single-target inhibitors. This is a real gamechanger for breast cancer treatment.
The VIKTORIA-1 results showed a major progression-free survival benefit for both the triplet and doublet regimens. How should clinicians think about where this therapy fits after endocrine treatment, and what kinds of patients may benefit most?
Dr. Stringer-Reasor: HR+/HER2- breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all breast cancers. Among that subtype, approximately 60% have PIK3CA wild-type disease, making them ineligible for PI3K/AKT-targeted therapies. As a result, patients are often restricted to chemotherapy-based regimens, which creates a large unmet need for a safe and effective therapy, and that’s the gap REVTORPYK fills. For the first time, oncologists have a treatment option that can meaningfully extend the time until disease progression while keeping side effects tolerable and manageable.
This approval is for PIK3CA wild-type disease, which represents a large portion of HR+/HER2- breast cancer. Why has this been such an underserved group, and how might this approval change testing or treatment conversations in practice?
Dr. Stringer-Reasor: The FDA approval of REVTORPYK solves a 20-year challenge in HR+/HER2- advanced breast cancer because it comprehensively blocks the PAM pathway, which single-target inhibitors cannot do. Right now, REVTORPYK is approved for PIK3CA wild-type advanced breast cancer, so it is only available to patients who do not have the PIK3CA mutation. This is determined through testing. However, REVTORPYK was evaluated in the VIKTORIA-1 trial, with patients who do have the PIK3CA mutation. Data presented at ASCO in June 2026 showed similar positive results in PFS. It would be very exciting if, in the future, REVTORPYK receives FDA approval for PIK3CA advanced breast cancer regardless of mutation status.
The pathway REVTORPYK targets has challenged oncology drug developers for nearly two decades. What lessons could it offer for other difficult targets in precision oncology?
Dr. Stringer-Reasor: Since REVTORPYK comprehensively blocks the PAM pathway, it blocks the PI3 kinase pathway as well as the mTOR pathway. With the goal of eliminating tumor cell growth, reducing these pathways could potentially lead to a stronger and more durable treatment response for patients in multiple other cancer types.
More broadly, what should patients and clinicians understand about the safety profile, dosing, and real-world use of REVTORPYK as this new option enters practice?
Dr. Stringer-Reasor: As an oncologist who has participated in the VIKTORIA-1 study, I have treated and monitored multiple patients with REVTORPYK. Overall, REVTORPYK has a well-tolerated profile, with manageable side effects. For stomatitis, I would recommend that patients use a prophylactic mouthwash to minimize discomfort or sores in the mouth. REVTORPYK is administered as an intravenous (IV) infusion on Days 1, 8 and 15 of each 28-day cycle. Oncologists are well versed in the use of IV therapies in the advanced breast cancer setting. While oral therapies may be perceived as convenient, there are meaningful benefits from IV treatments; we know the patient is receiving treatment, we can have more ongoing patient monitoring, and there are regular touchpoints between the patient and physician. The IV formulation likely also contributes to the drug’s favorable safety profile because IV delivery avoids the continuous gastrointestinal and hepatic exposure associated with oral pan-PI3K/mTOR inhibitors and reduces toxicity-driven healthcare utilization. Overall, I don’t think the route of administration is a limiting factor because REVTORPYK is providing patients with significantly longer time to disease progression with a better safety profile.