Last updated: July 29, 2026
Gedatolisib (Revtorpyk, PF-05212384, formerly PKI-587) is the first-in-class intravenous small-molecule pan-PI3K/mTOR inhibitor, developed by Celcuity. It was FDA-approved on July 14, 2026, in combination with fulvestrant, with or without palbociclib, for adults with HR-positive, HER2-negative, PIK3CA wild-type locally advanced or metastatic breast cancer after progression on or after at least one line of endocrine therapy in the metastatic setting. It is administered by intravenous infusion.
Mechanism of action:Gedatolisib blocks the PI3K/AKT/mTOR (PAM) pathway — one of the most common growth-and-survival pathways in cancer — at multiple nodes simultaneously. It inhibits all Class I PI3K isoforms (both wild-type and mutant PI3Kα, plus PI3Kβ, γ, and δ) as well as both mTOR complexes (mTORC1 and mTORC2). Single-node pathway inhibitors can be bypassed when the tumor compensates through a parallel PI3K isoform or mTOR complex; by hitting several nodes at once, gedatolisib is designed to reduce that adaptive resistance.
Regulatory status:FDA-approved July 14, 2026 (brand name Revtorpyk) for HR+/HER2-, PIK3CA wild-type advanced breast cancer after ≥1 line of endocrine therapy, with fulvestrant ± palbociclib — based on the Phase 3 VIKTORIA-1 trial. Endometrial cancer and metastatic castration-resistant prostate cancer are investigational (trials ongoing, not FDA-approved). A supplemental application for the PIK3CA-mutant cohort of VIKTORIA-1 was planned for Q3 2026.
Most HR-positive, HER2-negative breast cancers eventually stop responding to hormone therapy and CDK4/6 inhibitors like palbociclib. A major reason is the PI3K/AKT/mTOR pathway — a growth signal that tumors switch on to escape treatment. Until now, the drugs that target this pathway (alpelisib, inavolisib, capivasertib) only helped patients whose tumors carry a specific mutation in PIK3CA, AKT1, or PTEN. That left out the roughly 60% of patients whose tumors are “PIK3CA wild-type” (no such mutation) — they had no pathway-targeted option.
Gedatolisib is the first to change that. Instead of blocking one point in the pathway, it blocks several at once (all the main PI3K forms plus mTOR). That broader mechanism means it can work whether or not the tumor has a PIK3CA mutation — and its July 2026 FDA approval is specifically for the PIK3CA wild-type group that previously had nothing in this class.
What the trial showed. In the Phase 3 VIKTORIA-1 study, adding gedatolisib to standard fulvestrant (with or without palbociclib) substantially delayed cancer progression compared with fulvestrant alone in PIK3CA wild-type disease — the basis for the approval. It is given as an intravenous infusion rather than a daily pill.
Gedatolisib has 1 active FDA approval, anchored in the PIK3CA wild-type HR+/HER2- breast-cancer population.
HR+/HER2-, PIK3CA Wild-Type Advanced Breast Cancer, with Fulvestrant ± Palbociclib (VIKTORIA-1)
★ First-in-Class: Multi-Node PI3K/mTOR Inhibition for the PIK3CA Wild-Type Majority
The approved PI3K-pathway drugs before gedatolisib each hit a single node and are used mainly in biomarker-selected, mutation-positive disease: alpelisib (Piqray) and inavolisib (Itovebi) target PI3Kα in PIK3CA-mutant tumors; capivasertib (Truqap) targets AKT in PIK3CA/AKT1/PTEN-altered tumors; everolimus targets mTOR. Gedatolisib inhibits the pathway at multiple nodes (pan-PI3K plus both mTOR complexes), which is why it retains activity in PIK3CA wild-type disease — the population its FDA approval uniquely covers.
The mechanistic rationale for multi-node inhibition is reduced adaptive resistance: blocking one node often lets the tumor compensate through a parallel PI3K isoform or the other mTOR complex, whereas hitting several nodes at once closes those escape routes. The trade-off is that gedatolisib is an intravenous infusion rather than an oral pill, and PI3K/mTOR-pathway inhibition carries characteristic on-mechanism side effects (see below).
Curated set of recruiting interventional gedatolisib / Revtorpyk / PF-05212384 trials in the ClinTrialFinder corpus as of July 2026 (3 recruiting interventional trials), grouped by setting. Note: the registrational VIKTORIA-1 trial that supported the July 2026 approval is complete and is described above as the approval basis; the trials below are those currently recruiting.
The PI3K/AKT/mTOR (PAM) pathway transmits growth and survival signals from the cell surface to the nucleus and is one of the most frequently activated pathways in HR+/HER2- breast cancer, especially after endocrine therapy and CDK4/6 inhibitors. Gedatolisib binds the ATP sites of all Class I PI3K isoforms (wild-type and mutant PI3Kα, plus PI3Kβ, γ, δ) and of both mTOR complexes (mTORC1 and mTORC2). By inhibiting the pathway at several nodes simultaneously, it aims to prevent the compensatory feedback reactivation that limits single-node inhibitors — the mechanistic reason it can act in PIK3CA wild-type tumors, not only mutation-selected ones.
On-Mechanism PI3K/mTOR Pathway Effects
Inhibiting the PI3K/AKT/mTOR pathway carries characteristic, on-target side effects. Because PI3Kα also relays the body's insulin signal, hyperglycemia (high blood sugar) is a hallmark class effect and is monitored during treatment. Stomatitis / mucositis (mouth sores, an mTOR-associated effect), rash, diarrhea, nausea, and fatigue are also commonly associated with this drug class. Gedatolisib is given by intravenous infusion. Refer to the FDA prescribing information for the complete, gedatolisib-specific safety profile, monitoring, and dose-modification guidance.
These considerations are general to the PI3K/AKT/mTOR pathway class and are not a substitute for the approved label. Your oncology team manages blood-sugar monitoring, oral care, and any dose adjustments based on the official prescribing information and your individual situation.
In HR+/HER2- advanced breast cancer, gedatolisib's approved position is after progression on at least one line of endocrine therapy in the metastatic setting — typically after a first-line CDK4/6 inhibitor (such as palbociclib) plus endocrine therapy — combined with fulvestrant, with or without palbociclib, in PIK3CA wild-type disease. This complements the mutation-selected pathway options (alpelisib, inavolisib, capivasertib) used in PIK3CA/AKT1/PTEN-altered tumors. The VIKTORIA-2 trial is testing whether gedatolisib can move into the first-line setting. For the class context of CDK4/6 inhibitor backbones, see the CDK4/6 Inhibitors hub; for the disease-level view, see the breast cancer trials page.
What is gedatolisib (Revtorpyk) and how does it work?
Gedatolisib (Revtorpyk, PF-05212384) is the first-in-class intravenous pan-PI3K/mTOR inhibitor from Celcuity. It blocks the PI3K/AKT/mTOR (PAM) growth pathway at multiple nodes at once — inhibiting all Class I PI3K isoforms (wild-type and mutant PI3Kα, plus β, γ, δ) and both mTOR complexes (mTORC1 and mTORC2). Because single-node pathway inhibitors can be bypassed by compensatory signaling, multi-node inhibition is designed to reduce that adaptive resistance. It is given by intravenous infusion.
What is gedatolisib FDA-approved for?
On July 14, 2026, the FDA approved gedatolisib with fulvestrant, with or without palbociclib, for adults with HR-positive, HER2-negative, PIK3CA wild-type (no PIK3CA mutation detected) locally advanced or metastatic breast cancer that has progressed on or after at least one line of endocrine therapy in the metastatic setting. It is the first PI3K/AKT/mTOR pathway drug approved specifically for the PIK3CA wild-type population.
What were the VIKTORIA-1 results?
In the Phase 3 VIKTORIA-1 trial (PIK3CA wild-type cohort), gedatolisib + palbociclib + fulvestrant reached a median progression-free survival of 9.3 months vs 2.0 months with fulvestrant alone (hazard ratio 0.24, a 76% reduction in the risk of progression or death), and gedatolisib + fulvestrant reached 7.4 vs 2.0 months (hazard ratio 0.33, a 67% reduction). In the separate PIK3CA-mutant cohort, the gedatolisib doublet reached 11.3 vs 5.6 months with alpelisib + fulvestrant.
How is gedatolisib different from alpelisib, inavolisib, and capivasertib?
Alpelisib (Piqray), inavolisib (Itovebi), capivasertib (Truqap), and everolimus each target a single node of the PI3K/AKT/mTOR pathway and are used mainly in PIK3CA-, AKT1-, or PTEN-altered disease. Gedatolisib inhibits multiple nodes (pan-PI3K plus mTOR) and is the first pathway drug approved for the PIK3CA wild-type population, which had no targeted option before. It is also intravenous, whereas the single-node inhibitors are oral.
Is gedatolisib being studied beyond breast cancer?
Yes. Recruiting trials include VIKTORIA-2 (NCT06757634), a Phase 3 study in first-line HR+/HER2- advanced breast cancer; RESOLVE (NCT03675893), a Phase 2 study of gedatolisib with abemaciclib/letrozole (with or without metformin) in ER-positive endometrial cancer; and a Phase 1/2 study of gedatolisib plus darolutamide in metastatic castration-resistant prostate cancer (NCT06190899).
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