New IV Treatment for Advanced Hormone-Positive Breast Cancer

Revtorpyk (gedatolisib; Patient Information pronunciation rev-tor-pik) is a kinase inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2, with downstream effects that include AKT pathway inhibition. On company / FDA materials it is described as the only FDA-approved inhibitor that hits all class I PI3K isoforms and both mTOR complexes. It is given as a lyophilized powder for reconstitution, then IV infusion — not an oral tablet.

The FDA approved NDA 219908 on 14 July 2026 (Novel Drug Approvals for 2026 table row 25). Approval letter signed R. Angelo de Claro, MD (Romeo A. de Claro), Director, Office of Oncologic Diseases, OND/CDER (electronic signature 14 Jul 2026 14:02:37). NDA received 17 November 2025. Applicant / manufactured for: Celcuity Inc., 2800 Campus Drive, Suite 140, Minneapolis, MN 55441. Expiry dating (approval letter): 24 months from manufacture at controlled room temperature. The application was not referred to an FDA advisory committee. FDA oncology notice: review used Real-Time Oncology Review (RTOR) and the Assessment Aid.

Labelled indication (USPI §1 / FDA notice): in combination with fulvestrant, with or without palbociclib, for adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected, following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting.

Distinct from covered Veppanu (vepdegestrant): Veppanu is an oral PROTAC labelled for ER+/HER2−, ESR1-mutated advanced breast cancer after endocrine progression. Revtorpyk is an IV pan-PI3K/mTOR agent labelled for PIK3CA-wild-type (no detectable PIK3CA mutation) disease with fulvestrant ± palbociclib. Different biomarker, different molecule, different door — ask the clinic which label fits the molecular report.

PIK3CA-mutant work is not this label: Celcuity company materials (14 Jul 2026) describe a planned Q3 2026 sNDA for a PIK3CA-mutated cohort from VIKTORIA-1 and later filings abroad. That is future / separate regulatory work — not the current US commercial indication.

Where this is taking place

Commercial labelled door today: United States — FDA full approval for the combination line above. A breast / medical oncologist confirms HR+/HER2− status, absence of detectable PIK3CA mutation, prior metastatic endocrine history, baseline fasting glucose / HbA1c, and schedules labelled IV infusions with partner fulvestrant ± oral palbociclib. Prior authorization and plan coverage still apply. Authorized ≠ funded. This is an infusion-centre conversation, not a retail oral pickup.

Patient selection honesty (USPI §2.1): Select patients based on the absence of detected PIK3CA mutations. An FDA-authorized companion diagnostic for PIK3CA mutation status for this indication is not available on the current label. Central trial testing in Study 1 covered a defined mutation panel (including C420R, E542K, E545 variants, Q546E, H1047L/R/Y). Ask the clinic which validated test they use while PMC work on an FDA-authorized CDx continues.

VIKTORIA-1 — NCT05501886 (USPI Study 1) — Phase 3, open-label, randomized, multicenter. Lead sponsor on ClinicalTrials.gov: Celcuity Inc. Status retrieved for this draft: ACTIVE, NOT RECRUITING. Estimated enrolment on the record 701 (programme includes PIK3CA-mutant Study 2 work; the US label efficacy population for Study 1 / PIK3CA-wild-type is 392 adults). Start 8 Dec 2022; estimated primary completion 30 Jun 2026; estimated study completion 31 Dec 2026. Study Director on the CT.gov record: Nadene Zack (Celcuity Inc.). Site countries on the record include Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, India, Italy, Mexico, Poland, Romania, Singapore, South Korea, Spain, Taiwan, the United Kingdom, and the United States. Canadian sites on the record include BC Cancer – Vancouver; Walker Family Cancer Center (St. Catharines); CIUSSS du Saguenay–Lac-Saint-Jean (Chicoutimi); Hospital Notre-Dame and Maisonneuve-Rosemont Hospital (Montreal). Trial geography ≠ a national licence outside the US. Not a new-enrolment door for newly labelled commercial use — Study 1 enrolment that supports the US label is complete; the study continues for follow-up / OS work (PMC 5031-4).

Outside the United States: As of this draft, no confirmed Health Canada Notice of Compliance, European Commission marketing authorisation, MHRA licence, TGA ARTG listing, Swissmedic authorisation, NMPA decision, or PMDA/MHLW licence for Revtorpyk / gedatolisib. Horizon-scan “expected registration” estimates ≠ a licence. Do not import on your own.

The practical door in the US is a breast-oncology clinician who can confirm molecular status (no detectable PIK3CA mutation), prior endocrine / CDK4/6 history, arrange IV chair time, start steroid-containing alcohol-free mouthwash prophylaxis, monitor glucose / rash / mouth sores, and write the labelled partners — not a mail-order bottle from a press headline.

Approval matrix

Access by country

• United States: Ask a breast / medical oncology clinic about FDA-labelled Revtorpyk. Labelled 14 July 2026 for adults with HR+/HER2− locally advanced or metastatic breast cancer without a detectable PIK3CA mutation, after progression on or after ≥1 metastatic endocrine line, in combination with fulvestrant, with or without palbociclib. Dose: 180 mg intravenously over 30 minutes on Days 1, 8, and 15 of every 28-day cycle until progression or unacceptable toxicity. Start steroid-containing alcohol-free mouthwash (4 times daily for the first 8 weeks, longer if needed). Dose reductions: first 150 mg, then 130 mg; permanently discontinue if unable to tolerate 130 mg. No list price or copay dollars in this article. Prior authorization still applies. USPI adverse-reaction contact: Celcuity 1-877-4-CELCUITY (1-877-423-5284); www.celcuity.com; FDA MedWatch 1-800-FDA-1088. Prescribing Information: FDA / DailyMed / Celcuity PI host. This is US commercial labelled IV supply, not Special Access and not a DIY import. Company launch materials also describe a patient-support programme and an expanded-access bridge around commercial availability — ask the treating clinic / Celcuity Medical Information for current eligibility; do not treat EAP as a substitute for labelled commercial supply once the clinic can order the product.

• Canada: Authorisation not confirmed. VIKTORIA-1 lists Canadian sites — that is research geography, not a Product Monograph. Do not assume SAP, named-patient, or cross-border travel for US infusions is available or appropriate. Ask the Canadian breast clinic what legal paths exist in Canada when a Revtorpyk Canadian label does not yet exist.

• European Union / United Kingdom / Australia / Japan / other countries with VIKTORIA-1 sites: Trial participation ≠ commercial Revtorpyk label. Regulator authorisation not confirmed in this draft.

• If your regulator has not authorised it: do not import on your own. Ask the local oncology clinician about documented special-access / named-patient rules or referral to a centre in a labelled country — without treating a US vial as a foreign carton.

Who is eligible (from the US label)

This is an adult, PIK3CA-wild-type (no detectable mutation), post–metastatic endocrine combination conversation on the USPI — not a paediatric label and not a PIK3CA-mutant commercial indication.

United States (USPI / Patient Information, revised / issued July 2026):

• Indication: In combination with fulvestrant, with or without palbociclib, for adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected, following progression on or after at least one line of endocrine therapy in the metastatic setting.
• Dose: 180 mg IV over 30 minutes on Days 1, 8, and 15 of every 28-day cycle until progression or unacceptable toxicity.
• Partners: Read the fulvestrant and (if used) palbociclib labels for their schedules. In Study 1: fulvestrant 500 mg IM Cycle 1 Days 1 and 15, then Day 1 of each cycle; palbociclib 125 mg PO daily Days 1–21 of each 28-day cycle when used.
• Missed infusion: administer as soon as possible; do not wait for the next planned cycle day — reset the 3-on / 1-off timing.
• Stomatitis prophylaxis: steroid-containing alcohol-free mouthwash from start; 4× daily for ≥8 weeks; do not eat/drink for 1 hour after mouthwash.
• Before start: fasting glucose (FPG or FBG), HbA1c; optimize glucose. Achieve optimal glucose control before each infusion. At-home monitoring if HbA1c >6.4%.
• Contraindications: None on the USPI.
• Pregnancy / contraception: Can cause fetal harm. Verify pregnancy status before start when applicable. Females of reproductive potential: effective contraception during treatment and for 2 weeks after the last dose. Males with female partners of reproductive potential: same 2-week window. When used in combination, use the longest contraception window required by any partner product.
• Lactation: Advise not to breastfeed during treatment and for 2 weeks after the last dose (or the longest partner-product window).
• Fertility: May impair fertility in females and males (animal data); findings described as reversible.
• Pediatrics: Safety and effectiveness not established.
• Geriatrics: Of 260 patients who received Revtorpyk, 21% were 65–74 and 6.5% were ≥75; higher Grade ≥3 stomatitis and rash rates in patients ≥65 on both combination arms; no overall effectiveness difference vs younger adults called out.
• Diabetes context: Type 1 or uncontrolled Type 2 diabetes (systemic insulin; HbA1c >6.4%) were excluded from Study 1 — safety in those groups not established.
• Study 1 design context (eligibility narrative on the label — clinic-relevant): prior CDK4/6 inhibitor + non-steroidal aromatase inhibitor; up to two prior endocrine lines for advanced disease; no prior PI3K / AKT / mTOR inhibitor; pre/perimenopausal women required a GnRH agonist.

Not labelled on sources confirmed for this draft:

• PIK3CA-mutated commercial use (company sNDA planned — not today’s USPI indication).
• Children / adolescents.
• EU, UK, Canadian, Japanese, Australian, Swiss, or Chinese Revtorpyk marketing authorisations (not confirmed here).
• Oral / at-home self-administration of gedatolisib.
• Replacing Veppanu (ESR1 PROTAC) or PI3Kα-selective agents by self-switching without a clinician reading both labels.

What the pivotal study showed (VIKTORIA-1 Study 1 / USPI)

Use the USPI for a US prescription conversation. Journals and conference abstracts are supportive reading.

VIKTORIA-1 Study 1 — NCT05501886 (PIK3CA-wild-type cohort):

• Open-label, randomized, multicenter; 392 adults with locally advanced (inoperable) or metastatic HR+/HER2− breast cancer without a detectable PIK3CA mutation.
• Randomized 1:1:1 to Arm A Revtorpyk + fulvestrant + palbociclib (N=131), Arm B Revtorpyk + fulvestrant (N=130), or Arm C fulvestrant alone (N=131).
• Major efficacy outcome: PFS by BICR (RECIST v1.1) for Arm A vs C and Arm B vs C. Additional outcomes: OS, ORR, DoR.
• Baseline (label narrative): median age 56 (28–83); 99% female (26% pre/perimenopausal); 100% Stage IV; all prior endocrine + CDK4/6; 79% visceral metastases; ECOG 0 (59%) or 1 (41%).

USPI Table 6 (efficacy):

At the PFS analysis, OS data were not mature (25% deaths in the overall population). Final OS is a postmarketing commitment (5031-4).

Trial-status honesty: The PIK3CA-wild-type Study 1 analysis supports the US label. CT.gov remains ACTIVE, NOT RECRUITING because follow-up / programme work continues — that is not a door for new commercial starters outside labelled US distribution, and not a licence outside the US. The PIK3CA-mutant cohort is a separate evidence / regulatory track.

How it is taken (US label — keep this exact)

Safety (USPI)

Contraindications: None.

Warnings and precautions:

• Stomatitis (including ulcers / oral mucositis) — Arm A 72% (Grade 3 22%); Arm B 58% (Grade 3 12%). Median onset ~4–7 days. Prophylactic mouthwash required. Withhold / reduce / discontinue by severity.
• Dermatologic adverse reactions (rash) — Arm A 30% (Grade 3 6%); Arm B 40% (Grade 3 5%). Limit sun exposure. Permanently discontinue for SJS/TEN or SJS/TEN-like reactions.
• Hyperglycemia — increased fasting glucose Arm A 46% / Arm B 57% (mostly Grade 1–2; Grade 3 uncommon on the label). Monitor FG and HbA1c; manage with anti-hyperglycemic treatment; withhold / reduce for severe elevations.
• Embryo-fetal toxicity — contraception windows as above.

Most common adverse reactions / lab abnormalities (≥20%):

• With fulvestrant + palbociclib: decreased WBC, neutrophils, hemoglobin, lymphocytes; stomatitis; nausea; decreased platelets; increased fasting glucose; fatigue; vomiting; rash; constipation; diarrhea; increased ALT/AST; musculoskeletal pain; decreased sodium; increased eosinophils.
• With fulvestrant alone: stomatitis; increased fasting glucose; increased eosinophils; decreased hemoglobin; nausea; rash; increased ALT; fatigue; musculoskeletal pain; decreased lymphocytes; vomiting; increased AST; pruritus; diarrhea.

Selected safety (Arm A / Arm B): serious ARs 25% / 19%; permanent discontinuation of Revtorpyk 12% / 9%; dose interruption 64% / 37%; dose reduction 41% / 22%; fatal ARs 2.3% each arm (individual causes ≤0.8% each on the label). Thrombosis appeared among serious events on both gedatolisib arms.

Report suspected adverse reactions to Celcuity 1-877-423-5284 or FDA MedWatch 1-800-FDA-1088.

No boxed warning on the USPI retrieved for this draft. That is not “no risk” — mouth sores, rash, high blood sugar, and pregnancy are the main labelled safety story, with myelosuppression prominent when palbociclib is co-administered.

Research team (source-only)

Names and roles as they appear on primary sources — not a clinic directory.

• Celcuity Inc., Minneapolis, MN — NDA 219908 applicant; USPI “manufactured for”; VIKTORIA-1 sponsor; Patient Information / AE contact 1-877-423-5284 / www.celcuity.com.
• Sunni Miller — Vice President, Regulatory Affairs, Celcuity; addressee on the NDA approval letter (corporate regulatory contact, not a treating clinic).
• R. Angelo de Claro, MD — Director, Office of Oncologic Diseases, OND/CDER — signed the 14 Jul 2026 approval letter.
• Kristie Oh (Kukhwa Oh) — FDA Regulatory Project Manager named on the approval letter (agency contact, not a patient hotline).
• Nadene Zack — Study Director, Celcuity Inc., on the NCT05501886 CT.gov record.
• Sara Hurvitz, MD — Fred Hutchinson Cancer Center / University of Washington; co-principal investigator for VIKTORIA-1 — quoted on the Celcuity 14 Jul 2026 approval press (investigator quote, not a national referral desk).
• Brian Sullivan — CEO and co-founder, Celcuity — quoted on the approval press (company leadership, not a clinic).
• Celcuity Medical Information / AE line: 1-877-4-CELCUITY (1-877-423-5284) — product information and adverse-reaction reporting, not a walk-in infusion desk.

Site-level hospital phone numbers are not listed here — ask your own oncology clinician.

How to talk to a doctor

Bring the brand, the INN, the NCT number, and the US label:

1. “I have HR+/HER2− locally advanced or metastatic breast cancer without a detectable PIK3CA mutation, and I have progressed after at least one metastatic endocrine line. The FDA labelled Revtorpyk (gedatolisib) on 14 July 2026. Is that a fit for me in this country?”
2. “The labelled dose is 180 mg IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle, with fulvestrant ± palbociclib. What infusion-centre logistics and baseline tests (fasting glucose, HbA1c, CBC) do we need?”
3. “VIKTORIA-1 Study 1 (NCT05501886) showed median PFS 9.3 months for the triplet and 7.4 months for the doublet vs 2.0 months for fulvestrant alone. Can we read ORR, DoR, and the immature OS note on the USPI together?”
4. “I do / do not have diabetes, recent mouth sores, severe rash, or prior PI3K / AKT / mTOR therapy. How will we handle mouthwash prophylaxis and glucose monitoring?”
5. “Side effects to watch: mouth sores, rash, high blood sugar, nausea, fatigue, diarrhea, low blood counts (especially with palbociclib). When should I call?”
6. “I understand this is labelled for no detectable PIK3CA mutation — not the planned mutant sNDA, and not the same as oral Veppanu for ESR1 mutations.”
7. If outside the US: “Is there a licence in this country yet? I will not mail-order a US vial or book an infusion as a DIY plan.”
8. “Prior authorization — what does my plan need (HR/HER2 report, PIK3CA-negative result, prior endocrine / CDK4/6 names, staging)?”

Canada zoom: authorisation not confirmed

There is no retrieved Health Canada Notice of Compliance or DIN for Revtorpyk / gedatolisib on the sources used for this draft. US FDA approval does not create a Canadian Product Monograph. VIKTORIA-1 lists Canadian research sites — that is not Canadian marketing authorisation. Do not treat cross-border US infusions as the care plan. Ask a Canadian breast oncologist what legal options exist while waiting for any future Canadian decision.

Bottom line

Revtorpyk (gedatolisib) is an FDA-approved intravenous pan-PI3K / mTOR inhibitor — labelled 14 July 2026 (NDA 219908, novel #25) for adults with HR+/HER2− locally advanced or metastatic breast cancer without a detectable PIK3CA mutation, after ≥1 metastatic endocrine line, in combination with fulvestrant ± palbociclib. Dose is 180 mg IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. VIKTORIA-1 Study 1 (NCT05501886) showed statistically significant PFS gains vs fulvestrant alone (triplet median 9.3 vs 2.0 months, HR 0.24; doublet median 7.4 vs 2.0 months, HR 0.33). Main safety watch: stomatitis, rash, hyperglycemia, and pregnancy, plus myelosuppression when palbociclib is co-used. US primary; other regulators not confirmed. The practical door is a US oncology infusion clinician and a labelled prescription — complementary to, not a substitute for, covered Veppanu for ESR1-mutated disease; a PIK3CA-mutant sNDA is not today’s label; a US vial is not another country’s carton. Authorized is not funded.

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Primary sources

1. FDA — FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer (notice; RTOR, Assessment Aid; Study 1 efficacy numbers; dose 180 mg IV) — https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gedatolisib-fulvestrant-or-without-palbociclib-hr-positive-her2-negative-locally
2. FDA / Celcuity Prescribing Information PDF — REVTORPYK (gedatolisib) for Injection, Revised 7/2026 — https://www.celcuity.com/wp-content/uploads/2026/04/REVTORPYK_PI_2026.pdf (also DailyMed setid 959d73ef-831f-4005-956c-210702270bda)
3. FDA NDA approval letter, NDA 219908, signed R. Angelo de Claro, MD, 14 Jul 2026 — https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/219908Orig1s000ltr.pdf
4. FDA Novel Drug Approvals for 2026 — Revtorpyk / gedatolisib / 7/14/2026 (row 25) — https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026
5. DailyMed — REVTORPYK-gedatolisib injection, powder, for solution — https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=959d73ef-831f-4005-956c-210702270bda
6. Celcuity press release — FDA approval of REVTORPYK (gedatolisib) for HR+/HER2−, PIK3CA wild-type locally advanced or metastatic breast cancer, 14 Jul 2026 — https://ir.celcuity.com/news-releases/news-release-details/celcuity-announces-fda-approval-revtorpyktm-gedatolisib
7. ClinicalTrials.gov VIKTORIA-1 NCT05501886 — https://clinicaltrials.gov/study/NCT05501886