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vepdegestrant

Phase 3

Breast Cancer | Small molecule | Oncology |Pfizer, Inc.|Last Updated: May 6, 2026

Target and mechanism

Target class-Estrant (Serd)
ModalitySmall molecule

Also known as PF-07850327, ARV-471, vepdegestrant

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials3
Total Enrollment141

FDA Designations

No designations recorded

Clinical trial landscape

vepdegestrant · 10 trials · 4 indications

Phase 3 1Phase 1 9
NCT05909397Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced Breast CancerBreast Cancer
ACTIVE NOT_RECRUITING59 Analytics
PHASE3ACTIVE NOT_RECRUITING
Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced Breast Cancer
Breast CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Study Lead-in (SLI): Incidence of Grade 4 neutropenia
From randomization date up to Cycle 4 (each cycle is 28 days).

It is defined as the number of participants with Grade 4 neutropenia AE (graded by NCI CTCAE v.5.0) with onset within the first 4 cycles divided by the number of participants.

SLI: Incidence of dose reduction
From randomization date up to Cycle 4 (each cycle is 28 days).

It is defined as the number of participants reducing the dose of palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.

SLI: Incidence of drug discontinuation.
From randomization date up to Cycle 4 (each cycle is 28 days).

It is defined as the number of participants discontinuing palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.

Phase 3: Progression-Free Survival
From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.

Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by Blinded Independent Central Review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or death due to any cause, whichever come first.

Maximum observed concentration (Cmax) for vepdegestrant
Pre-dose, and 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, and 216 hours post dose
Area under the curve from time zero to extrapolated infinite time [AUC (0 - ∞)] for vepdegestrant
Pre-dose, and 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, and 216 hours post dose

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Dose-normalized (dn) Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Vepdegestrant after oral administration
At predefined intervals throughout the treatment period, up to approximately 1 week after the last dose of Vepdegestrant

dn AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) divided by dose. It is obtained from AUC (0 - t) plus AUC (t - ∞).

Dose-normalized (dn) Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Vepdegestrant after IV administration
At predefined intervals throughout the treatment period, up to approximately 1 week after the last dose of Vepdegestrant

dn AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Maximum observed plasma concentration (Cmax) of vepdegestrant when vepdegestrant is administered alone
Period 1 - Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose
Maxium observed plasma concentration of vepdegestrant when vepdegestrant is administered with esomeprazole
Period 2 - Day 5 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose
Area under the curve from time zero to extrapolated infinite time (AUCinf) when vepdegestrant is administered alone
Period 1 - Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

AUCinf=area under the plasama concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0-t) plus AUC (t-inf)

Area under the curve from time zero to extrapolated infinite time (AUCinf) when vepdegestrant is administered with esomeprazole
Period 2 - Day 5 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

AUCinf=area under the plasama concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0-t) plus AUC (t-inf)

Phase 1b: Number of Participants With Dose Limiting Toxicities
28 days

Dose Limiting Toxicities (DLTs) rate for Vepdegestrant in combination with PF-07220060, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).

Phase 2: Percentage of Participants With Objective Response by investigator assessment
Up to approximately 1 year

Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.

Maximum Observed Plasma Concentration (Cmax) of Midazolam when administered alone
Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose
Cmax of Midazolam following multiple doses of Vepdegestrant
Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam when administered alone
Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose
AUCinf of Midazolam following multiple doses of Vepdegestrant
Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose
Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)

Steady-state Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib

Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))

Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471.

Maximum Observed Plasma Concentration (Cmax) of Vepdegestrant when administered alone
Period 1 - Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 144 hour post-dose
Cmax of Vepdegestrant when administered with carbamazepine
Period 2 - Day 14 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 144 hour post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Vepdegestrant when administered alone
Period 1 - Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 144 hour post-dose
AUCinf of Vepdegestrant when administered with carbamazepine
Period 2 - Day 14 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 144 hour post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of ARV-471
Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of ARV-471. AUCinf was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Maximum Observed Plasma Concentration (Cmax) of ARV-471
Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

Cmax was defined as maximum plasma concentration. Cmax of ARV-471 was observed directly from data.

Area Under the Plasma Concentration-Time Profile From Time 0 to 120 Hours (AUC120) of ARV-473
Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose

ARV-473 was the epimer of ARV-471. AUC120 was defined as area under the plasma concentrationtime profile from time zero to 120 hours. AUC120 was calculate by Linear/Log trapezoidal method.

Cmax of ARV-473
Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

ARV-473 was the epimer of ARV-471. Cmax was defined as maximum plasma concentration. Cmax of ARV-473 was observed directly from data.

Number of Participants With Dose Limiting Toxicity (DLTs) During First Treatment Cycle
Cycle 1 (28 days)

DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to ARV-471 and assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.

Secondary Endpoints

SLI and Phase 3. Objective Response Rate
From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).
SLI and Phase 3: Duration of Response
From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).
SLI and Phase 3: Clinical Benefit Rate
Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm A (Investigational Arm)EXPERIMENTALParticipants will receive: * Vepdegestrant, orally, once daily, continuously, in a 28-day cycle, plus * Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment in a 28 day cycle
Arm B (Comparator Arm):ACTIVE_COMPARATORParticipants will receive: * Letrozole, orally, once daily, continuously, in a 28-day cycle, plus * Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment, in a 28-day cycle.
Group 1EXPERIMENTALparticipants with normal hepatic function
Group 2EXPERIMENTALparticipants with moderate hepatic impairment
Group 3EXPERIMENTALparticipants with severe hepatic impairment
Vepdegestrant oral and IV administrationEXPERIMENTALParticipants will receive a single IV infusion of Vepdegestrant on Day 1 of Period 1 followed by a single 200 mg dose of Vepdegestrant registrational tablet on Day 1 of Period 2.
vepdegestrant with or without esomeprazoleEXPERIMENTALvepdegestrant administered as a single dose in Period 1 and Period 2. Esomeprazole administered once a day for 5 days in Period 2
vepdegestrant in combination with PF-07220060EXPERIMENTALvepdegestrant administered orally once daily (QD) continuously and PF-07220060 administered orally twice daily (BID) continuously on 28-day cycles
Midazolam with and without VepdegestrantEXPERIMENTALMidazolam administered as a single dose in Period 1 Day 1, and Period 2 Day 1 and Day 15. Vepdegestrant administered once a day for 15 days in Period 2.
ARV-471 in combination with SamuraciclibEXPERIMENTALARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
Vepdegestrant with and without CarbamazepineEXPERIMENTALVepdegestrant administered as a single dose in Period 1 and Period 2. Carbamazepine administered once a day for 19 days in Period 2.
vepdegestrant with and without itraconazoleEXPERIMENTALvepdegestrant administered as a single dose in Period 1 and Period 2. Itraconazole administered once a day for 11 days in Period 2.
vepdegestrantEXPERIMENTALDaily oral dosages of vepdegestrant

Interventions

NameTypeDescription
Vepdegestrant (ARV-471/PF-07850327)DRUGPharmaceutical form: Tablets. Route of Administration: Oral
PalbociclibCOMBINATION_PRODUCTPharmaceutical form: Capsules. Route of Administration: Oral.
LetrozoleDRUGPharmaceutical form: Capsules. Route of Administration: Orally
vepdegestrantDRUGVepdegestrant administered as a single oral 200 mg dose
Vepdegestrant (Reference)DRUGParticipants will receive a single intravenous (IV) dose of Vepdegestrant on Period 1 Day 1
Vepdegestrant (Test)DRUGParticipants will receive a 200 mg single oral dose of Vepdegestrant tablet formulation on Period 2 Day 1
esomeprazoleDRUGExperimental treatment to assess an endpoint
PF-07220060DRUGDaily oral dosages of PF-07220060 continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days
MidazolamDRUGParticipants will receive a single dose of Midazolam by mouth in Period 1 Day 1, and Period 2 Day 1 and Day 15
SamuraciclibDRUGDaily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
CarbamazepineDRUGParticipants will receive Carbamazepine by mouth once a day for 19 days in Period 2.
ItraconazoleDRUGParticipants will receive itraconazole by mouth once a day for 11 days in Period 2.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites29

Inclusion Criteria: * Adult participants with loco-regional recurrent or metastatic disease not amenable to curative treatment * Confirmed diagnosis of ER+/HER2- breast cancer * No prior systemic treatment for loco-regional recurrent or metastatic disease * Measurable disease evaluable per Response...

Countries:United StatesAustraliaBrazilChinaHungaryItalyJapanSlovakiaSpainSwitzerlandNetherlandsBelgiumCanadaFrancePuerto Rico
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Competitive Landscape -Breast Cancer 402 trials

Top 20 of 92 competitors

CompanyTickerTrialsLead PhaseDrugs
AstraZeneca PLCAZN47PHASE3Fulvestrant, Capivasertib
Merck & Co., Inc.MRK12PHASE3Pembrolizumab, Paclitaxel, Doxorubicin, Epirubicin, Cyclophosphamide
Eli Lilly and CompanyLLY27PHASE3Abemaciclib, Standard Adjuvant Endocrine Therapy
BioNTech SE Sponsored ADRBNTX7PHASE3DB-1303/BNT323, T-DM1
Gilead Sciences, Inc.GILD13PHASE3Sacituzumab Govitecan-hziy, Eribulin, Capecitabine Product, Gemcitabine, Vinorelbine
Novartis AG Sponsored ADRNVS30PHASE3Ribociclib
Pfizer Inc.PFE34PHASE3ARV-471, Fulvestrant
BeOne Medicines Ltd. Sponsored ADRONC5PHASE3BGB-43395, Letrozole, Abemaciclib, Palbociclib, Ribociclib
Olema Pharmaceuticals, Inc.OLMA5PHASE3Palazestrant, Fulvestrant, Anastrozole, Letrozole, Exemestane
Jazz Pharmaceuticals Public Limited CompanyJAZZ3PHASE3Zanidatamab, Trastuzumab, Eribulin, Vinorelbine, Gemcitabine
Celcuity Inc.CELC3PHASE3Gedatolisib, Palbociclib, Fulvestrant, Alpelisib
Relay Therapeutics, Inc.RLAY2PHASE3Zovegalisib, Capivasertib, Fulvestrant
GSK plc Sponsored ADRGSK2PHASE3Niraparib
Greenwich LifeSciences, Inc.GLSI1PHASE3GLSI-100
Bristol-Myers Squibb CompanyBMY5PHASE2Iza-bren, Nab-paclitaxel, Paclitaxel, Capecitabine, Carboplatin
BriaCell Therapeutics CorpBCTX2PHASE3SV-BR-1-GM, Cyclophosphamide, Interferon infiltration of the inoculation site, Retifanlimab, Treatment of Physician's Choice
Incyte CorporationINCY4PHASE2Ruxolitinib, Capecitabine, Regorafenib
Natera, Inc.NTRA3PHASE2Discontinuation of the anti-HER2 maintenance therapy
Puma Biotechnology, Inc.PBYI3PHASE2Neratinib, Loperamide, Colesevelam
Atossa Therapeutics, Inc.ATOS1PHASE2endoxifen, goserelin
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Frequently asked questions about vepdegestrant

What is Vepdegestrant used for?

Vepdegestrant is an investigational small molecule being studied for the treatment of breast cancer, specifically ER+/HER2- locally advanced or metastatic breast cancer. It is also being evaluated in combination with other medicines for advanced or metastatic breast cancer. The drug is currently in clinical development and is not yet approved by the FDA.

What does Vepdegestrant target?

Vepdegestrant is a targeted protein degrader that works by targeting the estrogen receptor (ER). It is classified as a SERD, or selective estrogen receptor degrader, which means it binds to the estrogen receptor and promotes its degradation, thereby reducing estrogen signaling in cancer cells.

Who makes Vepdegestrant?

Vepdegestrant is being developed by Pfizer, Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol PFE. The drug is also known by the development codes ARV-471 and PF-07850327.

What phase is Vepdegestrant in?

Vepdegestrant is in Phase 1 clinical development. While one of its trials, NCT05909397, is listed as a Phase 3 study, the overall development program is primarily in Phase 1. The drug is investigational and has not received FDA approval.

What clinical trials is Vepdegestrant in?

Vepdegestrant is being studied in four clinical trials, including NCT05463952 in Japan for ER+/HER2- breast cancer, NCT05909397 comparing vepdegestrant plus palbociclib to letrozole plus palbociclib in advanced breast cancer, NCT06125522 (TACTIVE-U Sub-Study C) in combination with other medicines, and NCT06206837 with PF-07220060 in advanced or metastatic breast cancer.

Is Vepdegestrant the same as ARV-471?

Yes, Vepdegestrant is the same as ARV-471. It is also known as PF-07850327. These names refer to the same investigational drug being developed by Pfizer for the treatment of breast cancer.