Neoplasms

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Breast Neoplasms

Breast Diseases

Skin Diseases

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Letrozole

Estrogens

Mitogens

Palbociclib

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

Participants will receive:

* ARV-471, 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

Participants 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.

Pharmaceutical form: Tablets. Route of Administration: Oral

ARV-471 (PF-07850327)

Pharmaceutical form: Capsules. Route of Administration: Oral.

Pharmaceutical form: Capsules. Route of Administration: Orally

Pfizer CT.gov Call Center

The purpose of this study is to understand the safety and effects of the study medicine ARV-471 (PF-07850327) given together with palbociclib in advanced breast cancer. In particular, the study will compare the combination of ARV-471 plus palbociclib to standard of care therapy (letrozole plus palbociclib). Both letrozole and palbociclib are medicines already used for treatment of breast cancer. ARV-471 is a new medicine under study.

This study is seeking participants who have breast cancer that:

* Have a locally advanced or metastatic disease and cannot be fully cured by surgery or radiation therapy. A metastatic disease is when disease has spread to other parts of the body.
* Is sensitive to hormonal therapy such as tamoxifen. This is called estrogen receptor positive disease.
* Have not received any prior medicine for advanced disease. Example medications include tamoxifen or letrozole or exemestane.

The study will have an open-label SLI (study lead-in) before initiation of Phase 3 trial. During SLI, two dose levels of palbociclib in combination with ARV-471 will be explored in parallel. Assignment to the palbociclib dose is by chance. Half of the participant will receive one dose and the other half another palbociclib dose. The purpose of SLI is to determine the recommended Phase 3 dose of palbociclib to be administered in combination with ARV-471.

In the Phase 3, half of the participants will take ARV-471 plus palbociclib while the other half will take letrozole plus palbociclib. In both SLI and Phase 3, participants will take the study medicines by mouth, with food, once a day. Participants will take the study medicines until breast cancer increase in size or side effects become too severe. Side effects refer to unwanted reactions to medications. Participants will visit the study clinic about once every 4 weeks.

The purpose of this study is to demonstrate that ARV-471 in combination with palbociclib provides superior clinical benefit compared to letrozole in combination with palbociclib in participants with ER(+)/HER2(-) aBC who have not received any prior systemic anti-cancer therapies for their locoregionally advanced or metastatic disease. The study will have a Study Lead-in (SLI) and a Phase 3. In the SLI, 50 participants (approximately 25 each arm) will be randomly assigned on a 1:1 basis to one of the two dose levels (DLs). In the randomized Phase 3, approximately 1130 eligible participants (approximately 565 each arm) will be randomized in a 1:1 ratio to the Experimental Arm (ie, ARV-471 plus palbociclib at RP3D determined in the SLI) or Control Arm (ie, letrozole plus palbociclib at the registered doses). Randomization will be stratified by menopausal status at study entry, visceral disease and de novo metastatic disease.

A Study of ARV-471 (PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer

A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY OF ARV-471(PF-07850327) PLUS PALBOCICLIB VERSUS LETROZOLE PLUS PALBOCICLIB FOR THE TREATMENT OF PARTICIPANTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI-CANCER TREATMENT FOR ADVANCED DISEASE (VERITAC-3)

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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.

It is defined as the number of participants reducing the dose of palbociclib and/or ARV-471 due to any cause occurring within the first 4 cycles divided by the number of participants.

It is defined as the number of participants discontinuing palbociclib and/or ARV-471 due to any cause occurring within the first 4 cycles divided by the number of participants.

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.

Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as best overall response determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1, from the date of randomization to the date of disease progression or death due to any cause, whichever occurs first.

Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1 or death due to any cause, whichever occurs first.

Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR at any time or SD or non CR/non PD for at least 24 weeks determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1, from the date of randomization until disease progression or death due to any cause, whichever occurs first.

Overall survival is defined as the time interval from the date of randomization to the date of documented death, due to any cause.

It is defined as the number of participants with TEAEs and SAEs divided by the number of participants. AEs and SAEs will be graded according to NCI CTCAE V5.0.

It is defined as the number of participants with laboratory abnormalities divided by the number of participants. Laboratory abnormalities will be graded according to NCI CTCAE V5.0.

It is defined as the number of participants with ECG abnormalities divided by the number of participants. ECG abnormalities will be graded according to NCI CTCAE V5.0.

Plasma concentrations of ARV-471 and palbociclib

Change from baseline between treatment comparison in Quality of Life using the EQ-5D 5L questionnaire.

Change from baseline between treatment comparison in Quality of Life using the EORTC QLQ-C30 questionnaire.

Change from baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) questionnaire.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of ARV-471 (PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer	NCT05909397	Breast Cancer	ARV-471 (PF-078... Palbociclib Letrozole Palbociclib	18 Years -	Pfizer
A Study of ARV-471 (PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer	NCT05909397	Breast Cancer	ARV-471 (PF-078... Palbociclib Letrozole Palbociclib	18 Years -	Pfizer

Spots Global Cancer Trial Database for advanced cancer of the breast