Phase 3, Randomized, Open-Label Study of ARV-471 (PF-07850327) Plus Palbociclib vs Letrozole Plus Palbociclib in Participants With ER(+)/HER2(-) Advanced Breast Cancer (VERITAC-3)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hormonal diseases [C19]

Trial duration

4 Oct 2023 → ongoing

Decision date (initial)

2023-09-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Study Lead-in: To determine the RP3D of palbociclib when given in combination with ARV-471
Phase 3: To demonstrate that ARV-471 in combination with palbociclib is superior to letrozole plus palbociclib in prolonging progression free survival (PFS) in participants with ER(+)/HER2(-) aBC who have not received any prior systematic anticancer therapy for their advanced disease.

Secondary objectives 11

1. Study Lead-in: To evaluate safety and tolerability of both dose levels.
2. Study Lead-in:To evaluate measures of tumor control and duration of response in both dose levels.
3. Study Lead-in:To evaluate the concentrations of ARV-471 and ARV-473.
4. Study Lead-in: To evaluate the concentrations of palbociclib.
5. Phase 3: •To demonstrate that ARV-471 in combination with palbociclib is superior to letrozole in combination with palbociclib, in prolonging overall survival (OS).
6. Phase 3: • To compare measures of tumor control between treatment arms and evaluate duration of response within each treatment arm.
7. Phase 3: •To evaluate safety and tolerability of both treatment arms.
8. Phase 3: • To evaluate the concentrations of ARV-471 and ARV-473
9. Phase 3: •To evaluate the concentrations of palbociclib
10. Phase 3: •To evaluate patient reported outcomes between 2 treatment arms
11. Phase 3: •To assess changes from baseline levels in plasma ctDNA

Conditions and MedDRA coding

ER + /HER 2 - Advanced Breast Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

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. URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening.• Pre-peri menopausal female and male participants must agree on LHRH use. • WOCBP participants and male participants must agree on contraception.
2. Phase 3 ONLY. Participants must provide a blood sample AND a tumor sample collected at the time of diagnosis of locally advanced/metastatic disease. If not available, a de novo biopsy is required. The sole exception is those patients with bone only disease for whom archival tumor sample at initial diagnosis is acceptable.
3. Histological or cytological confirmation of BC with evidence of locoregionally advanced or metastatic disease, not amenable to surgical resection or radiation therapy with curative intent. •Documented ER(+), defined as ER(+) ≥1% stained cells on the most recent tumor biopsy, ie, at diagnosis of recurrence or metastatic disease (Allison et al, 2020). The sole exception is those patients with bone only disease for whom ER(+) using archival tissue at initial diagnosis is acceptable. •Documented HER2(-) tumor by either IHC or in-situ hybridization per ASCO/CAP guideline (Wolff et al, 2018). •Participants who have bilateral BCs which are both ER(+)/HER2(-) are eligible.
4. No prior systemic anti-cancer therapy for their locoregionally advanced or metastatic disease.
5. At least 1 measurable lesion as defined by RECIST v1.1. Bone only disease: participants with only non-measurable lesions are eligible.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.

Exclusion criteria 5

1. Prior treatments: •Primary endocrine resistance: relapse while on the first 2 years of standard adjuvant ET. •Secondary endocrine resistance: -relapse while on standard adjuvant ET but after the first 2 years -relapse within 12 months of completing standard adjuvant ET •CDK4/6i, ARV-471, fulvestrant, elacestrant and other investigational agents (including novel ET, any SERDs, SERCAs, CERANs) in any setting. •Participation in other studies involving investigational drug(s) within 28 days prior to randomization. If in the FU Phase, the participant is eligible provided at least 5 half-lives have elapsed from the last dose.
2. Concurrent administration of medications, food or herbal supplements that are strong inhibitors or strong inducers of CYP3A. Prior use of strong CYP3A inhibitors must be stopped 7 days before randomization and strong CYP3A inducers must be stopped 14 days before randomization.
3. Lack of adequate bone marrow, liver and kidney function.
4. Impaired cardiovascular function or clinically significant cardiovascular diseases.
5. Refractory nausea and vomiting, chronic GI disease, GI ulcer, GI bleeding, inability to swallow the formulated product or previous significant gastric (total or partial), bowel resection that would preclude adequate absorption of study interventions.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Study Lead-in: •Incidence of Grade 4 neutropenia AE (as graded by NCI CTCAE v5.0) with onset within the first 4 cycles. •Incidence of dose reduction or drug discontinuation within the first 4 cycles.
2. Phase 3: •Progression-free survival (PFS), defined as the time from the date of randomization to the date of first documented disease progression, as determined by BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first.

Secondary endpoints 11

1. Study Lead-in: •Incidence of AEs and SAEs •Incidence of laboratory abnormalities. •Incidence of ECG abnormalities.
2. Study Lead-in: •Objective Response, Clinical Benefit Response, Duration of response as determined by investigator assessment per RECIST v1.1
3. Study Lead-in: •Plasma concentrations of ARV-471 and ARV-473.
4. Study Lead-in: •Plasma concentrations of palbociclib.
5. Phase 3: •Overall Survival (OS), defined as the time from the date of randomization to the date of death due to any cause.
6. Phase 3: •Objective Response, clinical Benefit Response, duration of response as determined by BICR assessment per RECIST v 1.1
7. Phase 3: •Incidence of AEs and SAEs • Incidence of laboratory abnormalities. •Incidence of ECG abnormalities.
8. Phase 3: •Plasma concentrations of ARV-471 and its epimer ARV-473.
9. Phase 3: •Plasma concentrations of palbociclib.
10. Phase 3: • EuroQol EQ-5D-5L •EORTC QLQ-C30 •EORTC QLQ-BR23
11. Phase 3: •ctDNA plasma quantitative changes from pretreatment to evaluate potential predictability of their associations with clinical outcomes.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

235 East 42nd Street

City

New York

Postcode

10017-5703

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 2

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 63 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications