TACTIVE-U: A Study to Learn About the Study Medicine (Called ARV-471) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)

Breast Cancer, Cancer

Phase 2

Interventional Study

TACTIVE-U: A Study to Learn About the Study Medicine (Called ARV-471) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)

Sponsor

Pfizer

Start Date

01/03/2023

Completion Date

06/04/2026

Sex

ALL

Enrollment

Ages From

Healthy Volunteers?

Yes

Contact

Pfizer CT.gov Call Center

Location

Siteman Cancer Center - WUPI

Trial Details

Brief Summary

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer. This study is seeking participants who have breast cancer that: is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy is sensitive to hormonal therapy (it is called estrogen receptor positive); and is no longer responding to previous treatments This study is divided into separate sub-studies. For Sub-Study B: All participants will receive ARV-471 and a medicine called ribociclib. ARV-471 and ribociclib will be given at the same time by mouth, at home, 1 time a day. The experiences of people receiving the study medicine will be examined. This will help determine if the study medicine is safe and effective. Participants will continue to take ARV-471 and ribociclib until their cancer is no longer responding, or side effects become too severe. They will have visits at the study clinic about every 4 weeks.

Official Title

TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF ARV-471 (PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 YEARS AND OVER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY B (ARV-471 IN COMBINATION WITH RIBOCICLIB)

Detailed Description

C4891023 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with ribociclib in the treatment of participants with A/MBC. The sub-study is part of Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer. ARV-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in ER+ breast cancer.

Selection Criteria

Eligibility Inclusion Criteria

histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy).
prior anticancer therapies: up to 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, metastatic)
at least 1 measurable lesion as defined by RECIST v1.1.
ECOG PS ≤1.

Eligibility Exclusion Criteria

visceral crisis at risk of life-threatening complications in the short term
known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
newly diagnosed brain metastases, or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 14 days prior to enrollment in the of study.
history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix.
inflammatory breast cancer
impaired cardiovascular function or clinically significant cardiovascular diseases
concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of CYP3A and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
renal impairment, not adequate liver function and/or bone marrow function
known active infection

ARMS & Interventions

PARTICIPANT GROUP ARM	INTERVENTION TREATMENT
Experimental: ARV-471 in combination with Ribociclib ARV-471 administered orally QD continuously and Ribociclib administered orally QD consecutively for 21 days followed by 7 days off treatment on 28-day cycles	Drug: ARV-471 Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days Drug: Ribociclib Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days

Primary Outcome

Measures	Measure Description	MEASURE TIME FRAME
Phase 1b: Number of Participants With Dose Limiting Toxicities	Dose Limiting Toxicities rate for ARV-471 in combination with Ribociclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 [28 days]).	28 days
Phase 2: Percentage of Participants With Objective Response by investigator assessment	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.	Up to approximately 1 year

Secondary Outcome

MEASURES	MEASURE DESCRIPTION	MEASURE TIME FRAME
Phase 1b: Percentage of Participants With Objective Response by investigator assessment	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.	Up to approximately 1 year
Phase 1b: Evaluation of effect of ribociclib on PK of ARV-471	AUCtau and Cmax of ARV-471 with and without co-administration of ribociclib	At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
Phase 1b and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Ribociclib	AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to ARV-471 in combination with ribociclib. Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing.	First study drug dose through a minimum of 28 Days After Last study drug administration
Phase 1b and Phase 2: Duration of Response by investigator assessment.	Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.	Up to approximately 1 year
Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.	Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) ≥24 weeks	Up to approximately 1 year
Phase 1b and Phase 2: Progression Free Survival by investigator assessment.	Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs firs	Up to approximately 1 year
Phase 1b and Phase 2: Plasma concentrations of ARV-471 and ribociclib.	To evaluate the plasma exposure of ARV-471 and ribociclib when ARV-471 and ribociclib are given in combination.	At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
Phase 2: Overall Survival	Overall Survival (OS) is defined as the time from the date of first dose of study interventions to the date of death due to any cause	Through study completion, up to approximately 3 year
Phase 2:ctDNA plasma quantitative changes from pre-treatment	To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes.	At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment

Other Outcome

MEASURES	MEASURE DESCRIPTION	MEASURE TIME FRAME

Breast Cancer, Cancer

Phase 2

Interventional Study