A Phase 1/2 Trial of ARV-471 Alone and in Combination Wit... | NCT04072952

ID	Type	Description	Link
C4891019	Other Identifier	Pfizer

Status Module

Name	Class
Pfizer	INDUSTRY

Label	Type	Description	Intervention Names
ARV-471	Experimental	Parts A and B: ARV-471 administered once daily (QD) or twice daily (BID) for 28 day cycles.	Drug: ARV-471
ARV-471 and palbociclib (IBRANCE®)	Experimental	Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days.	Drug: ARV-471 in combination with palbociclib (IBRANCE®)

Name	Type	Description	Arm Group Labels	Other Names
ARV-471	Drug	Parts A and B: ARV-471 administered QD or BID for 28 day cycles.	ARV-471

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part A: Incidence of Dose Limiting Toxicities of ARV-471	First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug	28 Days
Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-471	Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.	First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.	First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Part B: Assessment of anti-tumor activity of ARV-471	Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer	through study completion, up to approximately 2 years
Part C: Incidence of Dose Limiting Toxicities of combination ARV-471 + palbociclib	First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated	28 Days
Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of combination ARV-471 + palbociclib

Secondary Outcomes

Measure	Description	Time Frame
Part A: Assessment of pharmacokinetic (PK) parameter area under the concentration-time curve (AUC).	Concentration-time curve (AUC) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.	At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Part A, Part B, and Part C:

Patients at least 18 years of age at the time of signing the informed consent.
Patients must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer for which standard curative therapy is no longer effective or does not exist.
Patients must have measurable or non-measurable disease by RECIST criteria (version1.1), with radiologic tumor assessments performed within 28 days of the first dose of therapy.
Patients must be willing to undergo a core biopsy of accessible tumor within 4 weeks prior to the initiation of study treatment and a follow-up biopsy on treatment for ER immunohistochemistry (IHC) testing and pharmacodynamics (PD) studies. (Patients without accessible tumor tissue may be eligible after discussion with the Medical Monitor.)
Women must be postmenopausal due to surgical or natural menopause.

Part A:

- Patients must have received at least 2 prior endocrine regimens in any setting (neoadjuvant, adjuvant or advanced/metastatic) a CDK4/6 inhibitor and up to 3 prior regimens of cytotoxic chemotherapy in the locally advanced or metastatic setting.

Part B:

Patients must have received at least 1 prior endocrine regimen for a minimum of 6 months in the locally advanced or metastatic setting; if more than 1 prior endocrine regimen has been administered, only one of the regimens must have been administered for a minimum of 6 months in the locally advanced or metastatic setting
Patients must have received a CDK4/6 inhibitor
Patients must have received up to 1 prior regimen of cytotoxic chemotherapy in the locally advanced or metastatic setting
Women must be postmenopausal due to surgical or natural menopause.

Part C:

Patients must have received at least one prior endocrine regimen.
Patients must have received no more than two prior chemotherapy regimens for advanced disease.
Women must be postmenopausal due to surgical or natural menopause.

Exclusion Criteria:

Part A, Part B, and Part C:

Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses). Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to first dose of study drug, have discontinued high-dose corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable as judged by the Investigator.
Receipt of prior anti-cancer or other investigational therapy within 14 days prior to the first administration of study drug.
Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study.

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Trial Site		Palo Alto	California	94304	United States
Clinical Trial Site

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases