Clinical trial NCT04072952: A Phase 1/2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer
Official title: A Phase 1/2, Open Label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer, Who Have Received Prior Hormonal Therapy and Chemotherapy in the Locally Advanced/Metastatic Setting
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
Metastatic Breast Cancer
Malignant Neoplasm of the Breast
mBC
ER+/HER2-
Locally Advanced Breast Cancer
ARV-471
Vepdegestrant
Palbociclib
Ibrance
Lead sponsor: Arvinas Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2019-08-28
Enrollment: 217
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Subsequent dose level is determined by the Cohort Review Committee after the initial starting dose cohort and each subsequent dose cohort completes the first 28 days of treatment

Dose escalation followed by expansion at a RP2D including a combination cohort with palbociclib (IBRANCE®)
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2 dose escalation and cohort expansion study and will assess the safety, tolerability and anti-tumor activity of ARV-471 alone and in combination with palbociclib (IBRANCE®) in patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) locally advanced or metastatic breast cancer, who have received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.


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 IHC testing and 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.

Primary outcomes:
measure: Part A: Incidence of Dose Limiting Toxicities of ARV-471
timeFrame: 28 Days
measure: Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-471
timeFrame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
measure: Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471
timeFrame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
measure: Part B: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part C: Incidence of Dose Limiting Toxicities of combination ARV-471 + palbociclib
timeFrame: 28 Days
measure: Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of combination ARV-471 + palbociclib
timeFrame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
measure: Part C: Incidence of laboratory abnormalities as a measure of safety and tolerability of combination ARV-471 + palbociclib
timeFrame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Secondary outcomes:
measure: Part A: Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
measure: Part A: Assessment of pharmacokinetic parameter maximum concentration (Cmax).
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
measure: Part A: Assessment of pharmacokinetic parameter minimum concentration (Cmin).
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
measure: Part A: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
measure: Part A: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part A: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part A: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part A: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part A: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part B: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part B: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part B: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part B: Assessment of anti-tumor activity of ARV-471
timeFrame: through study completion, up to approximately 2 years
measure: Part B: Evaluation of Plasma Concentrations of ARV-471
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products]
measure: Part B: Evaluation of Safety and Tolerability
timeFrame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
measure: Part B: Evaluation of Safety and Tolerability
timeFrame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
measure: Part C:Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
measure: Part C: Assessment of pharmacokinetic parameter maximum concentration (Cmax).
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
measure: Part C: Assessment of pharmacokinetic parameter minimum concentration (Cmin).
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
measure: Part C: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)
timeFrame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
measure: Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
timeFrame: through study completion, up to approximately 2 years
measure: Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
timeFrame: through study completion, up to approximately 2 years
measure: Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
timeFrame: through study completion, up to approximately 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Clinical Trial Site
state: California
city: San Francisco
country: United States
facility: Clinical Trial Site
state: California
city: Santa Monica
country: United States
facility: Clinical Trial Site
state: California
city: Norwalk
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Fort Myers
country: United States
facility: Clinical Trial Site
state: Florida
city: Tampa
country: United States
facility: Clinical Trial Site
state: Florida
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Clinical Trial Site
state: Michigan
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: East Brunswick
country: United States
facility: Clinical Trial Site
state: New Jersey
city: Bronx
country: United States
facility: Clinical Trial Site
state: New York
city: Charlotte
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Seattle
country: United States
facility: Clinical Trial Site
state: Washington
Study officials:
References: