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.
Brief Title
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
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Breast Cancer
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.
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.
Inclusion 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.
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.
Gender
All
Gender Based
false
Keywords
Breast Cancer
Metastatic Breast Cancer
Malignant Neoplasm of the Breast
mBC
ER+/HER2-
Locally Advanced Breast Cancer
ARV-471
Vepdegestrant
Palbociclib
Ibrance
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04072952
Org Class
Industry
Org Full Name
Arvinas Inc.
Org Study Id
ARV-471-mBC-101
Overall Status
Active, not recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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
Outcome Measure
Part A: Incidence of Dose Limiting Toxicities of ARV-471
Outcome Time Frame
28 Days
Outcome Description
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.
Outcome Measure
Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-471
Outcome Time Frame
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Outcome Description
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Outcome Measure
Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471
Outcome Time Frame
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Outcome Description
Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer
Outcome Measure
Part B: Assessment of anti-tumor activity of ARV-471
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Description
First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated
Outcome Measure
Part C: Incidence of Dose Limiting Toxicities of combination ARV-471 + palbociclib
Outcome Time Frame
28 Days
Outcome Description
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination
Outcome Measure
Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of combination ARV-471 + palbociclib
Outcome Time Frame
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Outcome Description
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
Outcome Measure
Part C: Incidence of laboratory abnormalities as a measure of safety and tolerability of combination ARV-471 + palbociclib
Outcome Time Frame
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Secondary Ids
Secondary Id
C4891019
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Outcome Measure
Part A: Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Outcome Description
Maximum concentration (Cmax) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Outcome Measure
Part A: Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Outcome Description
Minimum concentration (Cmin) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Outcome Measure
Part A: Assessment of pharmacokinetic parameter minimum concentration (Cmin).
Outcome Description
Time to maximum concentration (Tmax) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Outcome Measure
Part A: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating overall response rate per RECIST 1.1.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part A: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating clinical benefit response (CBR) rate based on the summation of complete responses (CRs), partial responses (PRs) and stable disease of 24 weeks duration or longer.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part A: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating disease control rate (complete response, partial response, stable disease).
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part A: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating progression free survival.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part A: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating duration of response.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part A: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating overall response rate per RECIST 1.1 in patients with measurable disease at baseline.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part B: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating duration of response.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part B: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating progression-free survival.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part B: Assessment of anti-tumor activity of ARV-471
Outcome Description
Anti-tumor activity of ARV-471 will be assessed by evaluating overall survival.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part B: Assessment of anti-tumor activity of ARV-471
Outcome Description
To characterize the pre-dose concentrations of ARV-471.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products]
Outcome Measure
Part B: Evaluation of Plasma Concentrations of ARV-471
Outcome Description
Further evaluation of safety and tolerability of ARV-471 will be based on adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.
Outcome Time Frame
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Outcome Measure
Part B: Evaluation of Safety and Tolerability
Outcome Description
Further evaluation of safety and tolerability of ARV-471 will be based on Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Outcome Time Frame
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Outcome Measure
Part B: Evaluation of Safety and Tolerability
Outcome Description
Concentration-time curve (AUC) for single and multiple doses of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses, and of palbociclib when given alone and in combination with ARV-471.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Outcome Measure
Part C:Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)
Outcome Description
Maximum concentration (Cmax) for single and multiple doses of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses, and of palbociclib when given alone and in combination with ARV-471
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Outcome Measure
Part C: Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Outcome Description
Minimum concentration (Cmin) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Outcome Measure
Part C: Assessment of pharmacokinetic parameter minimum concentration (Cmin).
Outcome Description
Time to maximum concentration (Tmax) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
Outcome Time Frame
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Outcome Measure
Part C: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)
Outcome Description
Anti-tumor activity of ARV-471 in combination with palbociclib will be assessed by evaluating overall response rate per RECIST 1.1 in patients with measurable disease at baseline.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
Outcome Description
Anti-tumor activity of ARV-471 in combination with palbociclib will be assessed by evaluating clinical benefit response (CBR) rate based on the summation of complete responses (CRs), partial responses (PRs) and stable disease of 24 weeks duration or longer.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
Outcome Description
Anti-tumor activity of ARV-471 in combination with palbociclib will be assessed by evaluating time to event endpoints: progression free survival, duration of response.
Outcome Time Frame
through study completion, up to approximately 2 years
Outcome Measure
Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jesus Anampa Mesias
Investigator Email
janampa@montefiore.org
Investigator Phone
718-920-4826/718-405-8505/646-757-0997
Categories Mesh Debug
Breast Cancer --- BREAST NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Breast Cancer --- BREAST DISEASES
MeSH Terms
BREAST NEOPLASMS
MAMMARY NEOPLASMS, ANIMAL
NEOPLASMS BY SITE
NEOPLASMS
BREAST DISEASES
SKIN DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
ANIMAL DISEASES
PALBOCICLIB