The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Vepdegestrant is an investigational compound. Its safety and efficacy have not been established. * Vepdegestrant is being co-developed with Arvinas.
Active enrolling
United States, Belgium, Canada, France, Italy, Puerto Rico, Spain
EXPERIMENTAL: ARV-471 in combination with Samuraciclib
ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
DRUG: vepdegestrant
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 daysDRUG: Samuraciclib
Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 daysPhase 1b: Number of Participants With Dose Limiting Toxicities
Dose Limiting Toxicities rate for ARV-471 in combination with Samuraciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).
28 days
Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
Steady-state Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
Steady-state Peak Plasma concentration ( Cmax) of ARV-471 with and without coadministration of samuraciclib
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 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
Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471.
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
Single dose Cmax of samuraciclib with and without coadministration of ARV 471.
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib
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 samuraciclib. Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing. Changes from baseline for the ECG parameters heart rate, QTcF, PR interval, and QRS complex will be summarized by treatment and time. The frequency of uncorrected QT values above 500 ms will be tabulated.
First study drug dose through a minimum of 28 Days After Last study drug administration
Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib
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 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 first.
Up to approximately 1 year
Phase 1b and Phase 2: Plasma concentrations of ARV-471 and samuraciclib.
To evaluate the plasma exposure of ARV-471 and samuraciclib when ARV-471 and samuraciclib are given in combination.
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
AUCtau of ARV-471 with and without co-administration of samuraciclib
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
Cmax of ARV-471 with and without co-administration of samuraciclib
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
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
Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity
Participants classified on basis of pathological TP53 mutation detected or not detected.
Screening
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
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Sponsor: Pfizer
Collaborator: Arvinas Estrogen Receptor, Inc., Carrick Therapeutics Limited
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT06125522
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