This is a study to evaluate the safety and potential anti-tumor activity of an investigational drug called ARV-6723, in participants with advanced solid tumors. This is an open-label study which means that participants and study staff will know that all participants will receive ARV-6723. The investigational drug ARV-6723 will be given as an oral tablet on its own and also in combination with other drugs. Researchers think that ARV-6723 can help the body's immune system to better recognize, attack, and destroy cancer cells in adults with advanced solid tumors. ARV-6723 is an investigational drug, and this is the first time ARV-6723 will be used in humans. Depending on the treatment assignment, the investigational drug, ARV-6723, will be given as an oral tablet either on its own (monotherapy) or in combination with pembrolizumab, either through a vein (intravenously or IV) or through an injection beneath the skin (subcutaneously or SQ). This study will include multiple parts: In Part A1 (Phase 1a), different small groups of participants will receive lower to higher doses of ARV-6723 as monotherapy or in combination with standard-dose of pembrolizumab. In Part A2 (Phase 1b), two groups of participants with specific tumor indication(s) (TBD) will receive one of two doses selected based on information from Part A1. Details of Part B will be determined based on information generated from Part A.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
499
Oral daily dose of ARV-6723 at an assigned dose.
IV infusion or SQ injection Q3W at an assigned dose.
Investigator's choice of SOC drugs.
Clinical Trial Site
Huntersville, North Carolina, United States
RECRUITINGClinical Trial Site
San Antonio, Texas, United States
RECRUITINGClinical Trial Site
Fairfax, Virginia, United States
RECRUITINGPart A1: Number of Dose-Limiting Toxicities (DLTs) of ARV-6723
Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (21 days).
Time frame: 21 days from first ARV-6723 administration
Part A1: Number of Participants With Adverse Events (AEs)
AEs as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\]), timing, seriousness, and relationship to study intervention as a measure of safety and tolerability.
Time frame: From the first dose of ARV-6723 through at least 28 days after the last dose (up to approximately 4.7 years)
Part A2: Number of Participants With AEs
AEs as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\]), timing, seriousness, and relationship to study intervention as a measure of safety and tolerability.
Time frame: From the first dose of ARV-6723 through at least 28 days after the last dose (up to approximately 4.7 years)
Part A2: Overall Response Rate (ORR) by computed tomography/magnetic resonance imaging (CT/MRI) Using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) Criteria Per Investigator Assessment
ORR is defined as the proportion of participants reaching a confirmed complete response (CR) or partial response (PR) to the study treatment based on investigator assessment using RECIST 1.1 criteria.
Time frame: Approximately 24 months
Part B: ORR by CT/MRI using RECIST v1.1 Criteria Per Investigator Assessment
ORR is defined as the proportion of participants reaching a confirmed complete response (CR) or partial response (PR) to the study treatment based on investigator assessment using RECIST 1.1 criteria.
Time frame: Approximately 24 months
Part A1: Area Under the Plasma or Blood Concentration-Time Profile During a Dosing Interval (AUCtau)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Area Under the Plasma or Blood Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (Clast) (AUClast)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Maximum Plasma or Blood Concentration (Cmax)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Lowest Plasma Concentration Immediately Prior to Dosing(Ctrough)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Apparent Plasma Clearance at Steady State (CL/F)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Apparent Volume of Distribution Divided by the Bioavailability of the Drug (Vz/F)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Terminal Elimination Half-Life (t½)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Effective Terminal Elimination Half-Life (t½)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
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Part A1: Accumulation Ratio (Rac)
Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.
Part A1: Overall Response Rate (ORR)
Time frame: Approximately 24 months
Part A1: Disease Control Rate (DCR)
Time frame: Approximately 24 months
Part A2: ORR by CT/MRI using iRECIST Criteria Per Investigator Assessment
Time frame: Approximately 24 months
Part A2: Disease Control Rate (DCR) by CT/MRI using RECIST 1.1 and iRECIST criteria per investigator assessment
Time frame: Approximately 24 months
Part B: ORR by CT/MRI Using iRECIST Criteria Per Investigator Assessment
Time frame: Approximately 24 months
Part B: Progression-Free Survival (PFS)
Time frame: Approximately 24 months
Part B: Time to Response (TTR)
Time frame: Approximately 24 months
Part B: Duration of Response (DOR)
Time frame: Approximately 24 months
Part B: DCR by CT/MRI using RECIST v1.1 and iRECIST Criteria Per Investigator assessment
Time frame: Approximately 24 months
Part B: Number of Participants With AEs
Time frame: From the first dose of ARV-6723 through at least 28 days after the last dose (up to approximately 4.7 years)