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.
Have a histologic or cytologic diagnosis of unresectable or metastatic solid tumor malignancy.
Have previously received at least one prior therapy targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), and/or another T-cell co-stimulatory or immune checkpoint pathway, in any treatment setting (including neoadjuvant or adjuvant).
Have received prior SOC therapy appropriate for their disease type and stage and have no remaining available treatment options with established clinical benefit; or, in the opinion of the investigator, are unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy; or have declined SOC therapy.
Participants must have demonstrated radiographic progression and have at least 1 measurable lesion per RECIST v1.1 that has not been previously irradiated or has demonstrated progression of disease since radiation therapy.
Active brain metastases (new lesions identified on imaging, existing lesions showing progression per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)/imaging characteristics or by clinical criteria, lesions requiring active interventions for symptom control).
Carcinomatous meningitis.
Known or suspected hypersensitivity to ARV-6723 or pembrolizumab or any of its excipients.
Active autoimmune disease or history of autoimmune diseases that may relapse.
Sequential
ARV-6723
DrugOral daily dose of ARV-6723 at an assigned dose.
Pembrolizumab
DrugIV infusion or SQ injection Q3W at an assigned dose.
SOC
DrugInvestigator's choice of SOC drugs.
7
Treatment groupsSee each treatment group below.
Part 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).
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.
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.
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.
Part A1: Area Under the Plasma or Blood Concentration-Time Profile During a Dosing Interval (AUCtau)
Part A1: Area Under the Plasma or Blood Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (Clast) (AUClast)
Part A1: Maximum Plasma or Blood Concentration (Cmax)
Part A1: Lowest Plasma Concentration Immediately Prior to Dosing(Ctrough)
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