A Phase 1/2 Open-label Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of ARV-6723 Administered as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

Study Identifier:
ARV-6723-101
CT.gov Identifier:
NCT07749586
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2026-525614-57-00
Study Contact Information:
N/A
Recruiting

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Study Summary

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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
N/A
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: EXPERIMENTAL: Part A1a: Phase 1 Monotherapy dose escalation
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Drug: Participants will receive the assigned dose of ARV-6723 orally once daily (QD) in tablet form, under fasted conditions in 21-day cycles. Treatment will continue at the investigator's discretion until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Drug: ARV-6723
Drug: Oral daily dose of ARV-6723 at an assigned dose.
Drug: EXPERIMENTAL: Part A1b: Phase 1 Combination therapy dose escalation
Drug: Participants will receive the assigned dose of ARV-6723 orally QD in tablet form, under fasted conditions along with pembrolizumab by intravenous (IV) infusion or subcutaneous (SQ) injection at fixed dose once every 3 weeks (Q3W) in 21-day cycles. Treatment will continue at the investigator's discretion until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Drug: Pembrolizumab
Drug: IV infusion or SQ injection Q3W at an assigned dose.
Drug: EXPERIMENTAL: Part A2b: Phase 1 Combination therapy dose optimization
Drug: Participants will receive the assigned dose of ARV-6723, based on Phase A1b orally QD in tablet form, under fasted conditions along with pembrolizumab IV infusion or SQ injection at fixed dose Q3W in 21-day cycles. Treatment will continue at the investigator's discretion until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: EXPERIMENTAL: Part A2b: Phase 1 Monotherapy dose optimization
Drug: Participants will receive the assigned dose of ARV-6723, based on Phase A1a, orally QD in tablet form, under fasted conditions in 21-day cycles. Treatment will continue at the investigator's discretion until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: EXPERIMENTAL: Part B: Phase 2 Combination dose expansion
Drug: Participants will receive the assigned dose of ARV-6723, selected based on Part A in combination with pembrolizumab by IV infusion or SQ injection n 21-day cycles. Treatment will continue at the investigator's discretion until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: EXPERIMENTAL: Part B: Phase 2 Monotherapy dose expansion
Drug: Participants will receive the assigned dose of ARV-6723, selected based on Part A in 21-day cycles. Treatment will continue at the investigator's discretion until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: EXPERIMENTAL: Part B: Phase 2 Standard of care (SOC)
Drug: Participants will receive SOC treatment regimens based on investigators choice and the tumor indications. Treatment will continue at the investigator's discretion until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Drug: SOC
Drug: Investigator's choice of SOC drugs.
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Part A1 dose escalation and A2 dose optimization: Participants must meet all of the following criteria:
  • * 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.
  • * ECOG PS 0 or 1 or equivalent. Participants with ECOG PS 2 may be considered upon discussion with the Sponsor Medical Monitor.
  • * Participants with adequate organ function.
Exclusion criteria
  • Exclusion Criteria (Part A)
  • * 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.
  • * History of severe immune-related adverse events (irAE) attributed to prior anti-PD-1/anti-CTLA-4/anti-LAG-3 therapy.
  • * Prior treatment with any HPK1-targeting agent
  • * Systemic anti-cancer therapy or radiation therapy within 14 days prior to study treatment start.
  • * Current use of any prohibited concomitant medication(s) or herbal supplements which cannot be discontinued, prior to start of study intervention and for the duration of the study.
  • * Baseline (screening) standard 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Amita Patnaik
Status
Recruiting
Condition(s) Treated at Site