RecruitingPhase 1 / Phase 2

A Study to Evaluate ARV-6723 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Pills, Injections

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "The investigational drug ARV-6723 will be given as an oral tablet on its own and also in combination with other drugs."
  • "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)."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of ARV-6723 and whether it may help fight advanced solid tumors in adults. ARV-6723 is a tablet given alone or with pembrolizumab, another cancer drug. This is the first time ARV-6723 is being tested in people.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • For Parts A1 and A2: Have a solid tumor confirmed by tissue or cell testing that cannot be removed by surgery or has spread.
  • Have had at least one treatment that targets immune checkpoints—signals that control how immune cells fight cancer.
  • Have received standard treatment and have no proven options left, or the study doctor thinks standard treatment is unlikely to help or be tolerated, or have declined standard treatment.
  • Scans must show that the cancer has grown. At least one tumor must be measurable and either never treated with radiation or have grown since radiation.
  • Be fully active or able to do light work. People with greater limits on activity may be considered after discussion with the study's medical monitor.
  • Have organs that work well enough for the study.

Who can't join

  • For Part A: Have active cancer in the brain, or cancer in the lining around the brain and spinal cord.
  • Have a known or suspected allergy to ARV-6723, pembrolizumab, or their ingredients.
  • Have an active autoimmune disease, where the immune system attacks the body, or a past autoimmune disease that may return.
  • Have had severe immune-related side effects from past treatment targeting PD-1, CTLA-4, or LAG-3.
  • Have received a drug that targets a protein called HPK1.
  • Have received cancer drug treatment that acts throughout the body or radiation within 14 days before study treatment starts.
  • Take medicines or herbal supplements that are not allowed in the study and cannot be stopped before and during treatment.
  • Have an abnormal ECG, a test of the heart's electrical activity, that could affect safety or study results.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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.

Study sites (4)

NC

NY

TX

VA