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NCT Number: NCT07749586

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

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.

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Key information

Conditions

Advanced Solid Tumor Adenocarcinoma Adnexal Diseases Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Hepatocellular Carcinoma, Merkel Cell Carcinoma, Neuroendocrine Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Carcinoma, Transitional Cell Colonic Diseases Colorectal Neoplasms Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Virus Infections Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Esophageal Diseases Esophageal Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genetic Diseases, Inborn Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Infections Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Male Urogenital Diseases Melanoma Nasopharyngeal Carcinoma Nasopharyngeal Diseases Nasopharyngeal Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuroectodermal Tumors Neuroendocrine Tumors Neuromuscular Diseases Nevi and Melanomas Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Ovarian Diseases Ovarian Neoplasms Peripheral Nervous System Diseases Pharyngeal Diseases Pharyngeal Neoplasms Polyneuropathies Polyomavirus Infections Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Small Cell Lung Carcinoma Stomach Diseases Stomach Neoplasms Stomatognathic Diseases Thoracic Neoplasms Triple Negative Breast Neoplasms Tumor Virus Infections Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Clinical Trial Site, Huntersville, North Carolina, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ARV-6723

Drug

Oral daily dose of ARV-6723 at an assigned dose.

Pembrolizumab

Drug

IV infusion or SQ injection Q3W at an assigned dose.

SoC

Drug

Investigator's choice of SOC drugs.

Primary outcomes

  1. Part A1: Number of Dose-Limiting Toxicities (DLTs) of ARV-6723

    Time frame: 21 days from first ARV-6723 administration

    Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (21 days).

  2. Part A1: Number of Participants With Adverse Events (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)

    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.

  3. Part A2: 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)

    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.

  4. 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

    Time frame: Approximately 24 months

    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.

  5. Part B: ORR by CT/MRI using RECIST v1.1 Criteria Per Investigator Assessment

    Time frame: Approximately 24 months

    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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Part A1: Terminal Elimination Half-Life (t½)

    Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.

  9. 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.

  10. Part A1: Accumulation Ratio (Rac)

    Time frame: At predefined intervals throughout the treatment period, up to approximately 9 months after first dose.

  11. Part A1: Overall Response Rate (ORR)

    Time frame: Approximately 24 months

  12. Part A1: Disease Control Rate (DCR)

    Time frame: Approximately 24 months

  13. Part A2: ORR by CT/MRI using iRECIST Criteria Per Investigator Assessment

    Time frame: Approximately 24 months

  14. Part A2: Disease Control Rate (DCR) by CT/MRI using RECIST 1.1 and iRECIST criteria per investigator assessment

    Time frame: Approximately 24 months

  15. Part B: ORR by CT/MRI Using iRECIST Criteria Per Investigator Assessment

    Time frame: Approximately 24 months

  16. Part B: Progression-Free Survival (PFS)

    Time frame: Approximately 24 months

  17. Part B: Time to Response (TTR)

    Time frame: Approximately 24 months

  18. Part B: Duration of Response (DOR)

    Time frame: Approximately 24 months

  19. Part B: DCR by CT/MRI using RECIST v1.1 and iRECIST Criteria Per Investigator assessment

    Time frame: Approximately 24 months

  20. 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Arvinas Inc.

CONTACT

[email protected]

+1 203 691 1115

Sponsors and collaborators

Lead sponsor

Arvinas Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2031
Study completion
2032
First posted
Aug 6, 2026
Registry last updated
Aug 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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