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

NCT07749586 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ARV-6723-1012026-525614-57-00
• Study Type: interventional
• Target: 499
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

Advanced solid tumors; PROTAC; HPK1; MAP4K1; Immune checkpoint inhibitor; Non-small cell lung cancer (NSCLC); Renal cell carcinoma (RCC); Melanoma; Gastric cancer; Gastroesophageal cancer; Esophageal cancer; Head and Neck Squamous cell carcinoma (HSNCC); Urothelial carcinoma (UC); Colorectal Cancer (CRC); Triple-negative breast cancer (TNBC); Ovarian cancer; Cervical cancer; Merkel cell carcinoma; Skin squamous cell carcinoma (SCC); Nasopharyngeal carcinoma; Small cell lung cancer (SCLC); Hepatocellular carcinoma (HCC)

Outcome Measures

Primary Outcomes (5)

• 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).

  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.

  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.

  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.

  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.

  Approximately 24 months

Secondary Outcomes (20)

• Part A1: Area Under the Plasma or Blood Concentration-Time Profile During a Dosing Interval (AUCtau)

  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)

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

• Part A1: Maximum Plasma or Blood Concentration (Cmax)

  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)

  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)

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

Study Arms (7)

Part A1a: Phase 1 Monotherapy dose escalation

EXPERIMENTAL

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: ARV-6723

Part A1b: Phase 1 Combination therapy dose escalation

EXPERIMENTAL

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: ARV-6723; Drug: Pembrolizumab

Part A2b: Phase 1 Monotherapy dose optimization

EXPERIMENTAL

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: ARV-6723

Part A2b: Phase 1 Combination therapy dose optimization

EXPERIMENTAL

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: ARV-6723; Drug: Pembrolizumab

Part B: Phase 2 Monotherapy dose expansion

EXPERIMENTAL

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: ARV-6723

Part B: Phase 2 Combination dose expansion

EXPERIMENTAL

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: ARV-6723; Drug: Pembrolizumab

Part B: Phase 2 Standard of care (SOC)

EXPERIMENTAL

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: SOC

Interventions

ARV-6723 DRUG

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

Part A1a: Phase 1 Monotherapy dose escalation; Part A1b: Phase 1 Combination therapy dose escalation; Part A2b: Phase 1 Combination therapy dose optimization; Part A2b: Phase 1 Monotherapy dose optimization; Part B: Phase 2 Combination dose expansion; Part B: Phase 2 Monotherapy dose expansion

Pembrolizumab DRUG

IV infusion or SQ injection Q3W at an assigned dose.

Part A1b: Phase 1 Combination therapy dose escalation; Part A2b: Phase 1 Combination therapy dose optimization; Part B: Phase 2 Combination dose expansion

SOC DRUG

Investigator's choice of SOC drugs.

Part B: Phase 2 Standard of care (SOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arvinas Inc.: lead

Study Sites (3)

Clinical Trial Site

Huntersville, North Carolina, 28078, United States

RECRUITING

Clinical Trial Site

San Antonio, Texas, 78229, United States

RECRUITING

Clinical Trial Site

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Melanoma; Stomach Neoplasms; Esophageal Neoplasms; Carcinoma, Transitional Cell; Colorectal Neoplasms; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Carcinoma, Merkel Cell; Nasopharyngeal Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Hepatocellular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Arvinas Inc.

CONTACT

+1 203 691 1115; ARV-6723-101-ClinicalContacts@arvinas.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2026
• First Posted: August 6, 2026
• Study Start: July 29, 2026
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): March 31, 2032
• Last Updated: August 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)