Recruiting

Phase 1

Phase 2

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

Sponsor:

Arvinas Inc.

Code:

NCT07749586

Conditions

Advanced Solid Tumor

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ARV-6723

Pembrolizumab

SOC

Study Details

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

Study ID

NCT07749586

Start date

Jul 29, 2026

Status verified date

Aug, 2026

Completion date

Mar 31, 2032

Anticipated

Primary completion date

Mar 31, 2031

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

499 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A1a: Phase 1 Monotherapy dose escalation

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.

experimental: Part A1b: Phase 1 Combination therapy dose escalation

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.

experimental: Part A2b: Phase 1 Monotherapy dose optimization

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.

experimental: Part A2b: Phase 1 Combination therapy dose optimization

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.

experimental: Part B: Phase 2 Monotherapy dose expansion

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.

experimental: Part B: Phase 2 Combination dose expansion

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.

experimental: Part B: Phase 2 Standard of care (SOC)

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.

Interventions

ARV-6723

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

Pembrolizumab

IV infusion or SQ injection Q3W at an assigned dose.

SOC

Investigator's choice of SOC drugs.

Primary outcome measure

Part A1: Number of Dose-Limiting Toxicities (DLTs) of ARV-6723 [ Time Frame: 21 days from first ARV-6723 administration ]
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) ]
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) ]
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 ]
Part B: ORR by CT/MRI using RECIST v1.1 Criteria Per Investigator Assessment [ Time Frame: Approximately 24 months ]

Central Contacts and Locations

Central contacts

Arvinas Inc.

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

Locations

Clinical Trial Site

Recruiting

Huntersville, North Carolina, United States, 28078

Clinical Trial Site

Recruiting

San Antonio, Texas, United States, 78229

Clinical Trial Site

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

Arvinas Inc.

Last update posted

Aug 6, 2026

Last verified

Aug, 2026

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)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Arvinas Inc. on 2026-08-06.