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

NCT07749586
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
499
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Lead sponsor
Arvinas Inc.
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Start date
2026-07-29
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Number of sites
3
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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.
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Short title
A Study to Evaluate ARV-6723 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors
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Official 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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2032-03-31
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First posted
2026-08-06
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Registry last updated
2026-08-06
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Primary completion date
2031-03-31
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Start date
2026-07-29
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Participants
499
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Participant count basis
Estimated
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Planned participants
499
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Protocol amendments
0
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Number of sites
3
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Arvinas Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07749586
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ClinicalTrials.gov ID
NCT07749586
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Registry record
Open registry record
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Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

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

    Timeframe: 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)

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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.

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

    Timeframe: 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)

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

  3. Part A1: Maximum Plasma or Blood Concentration (Cmax)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

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

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

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

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

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

  10. Part A1: Accumulation Ratio (Rac)

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

  11. Part A1: Overall Response Rate (ORR)

    Timeframe: Approximately 24 months

  12. Part A1: Disease Control Rate (DCR)

    Timeframe: Approximately 24 months

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

    Timeframe: Approximately 24 months

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

    Timeframe: Approximately 24 months

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

    Timeframe: Approximately 24 months

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

    Timeframe: Approximately 24 months

  17. Part B: Time to Response (TTR)

    Timeframe: Approximately 24 months

  18. Part B: Duration of Response (DOR)

    Timeframe: Approximately 24 months

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

    Timeframe: Approximately 24 months

  20. Part B: Number of Participants With AEs

    Timeframe: From the first dose of ARV-6723 through at least 28 days after the last dose (up to approximately 4.7 years)

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

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 (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.
Sources for eligibility
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  • Clinical Trial SiteHuntersville, United StatesRecruiting
  • Clinical Trial SiteSan Antonio, United StatesRecruiting
  • Clinical Trial SiteFairfax, United StatesRecruiting
Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2026-525614-57-00
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (14)

Targets (1)