A Study to Evaluate ARV-806 in Adults With Advanced Cancer That Has the KRAS G12D Mutation

A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-806 in Participants With KRAS G12D Mutated Advanced Solid Tumors

This is a study to evaluate the safety and potential anti-tumor activity of an investigational agent called ARV-806 in Adults with Advanced Cancer having a specific Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. This is an open-label study which means that participants and study staff will know that all participants will receive ARV-806.

Researchers think that ARV-806 can work by breaking down a specific protein with a mutation that is present in some tumors, which might help prevent or slow tumors from growing. This will be the first time ARV-806 will be used in people. The investigational drug will be given through a vein. This is called intravenous (IV) infusion.

This study will include 2 parts:

In Part A (Phase 1), different small groups of participants will receive lower to higher doses of ARV-806. Adults with advanced cancers having a specific KRAS mutation will be included.

In Part B (Phase 2), participants will be assigned to receive one of up to 2 dose levels decided by the information from Part A. Part B will include participants with advanced pancreatic ductal cancer having a specific KRAS mutation.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Cancer; KRAS G12D Mutation
• Intervention / Treatment: Drug: ARV-806

• Study Type: Interventional
• Enrollment (Estimated): 159
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Clinical Trial Site
    • Phoenix, Arizona, United States, 85004
      • Clinical Trial Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Clinical Trial Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Clinical Trial Site
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Clinical Trial Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Clinical Trial Site
  • New York
    • New York, New York, United States, 10032
      • Clinical Trial Site
    • New York, New York, United States, 10065
      • Clinical Trial Site
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Clinical Trial Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Clinical Trial Site
  • Texas
    • Houston, Texas, United States, 77030-7009
      • Clinical Trial Site
    • San Antonio, Texas, United States, 78229
      • Clinical Trial Site
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Clinical Trial Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Part A:

• Histological or cytological diagnosis of unresectable or metastatic solid tumor malignancy, AND
• Must have evidence of KRAS G12D mutation in tumor tissue or blood (circulating tumor deoxyribonucleic acid [ctDNA]), AND
• Must have received prior standard-of-care (SOC) therapy appropriate for their type and stage of disease and have no other available treatment options with curative intent, or, in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy, AND
• Must have at least 1 measurable lesion

Part B:

• Histological or cytological diagnosis of unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) with KRAS G12D mutation status confirmed by local testing of tumor tissue using a validated molecular or next-generation sequencing (NGS) testing, AND
• Must be willing to provide archival tumor tissue or willing to undergo pretreatment biopsy, AND
• Must have received at least one prior standard of care systemic therapy for PDAC (systemic therapy received in the neoadjuvant or adjuvant setting is allowed), AND
• Participants must have at least 1 measurable lesion

Part A / Part B:

• Eastern Cooperative Oncology Group performance status of 0 or 1,
• Participants with adequate organ function,
• Participants must accept and follow pregnancy prevention guidance.

Exclusion Criteria:

Part A / Part B:

• Active brain metastases
• Carcinomatous meningitis
• Uncontrolled hypertension despite optimal medical therapy
• Prior treatment with a KRAS G12D or a KRAS G12C targeting therapy (pan-KRAS inhibitor/degrader included)
• Participants with an inability to comply with listed prohibited treatments
• Systemic anticancer therapy within 2 weeks or 5 half-lives (whichever is shorter) or radiation therapy (excluding palliative radiation) within 2 weeks prior to the study intervention treatment. If the last immediate anticancer treatment contained an antibody-based agent(s), then an interval of 28 days or 5 half-lives (whichever is shorter) of the agent(s) is required prior to receiving the study intervention treatment.
• Standard 12-lead electrocardiogram that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1/Part A Monotherapy (Dose Escalation); Participants will receive ARV-806 at the assigned doses and regimen (weekly or every 2 weeks).	Drug: ARV-806; Intravenous infusion at assigned dose and dosing schedule
Experimental: Phase 2/Part B Monotherapy (Dose Expansion); Participants will receive ARV-806 at one of up to 2 dose levels/regimens selected from Part A)	Drug: ARV-806; Intravenous infusion at assigned dose and dosing schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B (Phase 2): Overall Response Rate (ORR)	ORR is a parameter measuring the anti-tumor activity of ARV-806. ORR is the percentage of participants for whom the study treatment resulted in a complete response or partial response of the disease under study. It is measured using CT/MRI and RECIST 1.1 criteria per investigator assessment.	Approximately 2 years
Part A (Phase 1): 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 study baseline to at least 28 days after last dose of ARV-806
Part A (Phase 1): Number of dose-limiting toxicities (DLTs) of ARV-806	Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (28 days).	28 days from first ARV-806 administration

Secondary Outcome Measures

Outcome Measure	Time Frame
PK of ARV-806 (Part A): Volume of distribution (Vd)	At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
Part A: Overall Response Rate (ORR)	Approximately 2 years
Part A: Time to Response (TTR)	Approximately 2 years
Part A: Duration of Response (DOR)	Approximately 2 years
Part A: Disease Control Rate (DCR)	Approximately 2 years
Part B: Number of participants with AEs	From the study baseline to at least 28 days after last dose of ARV-806
Part B: Time to Response (TTR)	Approximately 2 years
Part B: Duration of Response (DOR)	Approximately 2 years
Part B: Disease Control Rate (DCR)	Approximately 2 years
Pharmacokinetics (PK) of ARV-806 (Part A): Area under the plasma or blood concentration-time profile during a dosing interval (AUCtau)	At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
PK of ARV-806 (Part A): 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 6 months after first dose of ARV-806
PK of ARV-806 (Part A): Maximum plasma or blood concentration (Cmax)	At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
PK of ARV-806 (Part A): Minimum observed concentration (Cmin)	Timeframe: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
PK of ARV-806 (Part A): Plasma or blood clearance (CL)	At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
PK of ARV-806 (Part A): Time for Cmax (Tmax)	At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
Part B: ARV-806 whole blood pre and post dose concentration	At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

Collaborators and Investigators

• Sponsor: Arvinas Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): April 2, 2029

Study Registration Dates

• First Submitted: June 9, 2025
• First Submitted That Met QC Criteria: June 9, 2025
• First Posted (Actual): June 17, 2025

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; Gastric Cancer; Pancreatic Cancer; Melanoma; Colorectal Cancer; Ovarian Cancer; Advanced Solid Tumors; advanced cancer; Endometrial Cancer; Cholangiocarcinoma; Colon Cancer; KRAS; CRC; Pancreas cancer; Gallbladder Cancer; PDAC; Thyroid Cancer; Esophageal Adenocarcinoma; KRAS G12D Mutation; KRAS G12D Mutated Advanced Solid Tumors; KRAS G12D Mutated Pancreatic Ductal Adenocarcinoma; Appendiceal Carcinoma; Small Bowel Adenocarcinoma; G12D mutation
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Biliary Tract Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Gallbladder Diseases; Thyroid Diseases; Biliary Tract Neoplasms; Skin and Connective Tissue Diseases; Stomach Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; Melanoma; Endometrial Neoplasms; Gallbladder Neoplasms; Thyroid Neoplasms; Adenocarcinoma Of Esophagus
• Other Study ID Numbers: ARV-806-101; 2025-521062-10-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No