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Active, Not Recruiting

NCT Number: NCT07023731

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

KRAS G12D Mutation Adenocarcinoma Adenocarcinoma Of Esophagus Adnexal Diseases Advanced Solid Cancer Biliary Tract Diseases Biliary Tract Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Cholangiocarcinoma Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gallbladder Diseases Gallbladder Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Ovarian Diseases Ovarian Neoplasms Pancreatic Diseases Pancreatic Neoplasms Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Stomach Diseases Stomach Neoplasms Thoracic Neoplasms Thyroid Diseases Thyroid Neoplasms Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Clinical Trial Site, Phoenix, Arizona, 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 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

Treatment and study plan

ARV-806

Drug

Intravenous infusion at assigned dose and dosing schedule

Primary outcomes

  1. Part A (Phase 1): Number of dose-limiting toxicities (DLTs) of ARV-806

    Time frame: 28 days from first ARV-806 administration

    Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (28 days).

  2. Part A (Phase 1): Number of participants with AEs

    Time frame: From the study baseline to at least 28 days after last dose of ARV-806

    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 B (Phase 2): Overall Response Rate (ORR)

    Time frame: Approximately 2 years

    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.

Secondary outcomes

  1. Pharmacokinetics (PK) of ARV-806 (Part A): 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 6 months after first dose of ARV-806

  2. 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)

    Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

  3. PK of ARV-806 (Part A): Maximum plasma or blood concentration (Cmax)

    Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

  4. PK of ARV-806 (Part A): Minimum observed concentration (Cmin)

    Time frame: Timeframe: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

  5. PK of ARV-806 (Part A): Plasma or blood clearance (CL)

    Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

  6. PK of ARV-806 (Part A): Time for Cmax (Tmax)

    Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

  7. PK of ARV-806 (Part A): Volume of distribution (Vd)

    Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

  8. Part A: Overall Response Rate (ORR)

    Time frame: Approximately 2 years

  9. Part A: Time to Response (TTR)

    Time frame: Approximately 2 years

  10. Part A: Duration of Response (DOR)

    Time frame: Approximately 2 years

  11. Part A: Disease Control Rate (DCR)

    Time frame: Approximately 2 years

  12. Part B: Number of participants with AEs

    Time frame: From the study baseline to at least 28 days after last dose of ARV-806

  13. Part B: ARV-806 whole blood pre and post dose concentration

    Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806

  14. Part B: Time to Response (TTR)

    Time frame: Approximately 2 years

  15. Part B: Duration of Response (DOR)

    Time frame: Approximately 2 years

  16. Part B: Disease Control Rate (DCR)

    Time frame: Approximately 2 years

Sponsors and collaborators

Lead sponsor

Arvinas Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2029
First posted
Jun 17, 2025
Registry last updated
Jul 2, 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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