NCT07023731

Brief Summary

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 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
159

participants targeted

Target at P75+ for phase_1

Timeline
36mo left

Started May 2025

Longer than P75 for phase_1

Geographic Reach
1 country

14 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress24%
May 2025Apr 2029

Study Start

First participant enrolled

May 29, 2025

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

June 9, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

June 17, 2025

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2027

Expected
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 2, 2029

Last Updated

February 19, 2026

Status Verified

February 1, 2026

Enrollment Period

2.5 years

First QC Date

June 9, 2025

Last Update Submit

February 17, 2026

Conditions

Keywords

KRAS G12D MutationAdvanced Solid TumorsKRAS G12D Mutated Advanced Solid TumorsKRAS G12D Mutated Pancreatic Ductal AdenocarcinomaPancreatic CancerPDACNon-Small Cell Lung CancerNSCLCColorectal CancerColon CancerCRCAppendiceal CarcinomaCholangiocarcinomaEndometrial CancerEsophageal AdenocarcinomaGallbladder CancerGastric CancerMelanomaOvarian CancerSmall Bowel AdenocarcinomaThyroid Canceradvanced cancerKRASG12D mutationPancreas cancer

Outcome Measures

Primary Outcomes (3)

  • Part A (Phase 1): Number of dose-limiting toxicities 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

  • 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 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

Secondary Outcomes (16)

  • Pharmacokinetics (PK) of ARV-806 (Part A): Area under the plasma or blood concentration-time profile during a dosing interval (AUC0-tau)

    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) (AUC0-last)

    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.

  • +11 more secondary outcomes

Study Arms (2)

Phase 1/Part A (Dose Escalation)

EXPERIMENTAL

Participants will receive ARV-806 at the assigned doses and regimen (weekly or every 2 weeks).

Drug: ARV-806

Phase 2/Part B (Dose Expansion)

EXPERIMENTAL

Participants will receive ARV-806 at one of up to 2 dose levels/regimens selected from Part A)

Drug: ARV-806

Interventions

Intravenous infusion at assigned dose and dosing schedule

Phase 1/Part A (Dose Escalation)Phase 2/Part B (Dose Expansion)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Clinical Trial Site

Phoenix, Arizona, 85004, United States

RECRUITING

Clinical Trial Site

Phoenix, Arizona, 85054, United States

RECRUITING

Clinical Trial Site

New Haven, Connecticut, 06510, United States

RECRUITING

Clinical Trial Site

Tampa, Florida, 33612, United States

RECRUITING

Clinical Trial Site

Indianapolis, Indiana, 46250, United States

NOT YET RECRUITING

Clinical Trial Site

Grand Rapids, Michigan, 49546, United States

RECRUITING

Clinical Trial Site

New York, New York, 10032, United States

RECRUITING

Clinical Trial Site

New York, New York, 10065, United States

RECRUITING

Clinical Trial Site

Huntersville, North Carolina, 28078, United States

RECRUITING

Clinical Trial Site

Cleveland, Ohio, 44106, United States

RECRUITING

Clinical Trial Site

Houston, Texas, 77030-7009, United States

RECRUITING

Clinical Trial Site

San Antonio, Texas, 78229, United States

RECRUITING

Clinical Trial Site

Salt Lake City, Utah, 84112, United States

RECRUITING

Clinical Trial Site

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic NeoplasmsCarcinoma, Non-Small-Cell LungColorectal NeoplasmsColonic NeoplasmsCholangiocarcinomaEndometrial NeoplasmsAdenocarcinoma Of EsophagusGallbladder NeoplasmsStomach NeoplasmsMelanomaOvarian NeoplasmsThyroid Neoplasms

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeUterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesBiliary Tract NeoplasmsBiliary Tract DiseasesGallbladder DiseasesStomach DiseasesNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsSkin DiseasesSkin and Connective Tissue DiseasesOvarian DiseasesAdnexal DiseasesGonadal DisordersHead and Neck NeoplasmsThyroid Diseases

Central Study Contacts

Study Design

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

Study Record Dates

First Submitted

June 9, 2025

First Posted

June 17, 2025

Study Start

May 29, 2025

Primary Completion (Estimated)

November 30, 2027

Study Completion (Estimated)

April 2, 2029

Last Updated

February 19, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations