A Study To Evaluate ARV-806 In Adults With Advanced Cancer That Has The KRAS G12D Mutation

Study Overview

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 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.

N/A

KRAS G12D Mutation
Advanced Solid Cancer

DRUG: ARV-806

ARV-806-101
2025-521062-10-00 (CTIS Identifier) (CTIS: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2025-06-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-06
First Submitted that Met QC Criteria 2025-06-09	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-08-11
First Posted (ACTUAL) 2025-06-17	Results First Posted N/A	Last Verified 2025-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1/Part A (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 (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

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Phase 1/Part A (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 (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

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
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.
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.
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: ARV-806 whole blood pre-dose concentration		At predefined intervals throughout the treatment period, up to approximately 6 months after first 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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Arvinas, Inc.

Phone Number: +14752245787

Email: clinicaltrialsARV-806@arvinas.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

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