Clinical trial NCT07023731: A Study to Evaluate ARV-806 in Adults With Advanced Cancer That Has the KRAS G12D Mutation
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: KRAS G12D Mutation
Advanced Solid Cancer
Keywords: KRAS G12D Mutation
Advanced Solid Tumors
KRAS G12D Mutated Advanced Solid Tumors
KRAS G12D Mutated Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
PDAC
Non-Small Cell Lung Cancer
NSCLC
Colorectal Cancer
Colon Cancer
CRC
Appendiceal Carcinoma
Cholangiocarcinoma
Endometrial Cancer
Esophageal Adenocarcinoma
Gallbladder Cancer
Gastric Cancer
Melanoma
Ovarian Cancer
Small Bowel Adenocarcinoma
Thyroid Cancer
advanced cancer
KRAS
G12D mutation
Pancreas cancer
Lead sponsor: Arvinas Inc.
Sponsor class: INDUSTRY
First posted: 2025-06-17
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 (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 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

Primary outcomes:
measure: Part A (Phase 1): Number of dose-limiting toxicities of ARV-806
timeFrame: 28 days from first ARV-806 administration
measure: Part A (Phase 1): Number of participants with Adverse Events (AEs)
timeFrame: From the study baseline to at least 28 days after last dose of ARV-806
measure: Part B (Phase 2): Overall Response Rate (ORR)
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARV-806 (Part A): Area under the plasma or blood concentration-time profile during a dosing interval (AUC0-tau)
timeFrame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
measure: 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)
timeFrame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
measure: PK of ARV-806 (Part A): Maximum plasma or blood concentration (Cmax)
timeFrame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
measure: PK of ARV-806 (Part A): Minimum observed concentration (Cmin)
timeFrame: Timeframe: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
measure: PK of ARV-806 (Part A): Plasma or blood clearance (CL)
timeFrame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
measure: PK of ARV-806 (Part A): Time for Cmax (Tmax)
timeFrame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
measure: PK of ARV-806 (Part A): Volume of distribution (Vd)
timeFrame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
measure: Part A: Overall Response Rate (ORR)
timeFrame: Approximately 2 years
measure: Part A: Time to Response (TTR)
timeFrame: Approximately 2 years
measure: Part A: Duration of Response (DOR)
timeFrame: Approximately 2 years
measure: Part A: Disease Control Rate (DCR)
timeFrame: Approximately 2 years
measure: Part B: Number of participants with AEs
timeFrame: From the study baseline to at least 28 days after last dose of ARV-806
measure: Part B: ARV-806 whole blood pre-dose concentration
timeFrame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
measure: Part B: Time to Response (TTR)
timeFrame: Approximately 2 years
measure: Part B: Duration of Response (DOR)
timeFrame: Approximately 2 years
measure: Part B: Disease Control Rate (DCR)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Fairfax
country: United States
facility: Clinical Trial Site
state: Virginia
Study officials:
References: