Clinical Trial 23659

• Overview

  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

  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.

  Objective:

  Part A Phase 1 Dose Escalation Primary Objectives: - To evaluate the safety and tolerability of ARV-806 in successive cohorts of patients with KRAS G12D mutated solid tumors, to estimate the MTD or maximum administered dose, and select the potential RP2D/schedule(s) Secondary Objectives: - To characterize the PK of ARV-806 following single and multiple IV dosing - To explore the antitumor activity of ARV-806 in the study population Part B Phase 2 Dose Expansion Primary Objectives: - To evaluate the antitumor activity of ARV-806 in patients with KRAS G12D mutated advanced PDAC in one or more dose cohort(s) to support further RP2D dose optimization Secondary Objectives: - To evaluate safety endpoints in one or more dose cohort(s) to support further RP2D dose optimization - To characterize sparse PK of ARV-806 to support further RP2D dose optimization - To further explore the antitumor activity of ARV-806 in the study population to support further RP2D dose optimization

• Treatments

  Therapies:

  PROTAC degrader

  Medications:

  ARV-806 ()

• Inclusion 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 (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.
  • Other criteria may apply

• Exclusion Criteria

  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
  • Other criteria may apply

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