Clinical Trial 24278

• Overview

  Study Title:

  A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, With and Without an Anti-EGFR Antibody, and With an Anti-EGFR Antibody and Chemotherapy, in Patients With Metastatic KRAS G12D-Mutated Colorectal Adenocarcinoma (TARGET-D 203)

  Summary:

  This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab or panitumumab and cetuximab plus mFOLFOX in patients with metastatic KRAS G12D - mutated Colorectal Cancer

  Objective:

  Parts A & B Primary Objectives: * To evaluate the anti-tumor efficacy of 900 mg VS-7375 monotherapy administered on a daily oral schedule and 900 mg VS-7375 combination therapy with intravenous (IV) cetuximab or panitumumab, in participants with metastatic KRAS G12D-mutated colorectal adenocarcinoma (CRC). * To characterize the safety and tolerability of VS-7375 monotherapy administered on a daily oral schedule and VS-7375 combination therapy with IV cetuximab or panitumumab in participants with metastatic KRAS G12D-mutated CRC. Secondary Objective: * To evaluate additional efficacy parameters of VS-7375 monotherapy administered on a daily oral schedule and VS-7375 combination therapy with IV cetuximab or panitumumab in participants with metastatic KRAS G12D-mutated CRC. Part C Primary Objective: * To characterize the safety, tolerability, and AE profile of VS-7375 administered on a daily oral schedule in combination with IV cetuximab and IV mFOLFOX6 in participants with metastatic KRAS G12D-mutated CRC. Secondary Objective: * To determine the efficacy of VS-7375 administered on a daily oral schedule in combination with IV cetuximab and IV mFOLFOX6 in participants with metastatic KRAS G12D-mutated CRC. All Parts Secondary Objective: * To continue to evaluate the PK of VS-7375 in participants with metastatic KRAS G12D-mutated CRC.

• Treatments

  Therapies:

  Chemotheraphy; Dual ON/OFF inhibitor targeting the KRAS G12D mutation; Monoclonal antibody that binds to EGFR

  Medications:

  5-fluorouracil (); Cetuximab (); Erbitux (Cetuximab); Oxaliplatin (); Panitumumab (); VS-7375 (); Vectibix (Panitumumab); eloxatin (Oxaliplatin); leucovorin ()

• Inclusion Criteria

  Inclusion Criteria:
  • Histopathology confirmed metastatic colorectal cancer
  • Measurable disease per RECIST 1.1
  • Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing) MM&> Must have received at least 1 standard chemotherapy for metastatic colorectal adenocarcinoma
  • Have documented disease progression during or following their most recent prior line of therapy
  • Have either stable disease, partial response (PR), or complete response (CR) by RECIST v1.1 as the best overall response (BOR) during at least 1 prior systemic therapy. 1L patients:
  • Treatment-naïve or received no more than 1 cycle of standard systemic therapy for metastatic disease.
  • Other criteria may apply

• Exclusion Criteria

  Exclusion Criteria:
  • Have any other documented co-existing common RAS mutation(s)
  • Prior anti-cancer treatment within 4 weeks or drug-specific timeline within first treatment dose, whichever shorter
  • Major surgery within 4 weeks of first treatment dose
  • Radiation therapy (RT) within 1 week of first treatment dose
  • Receipt of prior direct RAS inhibitor
  • Receipt of more than 1 investigational therapy
  • Untreated or symptomatic central nervous system metastasis
  • Receipt of strong CYP3A4 inhibitor/inducer or CYP3A4 sensitive substrates with narrow therapeutic index within 14 days or drug-specific timeline within first treatment dose, whichever is shorter
  • Receipt of PPI or H2 blocker within 5 days
  • Inability to swallow oral medication
  • Other protocol-defined inclusion/exclusion criteria may apply

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