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Clinical Trial 19703

Cancer Type: Multiple
Interventions:ASN007

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Zeynep Eroglu

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 1, Open-Label, Dose Finding Study of ASN007 in Patients with Advanced Solid Tumors

Summary

Objective

Primary Objectives Part A: - To evaluate the safety and tolerability of ASN007 in patients with advanced solid tumors, to characterize DLTs, to determine the maximum tolerated dose (MTD) and to recommend a Phase 2 dose (RP2D). Part B: - To evaluate the safety and tolerability of ASN007 in patients with advanced solid tumors with BRAF V600, KRAS, HRAS or NRAS mutations. Secondary Objectives - To evaluate the pharmacokinetic (PK) profile of ASN007 after single and multiple doses, - To evaluate preliminary evidence of clinical activity. Exploratory/Pharmacodynamic Objectives - To evaluate the effects of ASN007 on pharmacodynamic (PD) tumor biomarkers, - To explore mechanisms of intrinsic and acquired tumor resistance

Inclusion Criteria

  • Male or non-pregnant, non-lactating female patient at least 18 years of age at the time of consent;
  • Advanced or metastatic solid tumor (Part A)
  • Group 1: BRAF mutant melanoma (Part B)
  • Group 2: NRAS or HRAS mutant solid tumors(Part B)
  • Group 3: KRAS mutant CRC.(Part B)
  • Group 4: KRAS mutant NSCLC (Part B)Group 5: Pancreatic Ductal Adenocarcinoma (Part B)
  • Progressive disease after failure of or intolerant to all available standard systemic treatments that have shown a documented benefit in overall survival for their respective tumor type.
  • Screening hematology values of the following:
  • absolute neutrophil count ≥ 1000/μL,
  • platelets ≥ 100,000/μL,
  • hemoglobin ≥ 9 g/dL
  • Screening chemistry values of the following:
  • alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3.0 × upper limit of the normal (ULN),
  • total bilirubin ≤ 1.5 × ULN,
  • creatinine ≤ 1.5 × ULN,,
  • albumin ≥ 2.8 g/dL.
  • Screening heart function lab test
  • creatinine kinase - MB, troponin-I, and troponin-T within normal limits
  • Subject is willing and able to comply with all protocol required visits and assessments, including biopsy if assigned.

  • Exclusion Criteria

  • Prior treatment with ASN007 or another ERK1/2 inhibitor
  • Known hypersensitivity to ASN007 or its excipients;
  • Part B: Prior treatment with a RAF or MEK pathway inhibitor, except BRAFmutant melanoma (Group 1)
  • Prior chemotherapy, targeted therapy or monoclonal antibody therapy within 3 weeks of start of study treatment (Day1), or 5 half-lives, whichever is shorter.
  • Concurrent or prior bone marrow factors (e.g. G-CSF, GM-CSF or erythropoietin) within 3 weeks prior to Day 1 of treatment.
  • Febrile neutropenia or serious persistent infection within 2 weeks prior to Day 1 of treatment
  • Failure to recover from major surgery or traumatic injury within 4 weeks or minor surgery within 2 weeks prior to Day 1 of treatment.
  • History of or current evidence / risk of retinal vein occlusion (RVO) central serous retinopathy (CSR), or glaucoma with intraocular pressures ≥ 21 mmHg or other pre-existing ocular conditions that may put the patient at risk for ocular toxicities
  • Known central nervous system (CNS) primary tumor, CNS metastases or carcinomatous meningitis (Part A). Patients may be enrolled with CNS metastasis in certain circumstances in Part B.
  • Clinically significant heart disorders including an ejection fraction of >Other serious uncontrolled conditions such as fungal, bacterial or viral infection; HIV, Hepatitis B or C, bleeding disorders, interstitial lung disease