Clinical Trials /

A Study of ASN007 in Patients With Advanced Solid Tumors

NCT03415126

Description:

The study is divided into two parts. The first part of the study will test various doses of ASN007 to find out the highest safe dose to test in five specific groups. The second part of the study will test how well ASN007 can control cancer.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ASN007 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1, Open-Label, Dose-Finding Study Of ASN007 In Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ASN007-101
  • NCT ID: NCT03415126

Conditions

  • Cancer
  • Malignancy
  • Neoplasia
  • Neoplasm
  • Neoplasm Metastasis
  • Colon Cancer
  • Colonic Neoplasms
  • Colon Cancer Liver Metastasis
  • Metastatic Cancer
  • Metastatic Melanoma
  • Metastatic Colon Cancer
  • Metastatic Lung Cancer
  • Non Small Cell Lung Cancer Metastatic
  • Pancreatic Cancer
  • Pancreas Cancer
  • Pancreas Adenocarcinoma
  • Pancreas Neoplasm
  • Metastatic Nonsmall Cell Lung Cancer
  • Metastatic Pancreatic Cancer

Interventions

DrugSynonymsArms
ASN007: ascending dosesASN007 ascending doses
ASN007 RDASN007 RD: KRAS mutant Melanoma

Purpose

The study is divided into two parts. The first part of the study will test various doses of ASN007 to find out the highest safe dose to test in five specific groups. The second part of the study will test how well ASN007 can control cancer.

Detailed Description

      Part A is a dose escalation study to determine a safe and tolerable dose of ASN007 for
      patients with advanced solid tumors. Part A will also describe how the body works on
      ASN007(pharmacokinetics) and the effects of ASN007 on the body (pharmacodynamics) of ASN007,
      through blood sampling and optional biopsies..

      Part B of the study will enroll patients with particular tumor types and genetic mutations
      for treatment at the Recommended Phase 2 Dose. Part B will enroll patients in five groups of
      fifteen patients each:

      Group 1: Patients with metastatic BRAF mutated melanoma Group 2: Patients with metastatic
      NRAS and HRAS mutated solid tumors Group 3: Patients with metastatic KRAS mutated colorectal
      cancer (CRC) Group 4: Patients with metastatic KRAS mutated non-small cell lung cancer
      (NSCLC) Group 5: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) Patients
      with melanoma will be required to have pre-dose and post-dose biopsies.

      Group 6: Patients with metastatic MEK1, BRAF V600E, non-BRAF V600E solid tumors or BRAF
      fusions without prior treatment with BRAF, MEK, ERK inhibitors
    

Trial Arms

NameTypeDescriptionInterventions
ASN007 ascending dosesExperimentalPatients will receive escalating doses of ASN007 to identify the best dose.
  • ASN007: ascending doses
ASN007 RD: KRAS mutant MelanomaExperimentalPatients with BRAF mutant metastatic melanoma will receive the recommended dose from Part A.
  • ASN007 RD
ASN007 RD: NRAS mutant MelanomaExperimentalPatients with NRAS and HRAS mutant solid tumors will receive the recommended dose from Part A.
  • ASN007 RD
ASN007 RD: KRAS mutant metastatic CRCExperimentalPatients with KRAS mutant CRC will receive the recommended dose from Part A
  • ASN007 RD
ASN007 RD: KRAS mutant NSCLCExperimentalPatients with KRAS mutant NSCLC will receive the recommended dose from Part A
  • ASN007 RD
ASN007 RD: Metastatic Pancreatic CancerExperimentalPatients with pancreatic adenocarcinoma will receive the recommended dose from Part A
  • ASN007 RD
ASN007 RD: MEK, All BRAF, BRAF-fusion cancersExperimentalPatients with solid tumors will receive the recommended dose from Part A
  • ASN007 RD

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent obtained prior to any study-related procedure being
             performed;

          -  Male or non-pregnant, non-lactating female patient at least 18 years of age at the
             time of consent;

          -  Eastern Cooperative Oncology Group Performance Status 0-1 (Part A) and PS 0-2 (Part B)

          -  Histologically or cytologically confirmed

          -  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.

          -  Measurable or evaluable disease per RECIST v1.1

          -  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 < 50%

          -  Other serious uncontrolled conditions such as fungal, bacterial or viral infection;
             HIV, Hepatitis B or C, bleeding disorders, interstitial lung disease,

          -  Any other condition that might place the patient at undue risk.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Determine the maximum tolerated dose (MTD) of ASN007
Time Frame:First 21 days
Safety Issue:
Description:The MTD will be determined by evaluating the number of subjects with treatment related dose limiting toxicity. This is the primary endpoint of Part A

Secondary Outcome Measures

Measure:Calculate the pharmacokinetic area under the plasma concentration (AUC) of ASN007
Time Frame:First 21 days
Safety Issue:
Description:Calculate the amount of ASN007 in the bloodstream
Measure:Calculate the maximum plasma concentration (Cmax) at steady state.
Time Frame:First 21 days
Safety Issue:
Description:Calculate the maximum amount of ASN007 in the bloodstream
Measure:Calculate the terminal elimination rate (T 1/2).
Time Frame:First 21 days
Safety Issue:
Description:Calculate how fast ASN007 leaves the body

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Asana BioSciences

Trial Keywords

  • KRAS mutant
  • NRAS mutant
  • BRAF mutant
  • HRAS mutant
  • ERK 1/2 inhibitor

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