A Study of ASN007 in Patients With Advanced Solid Tumors

A Phase 1, Open-Label, Dose-Finding Study Of ASN007 In Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Neoplasm Metastasis; Pancreatic Cancer; Metastatic Cancer; Metastatic Lung Cancer; Pancreas Adenocarcinoma; Metastatic Melanoma; Colon Cancer; Colonic Neoplasms; Pancreas Cancer; Non Small Cell Lung Cancer Metastatic; Neoplasm; Pancreas Neoplasm; Metastatic Pancreatic Cancer; Metastatic Colon Cancer; Malignancy; Colon Cancer Liver Metastasis; Neoplasia; Metastatic Nonsmall Cell Lung Cancer
• Intervention / Treatment: Drug: ASN007: ascending doses; Drug: ASN007 RD

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

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics
    • San Antonio, Texas, United States, 78240
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASN007 ascending doses; Patients will receive escalating doses of ASN007 to identify the best dose.	Drug: ASN007: ascending doses; Oral drug for the treatment of advanced solid tumors
Experimental: ASN007 RD: KRAS mutant Melanoma; Patients with BRAF mutant metastatic melanoma will receive the recommended dose from Part A.	Drug: ASN007 RD; Oral drug for the treatment of advanced solid tumors
Experimental: ASN007 RD: NRAS mutant Melanoma; Patients with NRAS and HRAS mutant solid tumors will receive the recommended dose from Part A.	Drug: ASN007 RD; Oral drug for the treatment of advanced solid tumors
Experimental: ASN007 RD: KRAS mutant metastatic CRC; Patients with KRAS mutant CRC will receive the recommended dose from Part A	Drug: ASN007 RD; Oral drug for the treatment of advanced solid tumors
Experimental: ASN007 RD: KRAS mutant NSCLC; Patients with KRAS mutant NSCLC will receive the recommended dose from Part A	Drug: ASN007 RD; Oral drug for the treatment of advanced solid tumors
Experimental: ASN007 RD: Metastatic Pancreatic Cancer; Patients with pancreatic adenocarcinoma will receive the recommended dose from Part A	Drug: ASN007 RD; Oral drug for the treatment of advanced solid tumors
Experimental: ASN007 RD: MEK, All BRAF, BRAF-fusion cancers; Patients with solid tumors will receive the recommended dose from Part A	Drug: ASN007 RD; Oral drug for the treatment of advanced solid tumors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Determine the maximum tolerated dose (MTD) of ASN007	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	First 21 days
Part B: evaluate the overall response rate (number of Complete Responses + Partial Responses) in subjects receiving ASN007 for the treatment of metastatic melanoma, CRC, NSCLC, or pancreatic cancer.	This is the primary endpoint for Part B.	First 6 months

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the change from baseline in the intensity of phosphorylated ribosomal S6 kinase (RSK) found in tumor biopsies.	Evaluate the effect of ASN007 on biomarkers	Through the study, average 6 months
Evaluate the change from baseline in the amount of circulating tumor DNA	Evaluate the effect of ASN007 on biomarkers	Every 8 weeks for the first 24 weeks, then every 12 weeks for up to 1 year

Collaborators and Investigators

• Sponsor: Asana BioSciences
• Investigators: Study Director: Medical Monitor, Asana BioSciences

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2018
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: January 15, 2018
• First Submitted That Met QC Criteria: January 29, 2018
• First Posted (Actual): January 30, 2018

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: KRAS mutant; NRAS mutant; BRAF mutant; HRAS mutant; ERK 1/2 inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Neoplastic Processes; Colorectal Neoplasms; Pancreatic Diseases; Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Pancreatic Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: ASN007-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No