A Study of ASN007 in Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT03415126
• Recruitment Status: Completed
• First Posted: January 30, 2018
• Last Update Posted: July 9, 2020
• Sponsor: Asana BioSciences
• Information provided by (Responsible Party): Asana BioSciences

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: ASN007: ascending doses; Drug: ASN007 RD	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Dose-Finding Study Of ASN007 In Patients With Advanced Solid Tumors
• Actual Study Start Date: January 19, 2018
• Actual Primary Completion Date: June 30, 2020
• Actual Study Completion Date: June 30, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Part A: Determine the maximum tolerated dose (MTD) of ASN007 [ Time Frame: First 21 days ]
   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
2. 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. [ Time Frame: First 6 months ]
   This is the primary endpoint for Part B.

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Florida

H. Lee Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States, 78229

NEXT Oncology

San Antonio, Texas, United States, 78240

Sponsors and Collaborators

Asana BioSciences

Investigators

• Study Director: Medical Monitor; Asana BioSciences

More Information

• Responsible Party: Asana BioSciences
• ClinicalTrials.gov Identifier: NCT03415126
• Other Study ID Numbers: ASN007-101
• First Posted: January 30, 2018
• Last Update Posted: July 9, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Asana BioSciences:

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

Additional relevant MeSH terms:

Lung Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Pancreatic Neoplasms; Colonic Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Pathologic Processes; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases