A Study of ASN007 in Patients With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Cancer; Malignancy; Neoplasia; Colon Cancer; Colonic Neoplasms; Neoplasm; Neoplasm Metastasis; Colon Cancer Liver Metastasis; Metastatic Cancer; Metastatic Melanoma
• Interventions: Drug: ASN007 RD

• Registration Number: NCT03415126
• Lead Sponsor: Asana BioSciences

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.

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 Timeline

• Study First Submitted: 2018-01-15
• Study Start: 2018-01-19
• Study First Submitted QC: 2018-01-29
• Study First Posted: 2018-01-30
• Primary Completion: 2020-06-30
• Study Completion: 2020-06-30
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-07
• Last Update Posted: 2020-07-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ASN007 RD: KRAS mutant Melanoma	ASN007 RD	Patients with BRAF mutant metastatic melanoma will receive the recommended dose from Part A.
ASN007 RD: KRAS mutant metastatic CRC	ASN007 RD	Patients with KRAS mutant CRC will receive the recommended dose from Part A
ASN007 RD: NRAS mutant Melanoma	ASN007 RD	Patients with NRAS and HRAS mutant solid tumors will receive the recommended dose from Part A.
ASN007 RD: KRAS mutant NSCLC	ASN007 RD	Patients with KRAS mutant NSCLC will receive the recommended dose from Part A
ASN007 RD: Metastatic Pancreatic Cancer	ASN007 RD	Patients with pancreatic adenocarcinoma will receive the recommended dose from Part A
ASN007 RD: MEK, All BRAF, BRAF-fusion cancers	ASN007 RD	Patients with solid tumors will receive the recommended dose from Part A

Primary Outcome Measures

Name	Time	Method
Part A: Determine the maximum tolerated dose (MTD) of ASN007	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
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.	First 6 months	This is the primary endpoint for Part B.

Secondary Outcome Measures

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

Trial Locations

Locations (5)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

South Texas Accelerated Research Therapeutics; 🇺🇸 San Antonio, Texas, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

H. Lee Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States