A Study of ASN007 in Patients With Advanced Solid Tumors

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03415126
• Other study ID #: ASN007-101
• Status: Completed
• Phase: Phase 1
• Start date: January 19, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: July 2020
• Source: Asana BioSciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• ASN007: ascending doses
Oral drug for the treatment of advanced solid tumors
• ASN007 RD
Oral drug for the treatment of advanced solid tumors

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	NEXT Oncology	San Antonio	Texas
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Asana BioSciences

Country where clinical trial is conducted

United States, 

Outcome

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