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Developmental therapeutics

4813 - A Phase 1 PK/PD Study of ASN003, a novel highly selective BRAF and PI3K inhibitor, in Patients with Advanced Solid Tumors.

Date

09 Sep 2017

Session

Developmental therapeutics

Topics

Clinical Research

Presenters

Drew Rasco

Citation

Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367

Authors

D. Rasco1, R. Sullivan2, N. Lakhani3, S. Reddy4, N. Rao4, L. Denis4, A. Tolcher1, K.T. Flaherty5

Author affiliations

  • 1 Medical Oncology, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 2 Department Of Oncology, Massachusetts General Hospital Cancer Center, 2114 - Boston/US
  • 3 Medical Oncology, South Texas Accelerated Research Therapeutics (START), 49503 - Grand Rapids/US
  • 4 Oncology, Asana Biosciences, 08648 - Lawrenceville/US
  • 5 Termeer Center For Targeted Therapies, Massachusetts General Hospital Cancer Center, 02114 - Boston/US
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Resources

Abstract 4813

Background

RAS-RAF-MEK and PI3K-AKT-mTOR are two major pathways involved in tumor cell signaling and growth. Components of these pathways are frequently mutated in a broad range of tumors. ASN003 is a highly selective and potent (low nM IC50) inhibitor of BRAF and PI3K-α and -d (low affinity for PI3K-b). ASN003 shows strong antitumor activity in tumor models harboring BRAF and PIK3CA or PTEN mutations, and also in PDX models that are resistant to selective BRAF and MEK inhibitors.

Methods

Oral ASN003 once daily is being evaluated for safety/tolerability and preliminary efficacy in eligible patients with advanced solid tumors using an accelerated dose titration design (Part A) and enrolling cohorts of melanoma, CRC and NSCLC patients with a BRAF, PIK3CA or PTEN mutation at MTD (Part B). Eligibility criteria include HbA1c ≤ ULN or fasting glucose

Results

Patient accrual is ongoing. To date, seven eligible patients are enrolled in dose levels ranging from 10 – 120 mg QD. ASN003 has been well tolerated. Treatment-related adverse events (TRAEs) were mild (G1) to moderate (G2). TRAEs include diarrhea (G2) (n = 1), nausea/vomiting (G1) and dry mouth/lips/skin (G1). Transient G1 elevation of glucose and insulin c-peptide levels has been noted in 1 pt. No G3/4 AEs have been observed to date. The PK profile showed excellent, systemic exposure at steady state at all doses (Cmax up to 930 ng/mL, AUC0-T up to 18998 ng.h/mL at 80 mg QD) and a half-life of > 12 hour. Dose escalation is ongoing.

Conclusions

ASN003 is a novel small molecule, with uniquely selective and potent inhibition of BRAF, PI3-α and -d kinases. To date, ASN003 was well tolerated at doses up to 120 mg QD and achieved good systemic exposure. Updated and detailed clinical safety/efficacy and PK/PD results will be presented.

Clinical trial identification

NCT02961283

Legal entity responsible for the study

Asana BioSciences

Funding

Asana BioSciences

Disclosure

S. Reddy, N. Rao, L. Denis: Employee and Stock Ownership Asana BioSciences. A. Tolcher, K.T. Flaherty: Member of Scientific Advisory Board Asana BioSciences. All other authors have declared no conflicts of interest.

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