Pipeline

LOXO-292

LOXO-292 (RET inhibitor)


LOXO-292 is a highly selective RET inhibitor.

LOXO-292 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions have been identified in approximately 2% of non-small cell lung cancer, approximately 10-20% of papillary thyroid cancer, and a subset of colon and other cancers. RET point mutations account for approximately 60% of medullary thyroid cancer. 

RET gene fusions, much like TRK gene fusions, occur when the RET gene abnormally fuses to another gene. The hybrid gene that is created as a result drives tumor growth. 

Both RET fusion and select RET mutated cancers are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as “oncogene addiction,” renders such tumors highly susceptible to small molecule inhibitors targeting RET. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 is currently being studied in a Phase 1 trial. For more information about the LOXO-292 clinical trial, please refer to clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology RET Physician and Patient Clinical Trial Hotline for more information about the LOXO-292 clinical trial at 1-855-RET-4-292 or email clinicaltrials@loxooncology.com.


LOXO-292 Phase 1 Trial

LOXO-292 is currently being evaluated in a global, multi-center Phase 1 trial in patients with advanced solid tumors.

For more information about the LOXO-292 clinical trial, please refer to clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology RET Physician and Patient Clinical Trial Hotline for more information about the LOXO-292 clinical trial at 1-855-RET-4-292 or email clinicaltrials@loxooncology.com.

Policy for Access to Investigational Agents

Loxo Oncology is committed to helping patients who have not responded to available therapies and may benefit from its investigational therapies. Loxo Oncology’s Policy for Access to Investigational Agents describes the principles that the company will follow when considering a request, view here.


Data presented at the 2016 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics illustrated the potency, specificity, and favorable in vivo properties in animals of LOXO-292, our clinical candidate. Read the poster presented at AACR-NCI-EORTC here.

Data presented at the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics showed that our RET inhibitors offer high oral bioavailability and favorable PK properties in animals. Several demonstrated potent inhibition of RET in enzyme and cellular assays, with minimal activity against highly related kinases. Read the poster presented at AACR-NCI-EORTC here.

Initial clinical data for LOXO-292 were recently presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer. The presentation described the first two patients with RET-fusion lung cancer with and without brain metastases treated with LOXO-292. Both patients had disease progression while receiving prior multi-kinase inhibitors (MKIs). On LOXO-292, both patients achieved partial responses. The first patient was previously treated with RXDX-105, enrolled on the first dose cohort of the Phase 1 trial, received LOXO-292 20 mg daily, and demonstrated a RECIST confirmed partial response. The second patient was previously treated with alectinib (starting at 600 mg twice daily and increased to 900 mg twice daily) and experienced disease progression systemically and in the brain. Due to the rapidly progressive nature of the brain metastases, the patient was ineligible for the Phase 1 trial and received LOXO-292 in doses ranging from 20-100 mg twice daily under an intra-patient dose escalation single patient protocol. The patient demonstrated a RECIST confirmed partial response, including a response in the brain. In this early, two patient data set, LOXO-292 has been well-tolerated, with no adverse events attributed to LOXO-292. View the presentation here.