LIBRETTO-431
Research type
Research Study
Full title
A Multicenter, Randomized, Open-label, Phase 3 Trial Comparing LOXO-292 to Platinum-Pemetrexed Chemotherapy Plus Investigator’s Choice of Pembrolizumab in Patients with Advanced, Treatment-Naïve RET Fusion-Positive Non-Small Cell Lung Cancer
IRAS ID
271816
Contact name
Alan James Lenox-Smith
Contact email
Sponsor organisation
Eli Lilly and Company
Eudract number
2019-001979-36
Duration of Study in the UK
5 years, 11 months, 2 days
Research summary
Lung cancer is the most common form of cancer and the most common cause of cancer deaths worldwide, with 2.09 million new cases and 1.76 million deaths in 2018. Approximately 80% to 85% of lung cancers are Non-Small Cell Lung Cancers (NSCLC). Currently the standard of care treatment for patients with NSCLC in most cases is platinum-based chemotherapy regimens. Typical response rates to these regimens are 20% to 30% with a median progression free survival of 5 months. New advances have indicated that some patients may gain additional benefit by adding immunotherapy to the standard platinum-based chemotherapy regimens. Additionally, some patients have specific genomic changes in their tumours that drive the growth of the tumour. Drugs that target these changes have been approved as an effective way to treat patients with these alterations (e.g. EGFR, ROS1, ALK).
In a similar manner, genetic mutations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signalling and uncontrolled cell growth. This dependency, often referred to as “oncogene addiction,” renders such tumours highly susceptible to small molecule inhibitors targeting RET. However, RET fusions are rare and only have been identified in approximately 2% of non-small cell lung cancer patients.
LOXO-292 is a highly potent and specific oral investigational drug currently in clinical development for the treatment of patients with cancers that harbour abnormalities in RET kinase. LOXO-292 was designed to inhibit native RET signalling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 has demonstrated an acceptable safety profile and evidence of durable antitumor activity in patients with advanced NSCLC. As a result, LOXO-292 may be of benefit as an initial treatment with advanced or metastatic RET fusion-positive NSCLC. In a phase 1 / 2 trial, LOXO-292 demonstrated encouraging, early evidence of durable activity, with 68% (26/38) of RET fusion positive NSCLC having a response.
Study J2G-MC-JZJC is a randomized, open-label phase 3 trial comparing LOXO-292 to platinum based and pemetrexed therapy with or without pembrolizumab. The study will allow patients whose disease has progressed on chemotherapy with or without pembrolizumab to crossover and receive LOXO-292.
REC name
London - South East Research Ethics Committee
REC reference
19/LO/1795
Date of REC Opinion
15 Nov 2019
REC opinion
Unfavourable Opinion