Treatment with selpercatinib (LOXO-292) was associated with high objective response rate (ORR) in heavily pretreated patients with RET fusion-positive non-small cell lung cancer (NSCLC), according to research presented at the IASLC 2019 World Conference on Lung Cancer.

Researchers from Memorial Sloan Kettering Cancer Center presented data from the LIBRETTO-001 (LOXO-292 Investigated to Block RETaltered Tumors) clinical trial, a global phase 1/2 study evaluating selpercatinib in RET fusion-positive NSCLC patients. The trial included a dose escalation phase (phase 1) and a dose expansion phase (phase 2) with a primary end point of ORR. Secondary end points include duration of response (DoR), progression free survival (PFS) and safety. 

Registrational data presented included the primary analysis of the first 105 enrolled patients with RET fusion-positive NSCLC previously treated with platinum-based chemotherapy. Results showed that selpercatinib therapy was associated with an ORR of 68% (95% CI, 58% to 76%) in a heavily pretreated patient population. In the subset of patients with brain metastases, treatment with selpercatinib  demonstrated a CNS ORR of 91% (95% CI, 59% to 100%). 

The median DoR and PFS as of the data cut-off date of June 17, 2019 were 20.3 months (95% CI, 13.8 to 24) and 18.4 months (95% CI, 12.9 to 24.9), respectively. Selpercatinib was found to be well-tolerated with only 9 patients discontinuing therapy due to treatment-related toxicity. Common adverse effects included dry mouth, diarrhea, hypertension, elevated liver enzymes, fatigue, constipation, and headache. 

“In this large cohort, selpercatinib’s response rate, durability, robust CNS activity, and safety show promise,” Alexander Drilon, MD, lead investigator, Memorial Sloan Kettering Cancer Center in New York City reported. “Furthermore, this continues to confirm that RET fusions are clinically targetable alterations, placing them in the company of activating EGFR/ALK/ROS1 alterations. We are encouraged by these data as there is currently an unmet need to provide genomically-tailored therapy to patients with RET fusion-positive NSCLCs.”

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Selpercatinib (LOXO-292) is a potent, highly selective, oral investigational agent in clinical development for the treatment of cancers with genomic alterations in the Rearranged During Transfection (RET) gene. The FDA previously granted selpercatinib Breakthrough Therapy designation for the treatment of patients with: metastatic RET fusion-positive NSCLC who require systemic therapy and have progressed following platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy; RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, have progressed following prior treatment and with no acceptable alternative options; and advanced RET-fusion-positive thyroid cancer who require systemic therapy, have progressed following prior treatment and with no acceptable alternatives.

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Drilon A, Oxnard G, Wirth L, et al. Registrational results of Libretto-001: a phase 1/2 trial of LOXO-292 in patients with RET fusion-positive lung cancers. Presented at: The IASLC 2019 World Conference on Lung Cancer (WCLC) of the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona Spain. Abstract PL02.08.