Promising Efficacy and Safety for Selpercatinib, a RET Fusion Inhibitor, in Advanced NSCLC

The following article features coverage from the IASLC 2019 World Conference on Lung Cancer meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Updated results from a phase 1/2 study evaluating the safety and efficacy of the investigational RET fusion inhibitor, LOXO-292 — recently named selpercatinib — showed a high response rate and a long duration of response in patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC). The findings from this study were presented at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain.^1,2

Although rare, the RET gene fusion has been identified as an oncogenic driver in NSCLC. Nevertheless, no RET-targeted therapies are currently approved by the US Food and Drug Administration (FDA) in the setting of advanced NSCLC.²

The LIBRETTO-001 study (ClinicalTrials.gov Identifier: NCT03157128) investigated patients with advanced solid tumors, RET fusion-positive solid tumors, medullary thyroid cancer, and other tumors with RET activation. Determination of the maximum-tolerated dose and phase 2 dose of LOXO-292 [phase 1], and overall response rate (ORR) [phase 2] are primary study end points, and characterization of treatment-related adverse events is a key secondary end point of the study [phase 1/2].

On the basis of early analyses of data from this trial, the FDA granted Breakthrough Therapy designation to LOXO-292 in patients with pretreated metastatic RET fusion-positive NSCLC or RET-mutant medullary thyroid cancer.³

In the primary analysis cohort of 105 patients with advanced RET fusion-positive NSCLC who had received pretreatment with platinum-based chemotherapy and were subsequently treated with selpercatinib in the LIBRETTO-001 study, the ORR was 68%. Notably, these responses were durable, with a median duration of response of 20.3 months at a median follow-up of 8 months.

Interestingly, 10 of the 11 patients (91%) in the NSCLC cohort with measurable brain metastases at baseline responded to treatment with selpercatinib.

In the entire safety cohort of 531 patients, most adverse event were grade 1/2, and only 1.7% of patients discontinued selpercatinib due to a treatment-related adverse event.

“In this large cohort, selpercatinib’s response rate, durability, robust intracranial activity, and safety show promise. Furthermore, this continues to confirm that RET fusions are clinically targetable alterations, placing them in the company of 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 NSCLC,” noted Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center, New York, NY.²

Read more of Cancer Therapy Advisor‘s coverage of the IASLC annual meeting by visiting the conference page.

References

1. Drilon A, Oxnard GR, Wirth L, et al. A phase 1/2 trial of LOXO-292 in patients with RET fusion-positive lung cancers. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract PL02.08.
2. International Association for the Study of Lung Cancer. Registrational data from the LIBRETTO-1 trial demonstrate compelling and durable activity of selpercatinib (LOXO-292) in RET fusion-positive lung cancer. Published September 9, 2019. Accessed September 9, 2019.
3. The ASCO Post. FDA grants breakthrough therapy designation to LOXO-292 for treatment of lung and thyroid cancers. Accessed September 9, 2019.