Geoffrey R. Oxnard
LOXO-292 appeared well tolerated and demonstrated antitumor activity among patients with heavily pretreated RET fusion-positive non-small cell lung cancer, according to updated interim results of a global, phase 1/phase 2 trial presented at International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.
Researchers reported initial clinical data from the LIBRETTO-001 dose escalation/expansion study of LOXO-292 (Loxo Oncology) — an oral and selective agent in clinical development for cancers that harbor abnormalities in the rearranged during transfection (RET) kinase — at ASCO Annual Meeting in June.
The latest data on 38 patients with RET fusion-positive NSCLC include 3.5 months of additional follow-up, as well as the first follow-up scans of the eight patients most recently enrolled.
Patients had a median of three prior systemic treatment regimens, and 39% had received prior platinum-based chemotherapy and anti-PD-1/PD-L1 therapy.
With a median follow-up of 9.5 months, 96% of responding patients remained on therapy and 92% of patients remained in response.
Researchers observed an overall response rate of 68% (95% CI, 51-83).
“It has been just a few months since ASCO, but the additional follow-up afforded by [these] data provide encouraging evidence that LOXO-292 can deliver durable responses in heavily pretreated patients,” Geoffrey R. Oxnard, MD, associate professor of medicine at Harvard Medical School and thoracic oncologist at Dana-Farber Cancer Institute, said in a company-issued press release. “It was additionally reassuring to see that LOXO-292 appears to be well tolerated at the phase 2 dose of 160 mg [twice daily]. With breakthrough therapy designation in hand, LOXO-292 is moving rapidly through clinical development, so it is important for investigators and patients to pay attention to this emerging target and class of medicines.”
The LIBRETTO-001 trial included a total of 82 patients with advanced solid tumors. Among those evaluable for safety, researchers observed mostly grade 1 adverse events that they deemed not related to treatment.
The most common grade 3 adverse events included diarrhea and headache (both 1%). The most common grade 1 or grade 2 events included diarrhea (grade 1, 15%; grade 2, 7%) fatigue (9%; 13%), dry mouth (21%; 0%), constipation (17%; 2%), hypomagnesemia (12%; 1%), cough (11%; 1%), headache (10%; 1%) and nausea (9%; 4%).
Researchers observed four patients with treatment-related grade 3 tumor lysis syndrome, increased alanine transaminase/aspartate transaminase, diarrhea and thrombocytopenia, which resolved with dose interruption. – by Cassie Homer
Oxnard, GR, et al. Abstract OA12.07. Presented at: International Association for the Study of Lung Cancer’s World Conference on Lung Cancer; Sept. 23-26, 2018; Toronto, Canada.
Disclosure: Oxnard reports speaker, advisory or other roles with AstraZeneca, DropWorks, GRAIL, Inivata and Takeda/Ariad; honoraria from Guardant and Sysmex; being a co-author on a patent held by Dana-Farber Cancer Institute for a plasma genotyping approach. Please see the abstract for all other authors’ relevant financial disclosures.