Basket Trial ID’s Available Targeted Agents With Promise in Several Cancer Types

June 5, 2016

Matching targeted therapies to genetic abnormalities harbored by tumor types for which those therapies are not approved by the FDA might expand treatment options for some patients with advanced cancers.

[[{"type":"media","view_mode":"media_crop","fid":"49164","attributes":{"alt":"John D. Hainsworth, MD, presenting data from the MyPathway trial","class":"media-image","id":"media_crop_3674901540754","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5971","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","title":"John D. Hainsworth, MD, presenting data from the MyPathway trial","typeof":"foaf:Image"}}]]CHICAGO-Matching targeted therapies to genetic abnormalities harbored by tumor types for which those therapies are not US Food and Drug Administration (FDA)-approved might expand treatment options for some patients with advanced cancers, suggest early results from the open-label, phase IIa MyPathway trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract LBA11511).

“Clinical trials enrolling patients based on identified tumor molecular alterations, independent of tumor type, are feasible and important to benefit unmet medical needs,” said lead study author John D. Hainsworth, MD, a senior investigator at Sarah Cannon Research Institute in Nashville, Tennessee.

FDA-approved therapies are proliferating that target specific molecular aberrations in particular cancer types. These aberrations are also sometimes found in other cancer types, but approved targeted agents’ efficacies for these non-indicated tumor types remains unknown.  

MyPathway (NCT02091141) is an ongoing, non-randomized multicenter basket study designed to determine the efficacy of drugs that target the HER2, BRAF, Hedgehog, or EGFR pathways in non-indicated solid tumor types that harbor relevant genomic alterations. For example, non-melanoma patients harboring BRAF alterations were administered vemurafenib, which is indicated for melanoma harboring BRAF alterations, and non–lung cancer patients harboring EGFR mutations were administered erlotinib, which is indicated for non-small-cell lung cancer (NSCLC) with EGFR alterations.

Of the first 129 study participants enrolled, 29 patients with 12 different cancer types exhibited objective responses after receiving targeted therapies for non-indicated cancer types: 1 patient experienced a complete response, while 28 (22%) experienced partial responses and 40 (31%) had stable disease.

At a median follow-up of 6 months of treatment, 14 responders experienced disease progression; the other 15 responders had ongoing response up to 11 months. Durable responses were seen in HER2-amplified colorectal, bladder, and biliary cancers, as well as BRAF-mutated NSCLC.

“Although it is still early to draw conclusions, our findings suggest that, for example, HER2-targeted therapy could be expanded beyond the current indications of HER2-positive breast and gastric cancers,” said Dr. Hainsworth. “Our study gives strong early signals for activity of HER2-targeted therapy in HER2-amplified colorectal cancers (those with extra copies of the HER2 gene), and possibly other HER2-positive cancers.”

No new safety signals were noted.

The findings reflect “the incredible potential of precision medicine to help us identify new treatments, but it also underscores the need to explore this genomic-based testing and treatment approach in a learning environment, like a clinical trial,” commented Sumanta Kumar Pal, MD, an ASCO expert in developmental therapeutics.