Benzinga | Sep 8, 2021 04:01PM EDT

Amgen Presents New Data From Thoracic Oncology Portfolio At WCLC21

Amgen (NASDAQ:AMGN) today announced results from two analyses of the Phase 2 CodeBreaK 100 clinical trial evaluating LUMAKRAS(tm) (sotorasib), the first and only KRASG12C inhibitor approved in the U.S., in the treatment of previously treated patients with advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). These new analyses, respectively, provide encouraging evidence of durable systemic anticancer activity in patients with previously treated, stable brain metastases with LUMAKRAS, as well as insights into biomarkers of LUMAKRAS response. Together with a poster describing a recently initiated clinical study of the investigational half-life extended (HLE) bispecific T cell engager (BiTE(r)) molecule acapatamab (formerly AMG 160) in patients with NSCLC, these data are being featured during the virtual 2021 World Conference on Lung Cancer (WCLC21) hosted by the International Association for the Study of Lung Cancer (IASLC).

"Amgen is expanding the reach, impact and potential of our innovative therapies to personalize care for patients with historically difficult-to-treat cancers like lung cancer," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We are pleased to present additional analyses for LUMAKRAS, our newly approved KRASG12C inhibitor, as well as a trial-in-progress poster for acapatamab, our investigational BiTE molecule being studied in NSCLC and other solid tumors. Of the data presented at WCLC, we are particularly encouraged by the first evaluation of LUMAKRAS' ability to maintain stabilization of brain metastases in patients with previously treated, stable brain metastases. We look forward to the results from our CodeBreaK 101 study where we are studying a cohort of KRAS G12C-mutated NSCLC patients with untreated, active brain metastases to better understand the clinical benefit of LUMAKRAS."

New Analyses From the LUMAKRAS Phase 2 CodeBreaK 100 Clinical Trial

In a post-hoc analysis (WCLC21 Poster 52.03) of 40 patients (23% of 174 trial participants) with KRAS G12C-mutated advanced NSCLC who had stable, previously treated brain metastases at their enrollment in the CodeBreaK 100 trial, LUMAKRAS achieved a 77.5% disease control rate (DCR), a median progression-free survival (PFS) of 5.3 months and a median overall survival (OS) of 8.3 months. This DCR was similar to patients without brain metastases. In patients evaluable by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria, 14 of 16 patients (88%) maintained intracranial disease control of their stable brain lesions during LUMAKRAS therapy with two achieving complete responses of non-target lesions. The safety profile of LUMAKRAS in the brain metastases group was consistent with previous reports. Amgen is enrolling patients with active brain metastases in an arm of the CodeBreaK 101 study (NCT04185883).

"Up to 40% of patients with KRAS G12C-mutated NSCLC may develop brain metastases.1 Given the overall poor prognosis for this patient subset, there is an urgent need for novel treatment options,"2 said lead author Suresh S. Ramalingam, M.D., executive director of Winship Cancer Institute of Emory University in Atlanta. "Our results demonstrate the potential of sotorasib to provide meaningful clinical benefit for KRAS G12C-mutated NSCLC in the brain."

An additional exploratory descriptive analysis of CodeBreaK 100 being presented during a Mini Oral Presentation (MA14.03) examined whether the mutation profile of the tumors, in addition to KRASG12C, is correlated with patients' responses or resistance to LUMAKRAS. An analysis of baseline tumor samples from 65 patients revealed no single genetic signature that predicted LUMAKRAS responses and ongoing evaluations will be needed to further identify potential targetable mechanisms of resistance. However, the KEAP1 mutation, a known driver of poor clinical outcomes, was observed in 7 of 22 patients with early progression and PFS of less than 3 months.

"The introduction of sotorasib ushered in a new standard of care for patients with KRAS G12C-mutated NSCLC," said lead author Ferdinandos Skoulidis, M.D., Ph.D., assistant professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "These biomarker data provide direction for continued research into characterizing mutation profiles associated with sotorasib treatment response to help guide clinical practice and inform innovative combination approaches to overcome potential mechanisms of resistance."