Amgen announced the new data from the CodeBreaK clinical trial program, which it notes is the most comprehensive of global development program in patients with KRAS G12C-mutated cancers. The announcement was made at the American Society of Clinical Oncology (ASCO) annual meeting held from June 2-6 in Chicago.
They also presented data today (June 6) from Scarlet – an Amgen funded investigator study sponsored by the West Japan Oncology Group, which is the first study to highlight the safety and efficacy of sotorasib in combination with platinum-based chemotherapy for frontline treatment of patients with advanced NSCLC who have a KRAS G12C mutation.
Executive vice president of research and development at Amgen, David Reese, said: “As the leader in KRAS inhibition, Amgen continues to advance the CodeBreaK program by evaluating LUMAKRAS across different indications and combinations to potentially help more people living with KRAS G12C-mutated cancers.
“These data presented at ASCO underscore the clinical importance of Lumakras, including the only randomized trial of a KRAS G12C inhibitor to show higher intracranial activity compared to chemotherapy, along with data validating our combination treatment approach in metastatic colorectal cancer, where new precision medicine strategies are desperately needed.”
Improved CNS activity in advanced NSCLC
The phase 3 CodeBreaK 200 trial, the first and only randomized study for any KRAS G12C inhibitor, included patients with advanced NSCLC and a treated or stable central nervous system (CNS) lesions at baseline as assessed by a blinded independent central review (BICR).
In this analysis using a modified exploratory response assessment in neuro-oncology brain metastases (RANO-BM), Lumakras demonstrated delayed time to CNS progression and longer CNS progression-free survival (PFS) compared with docetaxel, an antineoplastic agent used in the management of multiple metastatic and non-resectable tumor types.
Additionally, the company said, the CNS objective response rate (ORR), an assessment of CNS tumor shrinkage following treatment, was more than double (33.3% vs 15.4%) in 18 patients treated with Lumakras compared to docetaxel 13 patients. The safety profile in this analysis was similar to the CodeBreaK 200 overall population.
Melissa Johnson is director of Lung Cancer Research at the Sarah Cannon Research Institute at Tennessee Oncology. She said: “CNS metastases are an unfortunately common complication of KRAS G12C-mutated advanced NSCLC, occurring in about 30–40% of patients.
“In this post-hoc analysis from CodeBreaK 200, sotorasib delayed CNS progression-free survival by more than five months and is a potential clinically meaningful benefit for second-line NSCLC patients with KRAS G12C mutations.”
Consistent Clinical Benefit Across Subgroups
In the first randomized, molecularly defined analysis of a KRASG12C inhibitor versus chemotherapy, Lumakras showed improved progression free survival (PFS) over docetaxel, irrespective of PD-L1 expression level. The PD-L1 adaptive expression is a consequence of the presence of tumor antigen–specific T cells that recognized the cancer cells leading to the production of interferon-γ. The analysis also showed retained PFS benefit versus docetaxel across key co-alteration subgroups. Collectively, the biomarker data help inform treatment decision making and the ongoing CodeBreaK clinical development program, which explores Lumakras in novel combinations.
Encouraging Safety and Efficacy in Metastatic CRC
Data from the CodeBreaK 101 Phase 1b study, the first reported results for the combination of Lumakras with Vectibix (panitumumab) and Folfiri, showed encouraging safety and efficacy in previously-treated KRAS G12C-mutated metastatic CRC.
Among 42 patients evaluable for response, confirmed ORR was 55% and disease control rate (DCR) was 93%, with responses observed regardless of the number of prior lines of therapy and regardless of progression on prior irinotecan-based therapy. Lumakras plus Vectibix and Folfiri combination reported adverse events consistent with those expected for the therapies under study.
David Hong is professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, Houston.
He said: “A priority in KRAS G12C-mutated colorectal cancer research is exploring new treatment combinations that can drastically improve response rates attained with current treatments, which can be as low as 2%,” said lead investigator, David S. Hong, M.D., “These results showed encouraging efficacy with sotorasib in combination with panitumumab and FOLFIRI, and importantly showed consistent safety for each product.”