NEW YORK – The US Food and Drug Administration on Thursday approved Amgen's KRAS inhibitor Lumakras (sotorasib) with its EGFR monoclonal antibody Vectibix (panitumumab) for previously treated patients with KRAS G12C-mutated metastatic colorectal cancer.
The FDA simultaneously approved Qiagen's Therascreen KRAS RGQ PCR kit as a companion diagnostic to identify patients with KRAS G12C-mutant colorectal cancer who may be eligible for the treatment.
The approval was based on data from the Phase III CodeBreaK 300 study, in which researchers evaluated Lumakras-Vectibix against investigator's choice of standard-of-care treatment with Taiho Oncology's chemotherapy Lonsurf (trifluridine and tipiracil) or Bayer's VEGFR2-TIE2 inhibitor Stivarga (regorafenib) in this chemo-refractory patient population. The trial tested two dose levels of Lumakras and Vectibix, and the FDA approved the regimen at the higher dosage.
In CodeBreaK 300, the Lumakras-Vectibix combination improved response and survival outcomes compared to standard treatment. Median progression-free survival was 5.6 months on the higher dose of the Lumakras-Vectibix combo compared to 2.0 months in the control arm. About a quarter of the patients responded to Lumakras-Vectibix but none responded to the standard-of-care treatments. The median duration of response to Lumakras-Vectibix was 4.4 months.
"In metastatic colorectal cancer, KRAS mutations are historically associated with worse mortality rates and inferior outcomes compared to non-mutated tumors, and standard treatment options have shown minimal benefit," Marwan Fakih, primary study investigator and codirector of the Gastrointestinal Cancer Program at City of Hope, said in a statement. "Designed for dual blockade of KRAS G12C and EGFR pathways, the combination of sotorasib plus panitumumab provides a needed new treatment option to better overcome cancer's escape mechanisms."
Amgen is also exploring Lumakras with Vectibix and chemo as a first-line treatment in KRAS G12C-mutant metastatic colorectal cancer. Lumakras is also approved in the US as a treatment for previously treated, locally advanced, or metastatic KRAS G12C-mutant non-small cell lung cancer.