Amgen (NASDAQ:AMGN) today announced data from the global Phase 3 CodeBreaK 300 trial evaluating two doses of LUMAKRAS^® (sotorasib) (960 mg or 240 mg) in combination with Vectibix^® (panitumumab). Both doses demonstrated a statistically significant superiority in progression-free survival (PFS) over the investigator’s choice of therapy in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC). The results are being presented today at the Presidential Symposium 2 session as a late-breaking oral presentation (LBA10) during the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain, with simultaneous publication in the New England Journal of Medicine.

“The CodeBreaK 300 trial demonstrated the benefit of LUMAKRAS plus Vectibix to deliver statistically significant PFS outcomes for patients compared to the investigator’s choice of therapy, offering new hope to this population with historically poor outcomes,” said David M. Reese, M.D., executive vice president, Research and Development at Amgen.

After a median follow-up of 7.8 months, the median PFS was 5.6 months and 3.9 months with LUMAKRAS 960 mg plus Vectibix and LUMAKRAS 240 mg plus Vectibix respectively, versus 2.2 months with investigator’s choice of therapy (trifluridine and tipiracil, or regorafenib). The improvement in PFS for patients treated with LUMAKRAS plus Vectibix was seen across key subgroups, including tumor sidedness, primary tumor location, prior lines of therapy and presence or absence of liver metastases. Among secondary endpoints, higher objective response rate (ORR) and disease control rate (DCR) were observed in patients treated with LUMAKRAS plus Vectibix at both doses versus investigator’s choice of care. Patients at both dose regimens of LUMAKRAS plus Vectibix experienced a longer duration of treatment than those treated with investigator’s choice therapy.

“With these new data, sotorasib plus panitumumab showed consistent efficacy across key subgroups at both doses and supports the biologic rationale of combining these two biomarker-directed therapies,” said Filippo Pietrantonio, M.D., Fondazione IRCCS Istituto Nazionale dei Tumori. “Fewer than 20% of people diagnosed with mCRC survive beyond five years, and additional treatment options are clearly needed, particularly for the patients with KRAS mutations for whom evidence-based targeted options were not yet available.” 

The most common Grade ≥3 treatment-related adverse events (TRAEs) with LUMAKRAS plus Vectibix were dermatitis acneiform (960 mg: 11%; 240 mg: 4%), hypomagnesemia (960 mg: 6%; 240 mg: 8%), rash (960 mg: 6%; 240 mg: 2%), and diarrhea (960 mg: 4%; 240 mg: 6%).

Based on the CodeBreaK 300 primary analysis results, Amgen is planning to submit these data to regulatory authorities.