Benzinga | Oct 7, 2021 09:05AM EDT

Amgen Reports LUMAKRAS Combed Data From Phase 1b CodeBreaK 101 Study In Patients With KRAS G12C-mutated Cancers At AACR-NCI-EORTC 2021 Conference

Amgen (NASDAQ:AMGN) today announced new combination study results from the Phase 1b CodeBreaK 101 study, a comprehensive global master protocol trial evaluating the safety and efficacy of LUMAKRAS(tm) (sotorasib), the first and only approved KRASG12C inhibitor, in more than 10 different investigational combination regimens for the treatment of patients with KRAS G12C-mutated cancers. Results from two arms of the study -- LUMAKRAS with afatinib, a pan-ErbB tyrosine kinase inhibitor, and LUMAKRAS with trametinib, a mitogen-activated protein kinase inhibitor (MEKi) -- will be presented at the plenary session titled 'Drugging Difficult Targets' during the AACR-NCI-EORTC 2021 Virtual International Conference on Molecular Targets and Cancer Therapeutics on Saturday, Oct. 9, 2021.

"A critical component of cancer drug development is to interrogate multiple pathways to understand whether different combinations can meaningfully advance cancer care. For this reason, Amgen has undertaken the broadest and most comprehensive global clinical development program for patients with the KRAS G12C mutation, exploring multiple combinations that will allow us to understand where we can best serve patients," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Consistent with our master protocol clinical trial design, which allows us to rapidly add, expand or remove cohorts to quickly understand what combinations work best for patients, Amgen will take these afatinib and trametinib results into account as we prioritize which combinations to move forward within our comprehensive LUMAKRAS development program. We look forward to presenting additional data, including PD-1 and SHP2 combination datasets, in the coming months."

LUMAKRAS in Combination with Afatinib (Abstract LBA6581)

The LUMAKRAS and afatinib combination arm enrolled 33 heavily pre-treated patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC), including five patients previously treated with LUMAKRAS monotherapy. Ten patients received 20 mg of afatinib/960 mg of sotorasib (cohort 1; 4 patients with prior LUMAKRAS experience) and 23 patients received 30 mg of afatinib/960 mg of sotorasib (cohort 2; 1 patient with prior LUMAKRAS experience). The objective response rate (ORR) was 20% in cohort 1 and 35% in cohort 2, and the disease control rate was 70% and 74% in the two cohorts, respectively.

The most common treatment-related adverse events (TRAEs) for this study were diarrhea, nausea, and vomiting. TRAEs of grade 3 occurred in 30% of patients in both dose groups with diarrhea being the most common.

LUMAKRAS in Combination with Trametinib (Abstract LBA6580)

In CodeBreaK 101, the combination of LUMAKRAS and trametinib showed antitumor activity in heavily pre-treated patients with KRAS G12C-mutated solid tumors, including those with prior KRASG12C inhibitor treatment. A total of 41 patients were enrolled in the Phase 1b study with 18 patients with NSCLC, 18 patients with colorectal cancer (CRC) and five patients with other solid tumors. The maximum tolerated dose tested was 2 mg trametinib/960 mg sotorasib administered daily.

In patients with CRC who were KRASG12C inhibitor na?ve, 9% achieved partial response (1 of 11), and 82% achieved disease control (9 of 11). In patients who were previously treated with a KRASG12C inhibitor, 14% achieved partial response (1 of 7), and 86% achieved disease control (6 of 7).

In patients with NSCLC who were KRASG12C inhibitor na?ve, 20% achieved partial response (3 of 15) and 87% achieved disease control (13 of 15). In patients who were previously treated with a KRASG12C inhibitor, 67% achieved disease control (2 of 3).

The most common TRAEs for this study were diarrhea, rash, dermatitis acneiform, nausea and vomiting. No new safety concerns were identified.