Amgen Announces Phase Ib/II CodeBreaK 101 Data Showing 17.3% Higher Response Rate with Lumakras in Combination Therapy for KRAS G12C-Mutated Colorectal Cancer

Source: PharmaCube Info

Author: Shi Bei

On September 16, Amgen announced the first positive results from a combination therapy in the Phase Ib/II CodeBreaK 101 study for patients with advanced colorectal cancer (CRC) harboring KRAS G12C mutations. New data indicate that the combination of the KRAS G12C inhibitor Lumakras (sotorasib) and Amgen’s anti-EGFR monoclonal antibody Vectibix (panitumumab) demonstrates encouraging efficacy and safety. These findings support the initiation of a Phase III study evaluating Lumakras in combination with Vectibix for the third-line treatment of CRC.

The objective response rate (ORR) was 27% among the 26 patients included in the efficacy analysis set (including 5 patients who progressed after prior sotorasib monotherapy). The disease control rate (DCR) was 81%. In the expansion cohort of refractory CRC patients (n=18) who had not received prior sotorasib treatment, 33% achieved a response. These data will be presented at the 2021 ESMO Congress.

This dose-escalation and dose-expansion cohort study enrolled a total of 31 heavily pretreated patients with KRAS G12C-mutated metastatic CRC (median of 2 prior lines of therapy; range, 1–10). No patients experienced dose-limiting toxicity within 28 days of treatment initiation. The most common treatment-related adverse events (TRAEs) (occurring in >10% of patients) were consistent with the known adverse event profiles of Lumakras and Vectibix, including acneiform dermatitis, dry skin, nausea, diarrhea, hypokalemia, hypomagnesemia, pruritus, and rash. No new safety signals were identified.

In addition to reporting on Lumakras combination therapy studies, Amgen today also announced a collaboration with Boehringer Ingelheim (BI) to jointly explore the potential synergistic effects of combining Boehringer Ingelheim's SOS1::pan-KRAS inhibitor BI 1701963 with Lumakras.

BI 1701963 is an investigational oral small molecule that binds to the catalytic domain of SOS1, preventing its interaction with inactive KRAS, reducing the formation of active KRAS, and thereby inhibiting the MAPK signaling pathway in KRAS-dependent tumors. SOS1 inhibition also blocks feedback-mediated reactivation of the MAPK pathway. The SOS1: KRAS inhibitor demonstrates activity across a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins.

To date, Amgen has established the world's most comprehensive clinical development program targeting the KRAS G12C mutation.

Note: The original text has been abridged.