Amgen Inc. announced the first combination study results from the Phase 1b/2 CodeBreaK 101 study, the most comprehensive global clinical development program in patients with KRAS G12C-mutated advanced colorectal cancer (CRC). These new data show that combining LUMAKRAS (sotorasib) with Vectibix (panitumumab), Amgen's monoclonal antibody epidermal growth factor receptor (EGFR) inhibitor, demonstrated encouraging efficacy and safety. Overall, the objective response rate (ORR) was 27% (confirmed and unconfirmed) among 26 patients in the efficacy analysis set (which included 5 patients who had progressed with prior sotorasib monotherapy). The disease control rate (DCR) was 81%. ORR and DCR were secondary endpoints. In the expansion cohort of sotorasib-naïve patients with refractory CRC (n=18), 33% of patients experienced a response (confirmed and unconfirmed). These data are being featured during the European Society of Medical Oncology 2021 (ESMO21) Virtual Congress. In total, 31 patients with heavily pretreated (median of two prior lines of therapy; range 1-10) KRAS G12C-mutated metastatic CRC were enrolled in the dose exploration and dose expansion cohorts for the combination of LUMAKRAS and Vectibix. No patients experienced dose-limiting toxicities during the 28 days following initial treatment. The majority of treatment-related adverse events (TRAEs) were Grade 1-2 in severity, and no Grade 4 or fatal TRAEs were observed. The most common TRAEs (occurring in > 10% of patients) were consistent with known adverse events for LUMAKRAS and Vectibix and included dermatitis acneiform, dry skin, nausea, diarrhea, hypokalemia, hypomagnesemia, pruritus and rash. No new safety concerns were identified. In addition to the LUMAKRAS combination research, a presentation will detail the design of an ongoing study of half-life extended (HLE) bispecific T cell engager (BiTE®) molecule tarlatamab with anti-PD-1 antibody AMG 404 in patients with small cell lung cancer. The multicenter, open-label, Phase 1b study will evaluate the safety and tolerability of the combination and determine dosing as primary objectives, as well as examine preliminary antitumor activity and pharmacokinetics as secondary objectives.