sotorasib and Colorectal-Neoplasms

In this phase 3, multicenter, open-label, randomized trial, we assigned patients with chemorefractory metastatic colorectal cancer with mutated. After a median follow-up of 7.8 months (range, 0.1 to 13.9), the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 6.3) and 3.9 months (95% CI, 3.7 to 5.8) in the 960-mg sotorasib-panitumumab and 240-mg sotorasib-panitumumab groups, respectively, as compared with 2.2 months (95% CI, 1.9 to 3.9) in the standard-care group. The hazard ratio for disease progression or death in the 960-mg sotorasib-panitumumab group as compared with the standard-care group was 0.49 (95% CI, 0.30 to 0.80; P = 0.006), and the hazard ratio in the 240-mg sotorasib-panitumumab group was 0.58 (95% CI, 0.36 to 0.93; P = 0.03). Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0% (95% CI, 0.0 to 6.6) in the 960-mg sotorasib-panitumumab, 240-mg sotorasib-panitumumab, and standard-care groups, respectively. Treatment-related adverse events of grade 3 or higher occurred in 35.8%, 30.2%, and 43.1% of patients, respectively. Skin-related toxic effects and hypomagnesemia were the most common adverse events observed with sotorasib-panitumumab.. In this phase 3 trial of a KRAS G12C inhibitor plus an EGFR inhibitor in patients with chemorefractory metastatic colorectal cancer, both doses of sotorasib in combination with panitumumab resulted in longer progression-free survival than standard treatment. Toxic effects were as expected for either agent alone and resulted in few discontinuations of treatment. (Funded by Amgen; CodeBreaK 300 ClinicalTrials.gov number, NCT05198934.).

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; ErbB Receptors; Humans; Mutation; Panitumumab; Proto-Oncogene Proteins p21(ras)

Sotorasib, a specific, irreversible KRAS. In this single-arm, phase 2 trial, adult patients with KRAS. On March 1, 2021, at data cutoff, 62 patients with KRAS. Although the 9·7% overall response rate did not reach the benchmark, oral administration of sotorasib once per day showed modest anti-tumour activity and manageable safety in these heavily pretreated chemorefractory patients. Sotorasib is under evaluation in combination with other therapeutics to increase potential activity and overcome potential resistance mechanisms.. Amgen.

Topics: Adult; Aged; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Mutation; Piperazines; Proto-Oncogene Proteins p21(ras); Pyridines; Pyrimidines

No therapies for targeting. We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the. A total of 129 patients (59 with NSCLC, 42 with colorectal cancer, and 28 with other tumors) were included in dose escalation and expansion cohorts. Patients had received a median of 3 (range, 0 to 11) previous lines of anticancer therapies for metastatic disease. No dose-limiting toxic effects or treatment-related deaths were observed. A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma.. Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasms; Piperazines; Proto-Oncogene Proteins p21(ras); Pyridines; Pyrimidines

The KRAS inhibitor sotorasib provides some clinical benefit in patients with advanced or metastatic KRASG12C-mutant colorectal cancer, according to results of a phase II clinical trial. The objective response rate was 9.7%, the disease control rate was 82.3%, and the progression-free survival was 4 months.

Topics: Antineoplastic Agents; Colorectal Neoplasms; Humans; Mutation; Piperazines; Pyridines; Pyrimidines

Topics: Colorectal Neoplasms; Humans; Lung Neoplasms; Piperazines; Proto-Oncogene Proteins p21(ras); Pyridines; Pyrimidines

Most patients with

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cetuximab; Colorectal Neoplasms; Drug Resistance, Neoplasm; ErbB Receptors; Female; Humans; Mice, SCID; Piperazines; Protein Kinase Inhibitors; Proto-Oncogene Proteins p21(ras); Pyridines; Pyrimidines

The latest results from the CodeBreak 100 trial evaluating AMG 510 indicate that this first-in-class KRAS inhibitor, having shown promise in non-small cell lung cancer, is modestly active in several other types of solid tumors, including colorectal cancer.

Topics: Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; ErbB Receptors; Humans; Lung Neoplasms; Piperazines; Pyridines; Pyrimidines