KEY TAKEAWAYS
- The CodeBreaK 100 phase 2 study showed that Sotorasib, a KRAS G12C inhibitor, had a modest clinical activity as monotherapy in heavily pretreated patients with KRAS G12C-mutated colorectal cancer, with an ORR of 9.7%.
- The dose expansion cohort of 40 patients with refractory mCRC showed a confirmed ORR of 30% and a disease control rate of 90% when treated with Soto and Pmab.
- TRAEs of any grade occurred in 37 (92.5%) patients, with no TRAEs resulting in treatment discontinuation, and safety findings were consistent with known profiles of Soto and Pmab.
- The radiographic response rate using Response Evaluation Criteria in Solid Excrescences 1.1 was also 57.
- Soto and Pmab in heavily pretreated patients with KRAS G12C-mutated mCRC, supporting further development of this combination.
In the CodeBreaK 100 phase 2 study, sotorasib (Soto), a KRAS G12C inhibitor, had modest clinical activity as monotherapy in patients (pts) with KRAS G12C -mutated colorectal cancer (CRC), with an objective response rate of 9.7% (ORR). Soto, in combination with panitumumab (Pmab), an EGFR antibody, demonstrated encouraging anticancer efficacy in chemorefractory KRAS G12C -mutated metastatic CRC in the CodeBreaK 101 phase 1b dosage exploration (n=8) and expansion (n=18) cohorts (mCRC). The data from the dose expansion cohort of 40 patients with refractory mCRC are presented here.
Dose-finding and dose-expansion studies across different cohorts are a part of subprotocol H of CodeBreaK 101 (NCT04185883). Progression on or after prior fluoropyrimidine, oxaliplatin, irinotecan, and an anti-angiogenic drug were essential inclusion criteria for the refractory mCRC cohort. Safety is the primary metric. Secondary objectives include antitumor efficacy, progression-free survival (PFS), overall survival (OS), and pharmacokinetics.
Around 40 patients (75% women, median age 57.5 years) had been enrolled as of March 25, 2022, and all received Soto 960 mg orally twice a day and Pmab 6 mg/kg intravenously every 2 weeks.
The specific number of previous treatments was 2. Most patients (37, or 92.5%) experienced treatment-related adverse events (TRAEs) of some severity. About 9 (22.5%) pts experienced TRAEs of grade 3, with 6 (15%) of those being Soto-related and 8 (20%) being Pmab-related. There were no serious adverse events during treatment (TRAEs), and no patients had to stop using the drug because of side effects. The data on safety was in line with what was already known about Soto and Pmab. The ORR was verified to be 30% (95% CI, 16.6-46.5). The disease prevention and control rate was 90% (95% CI, 76.3 to 97.2). In 35 (87.5%) patients, tumor reduction of some size was seen.
The pharmacokinetic (PK) exposures in the Soto study were similar to those in monotherapy studies. This dataset provides further evidence of safety and tolerability for Soto and Pmab in extensively pretreated pts with KRAS G12C-mutated mCRC, with 3-fold more significant response than previously found with Soto monotherapy, supporting further development of this combination. Extended follow-up data with the duration of response, PFS, and OS will be reported.
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT04185883
Y. Kuboki, R. Yaeger, M. Fakih, J.H. Strickler, T. Masuishi, E.J. Kim, C.M. Bestvina, C.J. Langer, J.C. Krauss, S. Puri, P. Cardona, E.K. Chang, Q. Tran, D.S. Hong. 2022. 45MO – Sotorasib in combination with panitumumab in refractory KRAS G12C-mutated colorectal cancer: Safety and efficacy for phase Ib full expansion cohort. Annals of Oncology (2022) 33 (suppl_9): S1445-S1453. 10.1016/annonc/annonc1122
