The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Sotorasib, a KRASG12C inhibitor, demonstrated a favorable safety profile and antitumor activity among patients with advanced non-small cell lung cancer (NSCLC), according to results of a phase 1 study presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“Despite the discovery of the KRAS oncogene almost 4 decades ago, there is currently no approved therapy targeting KRAS,” said David S. Hong, of The University of Texas MD Anderson Cancer Center, Houston. The KRAS p.G12C mutation is present in approximately 13% of NSCLCs.

The multicenter, open-label, phase 1 CodeBreaK 100 trial ( Identifier: NCT03600883) included 129 patients with KRASG12C mutations, including 59 patients with previously treated advanced NSCLC. All patients were treated with 180 mg to 960 mg of oral sotorasib (AMG 510) once daily until disease progression. Interpatient dose escalation was allowed. Approximately 20 patients were then enrolled in a dose expansion study with long-term follow-up.

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The primary endpoint was safety and secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS). Biomarkers were also evaluated, including the mutant allele frequency of KRAS p.G12C mutation, PD-L1 expression levels, and tumor mutational burden (TMB).

Data were presented for the NSCLC cohort. At baseline, the median age was 68 years and 56% of patients were female. Most patients (95%) received at least 1 prior line of therapy. Brain metastases were present among 33% of patients.

During a median follow-up of 11.7 months, the ORR was 32.2% and the DCR was 88.1%, which was higher among patients treated with the 960 mg dose at 35.3% and 91.2%, respectively.

The median time to response was 1.4 months and the median DOR was 10.9 months (range, 1.1+ to 13.6 months). The median PFS was 6.3 months.

Response to sotorasib was not associated with KRAS p.G12C allele frequency, PD-L1 expression levels, or TMB. “Sotorasib demonstrated clinical activity across a range of tissue comutation profiles,” Dr Hong said.

Grade 3 to 4 treatment-related adverse events (TRAEs) occurred among 20.3% of patients and led to 1 patient discontinuing treatment. The most common grade 3 to 4 TRAEs included elevation of alanine aminotransferase elevation or aspartate aminotransferase elevation, and diarrhea. There were no dose-limiting toxicities or fatal TRAEs.

“Sotorasib monotherapy, overall, demonstrated a very favorable safety profile,” Dr Hong said.

Dr Hong concluded that “sotorasib demonstrated durable disease control in heavily pretreated patients with NSCLC.” The 960 mg dose was selected for subsequent testing in NSCLC.

Disclosures: Multiple authors declared affiliation with industry. Please refer to the original abstract for a full list of disclosures.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.


Hong DS, Bang Y-J, Barlesi F, et al. Durability of clinical benefit and biomarkers in patients with advanced non-small lung cancer (NSCLC) treated with aMG 510 (sotorasib): CodeBreaK 100. Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract 1257O.