Sotorasib has demonstrated “meaningful anticancer activity” in pretreated patients with KRASG12C-mutated, advanced pancreatic cancer, according to an American Society of Clinical Oncology (ASCO) Plenary Series presentation. 

These results, from the phase 1/2 CodeBreak 100 trial, were presented by John H. Strickler, MD, of Duke University Medical Center in Durham, North Carolina. 

The ongoing CodeBreak 100 trial (ClinicalTrials.gov Identifier: NCT03600883) is enrolling patients with KRASG12C-mutated, advanced solid tumors. The current analysis includes only patients with advanced pancreatic cancer who had received 1 or more prior systemic therapies.


Continue Reading

Dr Strickler presented results in 38 patients, 12 who were enrolled in the phase 1 dose-escalation portion of the study and 26 who were enrolled in the phase 2 portion. All 38 patients received sotorasib at 960 mg once daily.

The median age of the patients was 65.5 years (range, 45-81 years). Most patients were men (76.3%), and most had an Eastern Cooperative Oncology Group performance status of 0 (31.6%) or 1 (57.9%). All patients had stage IV disease at enrollment, and 55.3% had stage IV disease at diagnosis. The median number of prior therapies was 2 (range, 1-8), and 78.9% of patients had received at least 2 prior treatments.

Results

The median duration of sotorasib treatment was 4.1 months. The objective response rate was 21.1%, with all 8 responders having a partial response. The disease control rate was 84.2%.  

The median duration of response was 5.7 months. At a median follow-up of 16.8 months, the median progression-free survival was 4.0 months, and the median overall survival was 6.9 months. 

Dr Strickler highlighted the outcome of 1 patient in particular, a 64-year-old woman who was diagnosed with stage IV disease. The patient had a 42% reduction in tumor volume with sotorasib treatment. The target lesion, which had measured 2.2 cm at baseline, had decreased to 0.8 cm at 18 weeks. 

The median time to response for this patient was 1.3 months, and the median duration of response was 5.8 months. The patient had no treatment-related adverse events (TRAEs). Unfortunately, she withdrew from the study after moving and died shortly after discontinuing treatment, Dr Strickler said.

For the entire cohort, the incidence of TRAEs was 42.1%. Grade 3 TRAEs included diarrhea (5.3%), fatigue (5.3%), abdominal pain (2.6%), alanine aminotransferase increase (2.6%), aspartate aminotransferase increase (2.6%), pleural effusion (2.6%), and pulmonary embolism (2.6%). 

There were no grade 4 or 5 TRAEs, and none of the TRAEs led to discontinuation of sotorasib. 

Sotorasib demonstrated “meaningful anticancer activity” and was well tolerated in this patient population, Dr Strickler said in closing.

“This is the largest dataset so far evaluating a KRASG12C inhibitor in heavily pretreated KRASG12C-mutated pancreatic cancer with a resulting centrally confirmed objective response rate of 21% and a disease control rate of 84%,” Dr Strickler said. “These data support further exploration of sotorasib in this patient population with high unmet medical need.” 

Disclosures: This research was supported by Amgen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Strickler JH, Satake H, Hollebecque A, et al. First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: A phase I/II study evaluating efficacy and safety. ASCO Plenary Series; February 15, 2022. Abstract 360490.