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Cited by 45Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsProtein Kinase Regulation and GTPase Signaling

First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: A phase I/II study evaluating efficacy and safety

Strickler, John H, Satake, Hironaga, Hollebecque, Antoine, Sunakawa, Yu, Tomasini, Pascale, Bajor, David Lawrence, Schuler, Martin H., Yaeger, Rona +12 more·2022·Journal of Clinical Oncology
DOI 10.1200/jco.2022.40.36_suppl.360490
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Abstract

360490 Background: KRAS mutation is present in 90% of pancreatic ductal adenocarcinomas with p.G12C accounting for 1% to 2% of these mutations. Sotorasib, a small molecule that specifically and irreversibly inhibits KRAS G12C, has been investigated in the CodeBreaK100 trial in patients with KRAS G12C-mutated advanced solid tumors. Herein, we report on the largest dataset evaluating efficacy and safety of a KRAS G12C inhibitor in patients with pretreated KRAS G12C-mutated pancreatic cancer. Methods: CodeBreaK100 (NCT03600883) is an international, single arm, phase I/II study evaluating the efficacy and safety of sotorasib in patients with KRAS G12C-mutated advanced solid tumors with ≥ 1 prior systemic therapy unless intolerant or ineligible for available therapies. The primary efficacy endpoint is confirmed objective response rate (ORR), assessed by blinded independent central review (BICR) per RECIST 1.1. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: As of November 1, 2021, 38 patients with pancreatic cancer (mean age: 65 years, 76.3% male) from the combined phase I/II study received sotorasib 960 mg once daily. Stage IV disease was present in 55.3% of patients at diagnosis, and in all patients at enrollment. Baseline ECOG scores were 0, 1, or 2 in 31.6%, 57.9%, and 10.5% of patients, respectively. Most patients (79%) had ≥ 2 prior lines of therapy (median: 2 [range: 1-8]). Median treatment duration was 4.1 months with a median follow-up of 16.8 months. Eight patients had confirmed partial response by BICR with a resulting ORR of 21.1% (95% CI: 9.55%-37.32%). DCR was 84.2% (Table 1). Treatment-related adverse events (TRAEs) of any grade occurred in 16 (42.1%) patients. Grade ≥ 3 TRAEs occurred in 6 patients: diarrhea (2); fatigue (2); abdominal pain, ALT increase, AST increase, pleural effusion, and pulmonary embolism (1 each). No TRAEs were fatal or resulted in sotorasib discontinuation. Conclusions: Sotorasib demonstrated clinically meaningful anticancer activity and tolerability in patients with heavily pretreated KRAS G12C-mutated advanced pancreatic cancer, who have limited treatment options and poor prognosis. Clinical trial information: NCT03600883. [Table: see text]

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  • In CodeBreaK 100, the PDAC cohort had an ORR of 21.1% and DCR of 84.2% in 38 heavily pretreated patients, whereas the CRC cohort of 62 patients had an ORR of 9.7%.

    “data from the PDAC cohort of CodeBreaK 100 showed an ORR of 21.1% and a DCR of 84.2% in a heavily pretreated patient population (n = 38)78. However, similar success was not seen in the CRC cohort (n = 62), in which the ORR was 9.7%79.”

    From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [78]

  • In 38 patients with pancreatic cancer, sotorasib led to an ORR of 21.1% and DCR of 84.2%.

    “In 38 patients with pancreatic cancer, sotorasib led to an ORR of 21.1% and DCR of 84.2% [98].”

    From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [98]

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Authors
Strickler, J. H., Satake, H., Hollebecque, A., Sunakawa, Y., Tomasini, P., Bajor, D. L., Schuler, M. H., Yaeger, R., George, T. J., Garrido-Laguna, I., Coveler, A. L., Vincent, M. D., Falchook, G. S., Burns, T. F., Rha, S. Y., Lemech, C. R., Juric, D., Jafarinasabian, P., Tran, Q., & Hong, D. S.
Affiliations
  • Duke Medical Center (US)
  • Kobe City Medical Center General Hospital (JP)
  • Institut Gustave Roussy (FR)
  • St. Marianna University School of Medicine (JP)
  • Aix-Marseille Université (FR)
  • University Hospitals Seidman Cancer Center (US)
  • West German Cancer Center, Essen, Germany;
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Florida (US)
  • Huntsman Cancer Institute, University of Utah, Salt Lake City, UT;
  • Seattle Cancer Care Alliance (US)
  • London Health Sciences Centre (CA)
  • Sarah Cannon Research Institute, Denver, CO;
  • UPMC Hillman Cancer Center (US)
  • Yonsei University (KR)
  • Scientia Clinical Research, Randwick, Australia;
  • Harvard University (US)
  • Amgen (United States) (US)
  • The University of Texas MD Anderson Cancer Center (US)
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2022-04-20
Volume
40
Issue
36_suppl
Pages
360490-360490
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2022.40.36_suppl.360490
OpenAlex
W4212858891
Cited by
45
References
0
Citations by year
2026: 2 · 2025: 5 · 2024: 7 · 2023: 15 · 2022: 16
Type
conference abstract
Language
en
Open access
closed
Locations
Journal of Clinical Oncology (publishedVersion)
Funders
Amgen Inc.
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
sotorasib, KRAS G12C mutation, pancreatic ductal adenocarcinoma, KRAS inhibitors, objective response rate, treatment-related adverse events, drug safety, progression-free survival, overall survival, duration of response, disease control rate, targeted therapy

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