CoChat
Sign Up
Cited by 34Protein Degradation and InhibitorsPancreatic and Hepatic Oncology ResearchLung Cancer Treatments and Mutations

The DOI matches its Crossref record.

Trial in progress: A phase 1, first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of ASP3082 in patients with previously treated advanced solid tumors and KRAS G12D mutations.

Open access
Tolcher, Anthony W., Park, Wungki, Wang, Judy S., Spira, Alexander I., Janne, Pasi A., Lee, Ho-Jin, Gill, Stanley, LoRusso, Patricia, Herzberg, Benjamin, Goldman, Jonathan W., Morgensztern, Daniel, Berlin, Jordan, Kasi, Anup, Fujii, Hisaki, Pelster, Meredith·2023·Journal of Clinical Oncology
DOI 10.1200/jco.2023.41.4_suppl.tps764
Open this paper in CoChat — free accountOpen PDF

Abstract

TPS764 Background: Kirsten rat sarcoma (KRAS) G12D is a point mutation observed in various cancer types including pancreatic ductal cancer, colon adenocarcinoma, and lung cancers. ASP3082 is a novel small-molecule proteolysis-targeting chimeric degrader that binds to, and selectively targets, the KRAS G12D-mutated protein for degradation via recruitment of E3 ubiquitin ligase proteins. In preclinical studies, ASP3082 selectively degraded the KRAS G12D-mutated protein and showed growth inhibitory activity in KRAS G12D-mutated cancer cells but not in KRAS -wildtype cancer cells. Notable antitumor effects of ASP3082 have been demonstrated when intravenously administered weekly in mice xenografted with KRAS G12D-mutated cancer cells. Methods: This first-in-human, open-label, multicenter, phase 1 study evaluates the safety and tolerability of ASP3082 in patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer or other solid tumors. Participants with unresectable, locally advanced, or metastatic solid tumor malignancy with documented KRAS G12D mutation are eligible for enrollment. Part 1 consists of dose-escalation cohorts of 3−12 patients receiving intravenous administration of ASP3082 in a 21-day cycle. Part 2 consists of random assignment of ≤20 patients into 2 cohorts with different ASP3082 dose levels to determine the recommended phase 2 dose. Additional tumor-specific expansion cohorts may enroll ≤20 participants per tumor type. Primary endpoints will evaluate safety and tolerability as noted by dose-limiting toxicities, adverse events, serious adverse events, laboratory test results, electrocardiograms, vital signs, physical exams, and Eastern Cooperative Oncology Group performance status. Secondary endpoints will evaluate objective response rate, duration of response, disease control rate per Response Evaluation Criteria in Solid Tumors version 1.1, pharmacokinetics of single and repeated doses of ASP3082, and changes in KRAS G12D in tumor samples. Exploratory objectives will evaluate potential biomarkers that may correlate with treatment outcomes. Tumor assessment follow-up will continue for ≤45 weeks or until progressive disease. Enrollment in Cohort 1 is complete, and enrollment to Cohort 2 began in September 2022. Clinical trial information: NCT05382559 .

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1200/jco.2023.41.4_suppl.tps764

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Astellas is also investigating the use of ASP3082 in combination with the EGFR-blocking antibody cetuximab in Phase I trials, with encouraging results indicating the potential of combining EGFR blockers with KRASG12C inhibitors to control KRAS signaling.

    “Astellas is also investigating the use of ASP3082 in combination with the EGFR-blocking antibody cetuximab in Phase I trials, with encouraging results indicating the potential of combining EGFR blockers with KRASG12C inhibitors to control KRAS signaling (Fig. 5).485”

    From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [485]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Still being checked.

Cited by

Sorted by citations

Related

Metadata

Authors
Tolcher, A. W., Park, W., Wang, J. S., Spira, A. I., Janne, P. A., Lee, H.-J., Gill, S., LoRusso, P., Herzberg, B., Goldman, J. W., Morgensztern, D., Berlin, J., Kasi, A., Fujii, H., & Pelster, M.
Affiliations
  • NEXT Oncology, San Antonio, TX;
  • Memorial Sloan Kettering Cancer Center (US)
  • Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL;
  • Virginia Cancer Specialists (US)
  • Harvard University (US)
  • Astellas Pharma (United States) (US)
  • Yale University (US)
  • Herbert Irving Comprehensive Cancer Center (US)
  • University of California, Los Angeles (US)
  • Washington University in St. Louis (US)
  • Vanderbilt University (US)
  • University of Kansas Medical Center (US)
  • Sarah Cannon (US)
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2023-02-01
Volume
41
Issue
4_suppl
Pages
TPS764-TPS764
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2023.41.4_suppl.tps764
OpenAlex
W4317862701
Cited by
33
References
0
Citations by year
2026: 2 · 2025: 17 · 2024: 8 · 2023: 6
Type
conference abstract
Language
en
Open access
Locations
Journal of Clinical Oncology (publishedVersion)
Funders
Astellas
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
KRAS G12D mutation, advanced solid tumors, pancreatic cancer, colorectal cancer, non-small cell lung cancer, dose escalation, safety and tolerability, pharmacokinetics, objective response rate, biomarkers, E3 ubiquitin ligase, targeted cancer therapy, first-in-human

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review