Targeting a KRAS Variant in Advanced Pancreatic Cancer

Eric Snyder; National Cancer InstituteHuntsman Cancer Institute at the Univ. of Utah

KRAS is one of the most frequently mutated oncogenes in various cancers.

A KRAS mutation is found in 95 percent of pancreatic cancers and KRAS G12D is one of the most common variants, occurring in approximately 34 percent of patients. The mutation causes hyperactivity of the pathways that lead to abnormal cancer cell growth, invasion, and metastasis.

Despite being the subject of extensive research, therapies targeting KRAS G12D remain elusive due to a lack of drug-binding pockets on the protein. Scientists are testing a new targeted protein degradation (TPD) approach for solid tumors, as a way to eliminate KRAS G12D and block its ability to send signals that turn on cancer cells and cause them to grow and spread.

What Is ASP3082?

ASP3082 is a protein degrader that acts as a link by binding specifically to KRAS G12D and at the same time to the protein degradation machinery, which being linked/in close proximity to KRAS G12D can tag it for degradation stopping its activities. The purpose of this phase I study is to evaluate the safety and tolerability of the investigational drug ASP3082 in people with inoperable or metastatic solid tumors that contain the KRAS G12D mutation.

The first part of the study consists in treating different groups of patients with different doses to define the optimal dose. In part two of the study, patients will be enrolled in different groups to receive ASP3082 alone (at the dose defined in part one); together with cetuximab, a drug sometimes used to treat KRAS cancers; or with chemotherapy.

Researchers will be evaluating safety and tolerability as the primary endpoints, as well as objective response rate, duration of response, disease control rate, and certain pharmacokinetic indicators to assess how the drug is working in the body. They will also explore potential biomarkers that may correlate with treatment outcomes.

How to Participate

To be eligible for this study, patients must have a solid tumor that is locally advanced or metastatic and has a KRAS G12D mutation. Their tumor must be able to be biopsied safely during the study, and at least three weeks must pass since the completion of prior anticancer treatment. Patients who meet the qualification criteria but have never received treatment may also participate in the chemotherapy and ADP3082 cohorts.  

We encourage you to consult your physicians for clinical trials that may be right for you. The website ClinicalTrials.gov provides more details about this trial as well as many others. You can visit the Let’s Win Trial Finder for a list of all active pancreatic cancer clinical trials.

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