The KRAS Mutation: Cancer Patients Search for Hard-To-Find Trials

By Kathleen Hoffman, PhD, MSPH

There is new hope for cancer patients with the mutated protein KRAS G12C, an oncogene previously thought to be “undruggable.”¹ KRAS is one part of the RAS-RAF cellular signaling pathway that drives a cell to multiply, and its mutations are commonly present in pancreatic, colorectal, and non-small cell lung cancers (NSCLC), all of which have a poor prognosis.²

In 2013, the NIH National Cancer Institute founded the RAS Initiative for exploring approaches for attacking the proteins encoded by mutant forms of RAS genes, including KRAS.³  It has been a decades-long challenge to find an inhibitor that targets only mutated forms of this ubiquitous protein and effectively binds with its unusually smooth surface.¹

[My son’s] oncologist did a DNA testing on his tumor, everyone should have this done, and it found that he has the Wild Type KRAS gene… that will make his cancer (it’s aggressive) split, grow and go wild.

That same year, a binding pocket was identified in a mutation called KRAS G12C. This particular variant is present in 14% of NSCLC cases, amounting to 14,000 people in the US per year.⁴ Several immunotherapy drugs are finally reaching the clinical trial stage, which opens a door to patients who previously had few options.^1,4,5

My mom recently started the [treatment] trial to target her lung cancer since she has the KRAZ12gc mutation. She has already done chemo and radiation. She finally fell in the category for this trial.

However, that “door” — phase 3 clinical trials or trials in pre-recruitment for a genetic variant — has been hard for patients themselves to find. That’s what Tom Marsilje, Ph.D., discovered when he, as both a cancer scientist and a patient with aggressive colorectal cancer, tried using clinical trials.gov to find the trials for which he was eligible. [See our previous Patient Pulse blog, “Hacking Clinical Trials,” for more background.] If a cancer scientist found it challenging, how were patients, already dealing with a diagnosis, supposed to find them?

Believe it is time to start considering and watching for any Clinical trials that may come available [for stage IV NSCLC] especially if next scan is not good. willing to travel within US. Thanks for any help you can offer

This led Marsilje to develop a patient-curated app in 2017 for finding applicable colorectal cancer trials, an app still available to this day on the Fight Colorectal Cancer website. (Fight Colorectal Cancer is an Inspire community partner. The app’s technology is diagnosis-independent and available to other groups.)

The app exemplifies one of the many ways patients and patient advocacy groups are lowering the barriers to clinical trial enrollment. On Inspire, patients are already educating each other about finding applicable treatments and clinical trials for their individual cancer variants.

I am on the fifth day of the clinical trial [treatment] due to having the KRAS 12gc mutation… If interested in a [treatment] trial but none are near you, then look up trials for [other treatment] which is similar and has had good results.

There have already been over 4,700 posts and 4,100 searches on Inspire on KRAS. This reflects a well-informed group of patients who are already aware that their cancers are affected by a genetic mutation. These members are spreading the word to other people looking for a cure. If scientists are trying to find people to participate in phase 3 pre-launch clinical trials, here is an audience of people actively looking for trials to join.

Inspire’s members with cancers are also open to participating in research to enhance the development of protocol design as well as epidemiological, and outcomes research. To learn more, take a look at Inspire’s case studies which describe partnerships with clinical and marketing researchers to obtain information on patient (and caregiver) knowledge, understanding, medical history, and/or unmet needs.