First patient on clinical trial thankful for UT MD Anderson

When Cindy Mette first received a colorectal cancer diagnosis from her doctor in Las Vegas, she never imagined that doctors halfway across the country would be comparing her to John Glenn. At the time, all she felt was disbelief.

She had noticed a drop in her energy, which led doctors to perform a colonoscopy in early 2022. Her doctors found and were later able to remove a colon tumor.

But less than a year after surgery, the cancer had come back and spread. In 2023, her doctors told her she had stage 4 colorectal cancer and had “months, not years” to live. He recommended she enroll on an immunotherapy clinical trial being run in Las Vegas.

“I remember thinking, ‘This can’t be how it ends.’ I wanted more time with my children, grandchildren and great-grandchildren,” Cindy recalls. “My husband and I were a couple of years from celebrating our 50^th anniversary. I had to be there for that!”

Finding hope in Houston

A friend recommended that she check out UT MD Anderson, and in April 2023, Cindy and her husband, Dennis, made the first of what would be many trips to Houston. In July, they first met with colon cancer specialist Scott Kopetz, M.D., Ph.D., who agreed with the recommendation for the clinical trial back in Las Vegas.

But he also said something that Cindy hadn’t heard from any of the doctors she’d met with. “I remember him saying, ‘We can cure this,’” she recalls. “And that was just a huge weight being lifted. Now, we had hope.”

Within a few months, she had to discontinue the clinical trial because the cancer continued to progress. Her doctors told her at that point that her best option was chemotherapy, which she had already decided she didn’t want to start unless it was the only option.

Cindy conferred again with Kopetz, who provided another option.

She joined a clinical trial for a fecal transplant therapy to see if modifying her gut microbiome would cause the tumors to respond to immunotherapy. That approach also failed.

“At that point, Dr. Kopetz said there was another option if I was ready to fight, and I told him I was. He wanted to introduce us to a ‘brilliant scientist’ who might have another option,” she recalls.

Becoming patient 00001

In January 2024, the Mettes flew back to Houston to meet with medical oncologist Timothy Yap, M.B.B.S., Ph.D., who was enrolling patients for a Phase 1 clinical trial for an entirely new type of drug called a Werner helicase inhibitor. Cindy’s tumor had a feature known as high microsatellite instability, so inhibiting Werner helicase, an enzyme that helps cancers repair DNA, would create a buildup of DNA damage, which would ultimately result in the death of cancer cells.

That was the theory, anyway. While the drug had shown promising results in preclinical models, Cindy was going to be the first ever human to take it. Side effects could be predicted based on laboratory models, but she was largely stepping into the unknown.

“I don’t remember being fearful or apprehensive about it,” she says. “But I remember when I came to Houston for the first treatment, the team was calling me ‘John Glenn Cindy’ for being the first patient on the trial. I not only felt confident it would work, but I was glad and felt fortunate to be part of something big,” she says.

One thing that helped them through the process is that Yap explained the science and the protocols behind the trial. Cindy said that was especially helpful for Dennis, a retired Unted States Navy officer whom she describes as “process focused.” He’s been keeping a careful journal of every encounter since Cindy’s diagnosis.