John Strickler headshot at a lab
John Strickler, MD

Cracking the Code: Charlotte Patient Benefits from DCI Precision Cancer Medicine Research


graphic of a target on a tumor with a red background

Charlotte-area resident Vickie Johnson, 72, was diagnosed with colon cancer in 2018 after seeking care twice for abdominal pain. First, she was diagnosed with appendicitis and had her appendix out. Then, when her pain persisted beyond the recovery period, she received a new diagnosis. A scan at the ER showed a possible tumor. She went back to her appendix surgeon, had the mass in her colon removed, and was referred to a hospital oncologist. He referred her to a second surgeon who performed an even more aggressive surgery to remove all the remaining cancer in her colon and got her started on chemotherapy.

Unfortunately, after each chemotherapy infusion she experienced severe chest pain. As she described it, “terrible spasms like I was having a heart attack.” Her oncologist didn’t have a plan b. “Finally, he said ‘I'm sorry, there's nothing I can do. We'll just test your blood every so often and get a scan every six months,’” Johnson shared. She wasn’t ready to give up, and as it turned out she didn’t need to.

Johnson’s next area oncologist — Justin Favaro, MD, PhD — who'd done his medical training at Duke, brought a cardio-oncologist onboard the care team. The two providers tweaked the chemotherapy regimen she’d been on with the first oncologist; adjusting the dosage so her heart would be able to tolerate it. That worked, but successive treatments didn’t make any headway against her cancer.

Johnson had begun 2019 in treatment for newly diagnosed colon cancer and ended that year with the death of her husband and progression of her cancer. During 2020, she’d endured another chemotherapy regimen but with no success. Cancer metastases remained in her liver and her lungs.

Patients with metastatic colorectal cancer who have progressed on standard chemotherapy receive limited benefit from the available standard of care options. Johnson had genomic testing done and it turned out her cancer was hardwired with a KRAS G12C mutation, an alteration found in 3 to 4% of all metastatic colorectal cancer cases. Favaro said there was one more option.

In the summer of 2021, he referred Johnson for enrollment in CodeBreaK 101, an early-stage  clinical trial (phase 1b/2) at Duke Cancer Institute testing a new approach to treating KRAS G12C-mutated solid tumor cancers — a new KRAS G12C inhibitor drug (sotorasib) in combination with other anti-cancer therapies of choice, including FDA-approved antibodies, immunotherapy, and chemotherapy drugs. DCI was one of the first institutions worldwide to open this trial, which had launched in December 2019.

Duke Cancer Institute GI medical oncologist and Associate Professor of Medicine John Strickler, MD, was Duke site principal investigator. Strickler is a colon cancer specialist who co-leads the DCI Precision Cancer Medicine and Investigational Therapeutics Research Program and the Molecular Tumor Board.

Johnson said she had “no hesitation” about her decision and was grateful when she qualified for recruitment to the study under the care of Strickler.

“This was the option. Nothing else was working,” Johnson recalled.

Treatment Evolution

The CodeBreaK 101 study had followed a global phase 1/2 clinical trial (CodeBreaK 100), for which Strickler was also Duke site PI, evaluating the safety and efficacy of sotorasib as a monotherapy in patients with KRAS G12C mutated locally advanced or metastatic solid tumor cancers who’d received at least one prior systemic therapy. Both CodeBreaK 101 and CodeBreaK 100 included non-small cell lung (NSCLC), pancreatic, colorectal, and other cancer cohorts.

After demonstrating an objective response rate of 36% in the CodeBreaK 100 phase 2 trial, sotorasib had received accelerated approval from the FDA as a monotherapy in NSCLC, making it the first KRAS G12C inhibitor to gain regulatory approval in the U.S.

While KRAS G12C inhibitors like sotorasib had shown significant activity against lung cancer, the responses in patients with colon cancer were short-lived. Results from the colorectal cancer cohort of CodeBreaK 100, published in the January 2022 issue of The Lancet (with Strickler as a co-author) would reflect only a 9.7% overall response rate. Investigators stated that sotorasib stood a better chance in colorectal cancer if it was paired with other drugs “to increase potential activity and overcome potential resistance mechanisms.”

Other studies had found that a tumor protein called EGFR (epidermal growth factor receptor) “rescued” KRAS G12C mutated colon cancer from sotorasib. Specifically, when patients with KRAS G12C mutated colon cancer received sotorasib, EGFR activated signaling of non-mutated KRAS proteins, thereby maintaining tumor growth signals.

Pairing with sotorasib an EGFR antibody called panitumumab (PMAb) to combat EGFR — one of many regimens tested in CodeBreaK 101 — was ‘just what the doctor ordered’ for *KRAS G12C mutated colorectal cancer. The new data, published in Nature Medicine (January 4, 2024) by Strickler and colleagues, revealed a much better overall response rate of 30%. 

“For years KRAS was thought to be an ‘undruggable target.’ The CodeBreaK 101 trial demonstrated for the first time that the combination of a KRAS inhibitor (sotorasib) together with an EGFR antibody (panitumumab) can control KRAS G12C mutated metastatic colon cancer with a chemotherapy free regimen,” said Strickler. “Patients experienced significant benefit. This represents a significant advance for patients with metastatic colon cancer and led to a large, randomized phase 3 trial (CodeBreaK 300 — evaluating sotorasib in combination with PMab) that confirmed this benefit.”

CodeBreaK 300 investigators announced at the European Society for Medical Oncology (ESMO) Congress in October 2023 and then reported in The New England Journal of Medicine that December that sotorasib at the standard dose of 960 mg/d plus PMab (in colorectal cancer) led to tumor shrinkage in 81% of patients and a 51% reduction in the risk of disease progression. Compared to current standard of care therapies this represents a significant advancement.

“These findings add to the precision cancer medicine revolution that has changed the way we treat metastatic cancers,” said Strickler, who with former DCI fellow Bennett Caughey, MD (now with Massachusetts General Hospital Cancer Center), published a review (January 2024) in the journal Drugs on “Targeting KRAS-Mutated Gastrointestinal Malignancies with Small-Molecule Inhibitors: A New Generation of Breakthrough Therapies.”

headshot of Kathy McCurdy in a blue Duke sweatshirt
“I get a lot of support from the people I meet with every other week like Dr. Strickler and Evan (Dropkin) and Kathy (McCurdy) and all the nurses who I come into contact with,” says colon cancer patient Vickie Johnson, 72.

A New Normal

Two-and-a-half-years since she enrolled, Johnson’s still on the CodeBreaK 101 study. The colon cancer metastases in her lungs and liver have diminished with the trial medication and supplemental radiation treatments.

“You know, even from the beginning of this whole journey … I don't wake up thinking ‘I have cancer,’” shared Johnson, who’s entering her sixth year of living with the disease and who’ll turn 73 in June.

Johnson takes eight pills a day of the sotorasib. She receives a monthly PMab infusion, and every-other-week monitoring at Duke Cancer Center — just a couple hours up the road from Charlotte. Other than dry eyes and a skin reaction akin to a chemical peel — which required a dose adjustment and continuing management — she’s been largely free of side-effects from this treatment. She still has some lingering neuropathy from her previous chemo treatments, but this too is manageable.

Johnson has the support of her sister, daughter, and teenage granddaughter who live close by. She continues to enjoy attending her granddaughter’s local dance competitions, calls and visits with her son in Oklahoma, connecting with friends in Charlotte and in Houston where she’s from, and filling in once or twice a month at her old job. Johnson’s mother, who’s in assisted living, relies on her and Johnson’s sister for daily care and companionship so keeping well for family is particularly important.

Strickler called the sotorasib/PMab drug combination, which is now under FDA review for emergency use authorization, “an emerging standard of care in patients with KRAS G12C mutated metastatic colorectal cancer that has progressed on standard chemotherapy.”

If and when this drug combination gets approved by the FDA, Johnson can opt to get her sotorasib pills, PMab infusions, and monitoring through her Charlotte oncologist and insurance will cover that cost. She can also opt stay with her team at Duke with whom, she confessed, she’s “gotten pretty attached.”

“We work very closely with home medical oncologists to ensure that we are coordinating care effectively. When and if Mrs. Johnson decides to get treatment closer to home, we will ensure that her care handoff is seamless,” said Strickler.

*NOTE: The sotorasib/PMab regimen is only recommended for colorectal cancer patients whose cancer is “hardwired” with a KRAS G12C mutation, not in colorectal cancer cases where a KRAS G12C mutation has been acquired to drive resistance to first-or-second line treatment with PMab.

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