A small but heralded clinical trial at Memorial Sloan Kettering Cancer Center (MSK) that saw rectal cancer disappear in 100% of people who took part has taken a step towards approval by the Food and Drug Administration (FDA).
The form of immunotherapy used in the trial, called Jemperli (dostarlimab) and produced by the drug company GSK, received the FDA’s “Breakthrough Therapy Designation” on December 16, 2024, for treating people with a particular type of rectal cancer. The FDA says this breakthrough designation aims to “expedite the development and review of drugs that are intended to treat a serious condition” where clinical data show “substantial improvement over available therapy.”
This trial’s new approach, which uses immunotherapy alone, benefits a subset of patients who have tumors with specific genetic characteristics known as mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI).
Using immunotherapy alone means that people are spared the standard treatment for rectal cancer, which includes surgery, radiation, and chemotherapy. These therapies, while generally effective, can have life-altering side effects, including infertility, incontinence, and more.
“Everyone on the clinical trial is doing great,” says MSK gastrointestinal oncologist Andrea Cercek, MD, who led the clinical trial with gastrointestinal oncologist Luis Diaz, MD.
They reported updated results in June 2024, more than doubling the number of patients who have been have been successfully treated. “So far, 42 people have completed treatment, and all of them have no evidence of disease. Side effects were quite mild and well tolerated.”
She adds: “This new treatment is also proving very durable. Most people on the trial have been free of cancer for at least a year, and the original participants have been healthy for up to four years and counting. The success rate remains 100%.”
Changing Practice Around the World
Dr. Cercek reported the updated results in June 2024 at ASCO, the country’s premier conference on cancer. When she announced the first set of results at the same conference in 2022, the news made headlines around the world and were simultaneously published in the New England Journal of Medicine.
Since then, Dr. Cercek reports that the approach pioneered at MSK “has been adopted by many doctors in the U.S. and around the world. I get letters thanking us from America, Australia, Ireland, and other countries, which is really gratifying.”
The National Comprehensive Cancer Network, the doctors’ group that sets guidelines for cancer treatments in the U.S., officially changed their directives for treating rectal cancer as a result of the clinical trial, which makes insurers more willing to cover the approach.
The trial has even sparked a small baby boom. “Three people who participated in the MSK trial have had healthy babies since finishing treatment,” says Dr. Cercek, who met one of these newborns days after her birth. “That would have been nearly impossible for women treated with the standard treatment of surgery, radiation, and chemotherapy — which can make both genders infertile.”
Clinical Trial Success with the First Patient
Sascha Roth, the first patient in the clinical trial, remembers getting a momentous phone call on a hectic Friday evening.
She was racing around her home in Washington, D.C., to pack for New York, where she had been scheduled to undergo weeks of radiation therapy for rectal cancer.
Sascha, then 38, had undergone six months of immunotherapy in the clinical trial. And Dr. Cercek had called to relay the happy news that her latest tests showed no evidence of cancer.
The call changed everything, Sascha says, and left her “stunned and ecstatic — I was so happy.”
Immunotherapy harnesses the body’s own immune system as an ally against cancer. The MSK clinical trial was investigating — for the first time ever — if immunotherapy alone could beat rectal cancer that had not spread to other tissues, in a subset of patients whose tumor contain a specific genetic mutation.
Remission of Rectal Cancer
These same remarkable results would be repeated for all 42 people — and counting — in the MSK clinical trial. In every case, the rectal cancer disappeared after immunotherapy — without the need for the standard treatments of radiation, surgery, or chemotherapy. And the cancer has not returned in any of the patients, who have been cancer-free for up to four years.
“It’s incredibly rewarding,” says Dr. Cercek, “to get these happy tears and happy emails from the patients in this study who finish treatment and realize, ‘Oh my God, I get to keep all my normal body functions that I feared I might lose to radiation or surgery.’
Using Immunotherapy Earlier To Target a Genetic Mutation
Drs. Cercek and Diaz explain that their team’s research was sparked by two key ideas.
The first premise, says Dr. Diaz, is to figure out precisely which patients benefit most from immunotherapy, so they can receive it right away. “Immunotherapy has proven successful in treating a subset of patients with colon and rectal cancer that has metastasized, meaning spread to other tissues.”
The patients in this subset, Dr. Diaz explains, have tumors with a specific genetic makeup known as mismatch repair-deficient (MMRd) or microsatellite instability (MSI).
Between 5% and 10% of all rectal cancer patients are thought to have MMRd tumors, including all the patients in the MSK clinical trial that Sascha participated in. There are 45,000 Americans diagnosed a year with rectal cancer.
“An MMRd tumor develops a defect in its ability to repair certain types of mutations that occur in cells. When those mutations accumulate in the tumor, they stimulate the immune system, which attacks the mutation-ridden cancer cells,” says Dr. Diaz, who heads the MSK division of Solid Tumor Oncology and holds the Grayer Family Chair.