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FDA Approval: Dostarlimab (Jemperli) for Uterine Cancer
FDA approved Dostarlimab (Jemperli), an anti-PD-1 checkpoint inhibitor, for certain people with uterine cancer. What was approved, the evidence, and what it does and doesn't mean.
Original commentary from the Cancer Explained editorial team.
Please note: this page is educational only — it is not medical advice, and it does not speculate about anyone’s health beyond reliable public reporting. For questions about your own health, talk with your healthcare team.
The proofreader that stopped working
Every time a cell copies its DNA it makes mistakes. A set of proteins called the mismatch repair system finds and fixes them. It is the spellchecker of the genome.
In some tumors that system is broken. The shorthand is dMMR, for mismatch repair deficient. Errors pile up unchecked, especially in short repeating stretches of DNA called microsatellites. That instability is the other name for the same problem: MSI-high.
Endometrial cancer starts in the lining of the uterus, and it is one of the cancers where dMMR shows up often.
Why a broken spellchecker helps the immune system
A tumor stuffed with mutations makes many abnormal proteins. Abnormal proteins look foreign, and foreign is what the immune system attacks.
So dMMR tumors should be highly visible. The problem is that they also learn to switch the immune system off.
The switch is PD-1, a receptor on T cells. When PD-1 binds its partners PD-L1 or PD-L2, the T cell stops multiplying and stops making the signals that drive an attack. Tumors turn up production of those partners and use the brake against the body.
Dostarlimab, sold as Jemperli, is a humanized monoclonal antibody that binds PD-1 and blocks it from meeting PD-L1 and PD-L2. Releasing the brake lets the anti-tumor response resume.
Two approvals, four years apart
In April 2021 the FDA gave dostarlimab accelerated approval. It covered adults with dMMR recurrent or advanced endometrial cancer that had progressed on or after platinum chemotherapy.
Accelerated approval is provisional. A drug reaches patients on an early measure such as tumor response, on condition that the benefit is confirmed later.
On February 9, 2023 the FDA made that a regular approval. The wording tightened. The tumor must be dMMR on an FDA-approved test. The cancer must have progressed on or after a prior platinum regimen in any setting. And the person must not be a candidate for curative surgery or radiation.
The label has grown since. Dostarlimab is now also indicated with carboplatin and paclitaxel, then alone, for primary advanced or recurrent endometrial cancer.
What GARNET showed
The evidence for the regular approval came from GARNET, a multicenter, multicohort, open-label trial in advanced solid tumors.
The relevant group was 141 patients with dMMR recurrent or advanced endometrial cancer that had progressed after platinum chemotherapy.
The main measures were overall response rate and how long responses lasted, judged by blinded independent reviewers.
Confirmed overall response rate was 45.4 percent. That split into a 15.6 percent complete response rate, meaning no detectable tumor, and 29.8 percent partial response.
Median duration of response was not reached, which means more than half of responders were still responding when the data were analyzed. Of those who responded, 85.9 percent had responses lasting more than 12 months and 54.7 percent more than 24 months.
Durability is the point of that last sentence. Chemotherapy responses in this setting are usually measured in months.
The side effects of taking a brake off
More than 20 percent of patients had fatigue or weakness, anemia, rash, nausea, diarrhea, constipation or vomiting.
The distinctive risks are immune-mediated. Releasing the brake anywhere releases it everywhere, and the immune system can turn on healthy organs. The FDA names six patterns. Pneumonitis is inflammation of lung tissue. Colitis is inflammation of the colon. Hepatitis is inflammation of the liver. Endocrinopathies means damage to hormone glands such as the thyroid. Nephritis comes with reduced kidney function. Skin reactions round out the list.
These can appear weeks or months after a dose. That is why a new cough, lasting diarrhea, or sudden exhaustion gets reported rather than waited out. Our page on immunotherapy sets out what that monitoring looks like.
When to get checked
Endometrial cancer has an unusually clear warning sign, and it is the reason this cancer is often caught early.
NCI says to check with a doctor for:
- Vaginal bleeding or discharge unrelated to periods.
- Vaginal bleeding after menopause.
- Difficult or painful urination.
- Pain during sex.
- Pain in the pelvic area.
Any bleeding after menopause deserves an appointment. Not a wait-and-see, and not a next-annual-checkup. It is usually not cancer, and that is the whole reason it is worth checking.
A Pap test does not do this job. NCI is explicit that endometrial cancer begins inside the uterus and does not usually show up in Pap results. Diagnosis needs tissue: an endometrial biopsy, in which a thin flexible tube is passed through the cervix to scrape a small sample, or a dilatation and curettage. Our page on uterine cancer symptoms covers what happens after each result.
Where this sits in the wider picture
SEER carries an American Cancer Society projection of 68,270 new US uterine cancer cases and 14,450 deaths for 2026. Median age at diagnosis is 64.
Five-year relative survival for cases from 2016 to 2022 is 80.9 percent overall. By spread at diagnosis: 94.9 percent while confined to the uterus, 70.1 percent with regional lymph nodes involved, and 19.9 percent for distant disease. Sixty-seven percent are found while still localized, which is what postmenopausal bleeding buys.
Those averages cover every uterine cancer in the registry, including uterine sarcoma, which behaves differently. They describe a population, not a person. They say nothing about the advanced dMMR setting this drug treats.
What this approval cannot tell you
GARNET had no control group in this cohort. There is no head-to-head comparison and no survival difference to quote.
The measure was tumor shrinkage, not lifespan. Response rate and survival are related, but they are not the same thing.
It applies only to dMMR tumors, established by an approved test. Even so, roughly half the patients did not respond.
People needing immune suppression for autoimmune disease were excluded, as were people already given a PD-1 or PD-L1 blocker. The trial says nothing about either group.
And the label has changed twice since 2021. Which indication fits one person depends on mismatch repair status, what treatment came before, and whether surgery or radiation could still cure.
Sources
- FDA D.I.S.C.O. Burst Edition, FDA approval of Jemperli (dostarlimab-gxly) for dMMR endometrial cancer — https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-jemperli-dostarlimab-gxly-dmmr-endometrial-cancer
- FDA prescribing information for JEMPERLI, via the openFDA drug label API — https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22JEMPERLI%22&limit=1
- NCI PDQ, Endometrial Cancer Treatment (Patient Version) — https://www.cancer.gov/types/uterine/patient/endometrial-treatment-pdq
- SEER Cancer Stat Facts, Uterine Cancer — https://seer.cancer.gov/statfacts/html/corp.html
How this article was prepared
An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.
The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.
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Put the story in context
Prevention, possible warning signs, screening, and diagnosis
This story relates to Uterine cancer. The information below is general: it does not reveal anything else about a public person’s health, and not every point applies to every cancer. Personal advice depends on age, symptoms, family history, exposures, and medical history.
Prevention and risk reduction
Not every cancer can be prevented. Avoiding tobacco, protecting skin from ultraviolet radiation, limiting alcohol, staying active, and receiving recommended HPV or hepatitis B vaccination can lower the risk of certain cancers. A risk factor is not a prediction or a cause in one individual.
Symptoms and possible early signs
Possible signs vary and are often caused by conditions other than cancer. Changes worth discussing include a new lump, unexplained bleeding or weight loss, a persistent cough, lasting bowel or bladder changes, a changing skin spot, or symptoms that persist or worsen. Some early cancers cause no symptoms.
Screening and early detection
Screening looks for certain cancers before symptoms begin. Recommended tests exist only for some cancers and depend on age and risk. Screening can have benefits and harms; it is not the same as evaluating a new symptom, and there is no single routine scan or blood test that reliably screens for every cancer.
How cancer is diagnosed
Diagnosis may involve a history and exam, imaging, laboratory tests, and often a biopsy. Pathology can identify the cancer type and may test biomarkers that guide treatment. Symptoms, screening results, tumor markers, or online stories alone cannot confirm cancer.
Learn about this story’s cancer topic
A public story may encourage questions, but it should not be used to estimate your risk or choose testing. Contact a healthcare professional about a persistent or concerning change. Seek urgent care for severe or rapidly worsening symptoms.