Some rectal cancer patients can now skip surgery, chemo and radiation after FDA approves Jemperli
In a 154-patient trial, 71% of patients were treated with the immunotherapy alone and needed nothing else by the data cutoff. The approval covers only tumors with a specific DNA repair defect, about 3% of locally advanced rectal cancers.
The Food and Drug Administration granted accelerated approval on Oct 19 to Jemperli (dostarlimab-gxly) for some adults with locally advanced rectal cancer. Patients take it alone, as their first treatment. FDA says it may let some of them avoid the chemotherapy, radiation and surgery that are the usual path today.
Those treatments can affect bowel, urinary and sexual function and fertility, FDA says. Surgery can also bring serious complications, and some patients end up with a permanent colostomy.
Who qualifies
The label is narrow. It covers adults with previously untreated stage II or stage III rectal cancer, meaning the cancer has grown into nearby tissue or lymph nodes but has not spread to distant organs. The tumor must be mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), as shown by an FDA-authorized test.
Both terms describe tumors that can’t fix copying errors in their DNA. The errors pile up and make proteins the immune system can spot, which is why these tumors respond to immunotherapy. Jemperli blocks PD-1, a protein on immune cells that cancer uses to hide.
FDA cites published estimates that about 3% of locally advanced rectal cancers are dMMR or MSI-H. GSK’s release gives a wider figure, 5% to 10% of rectal cancers overall.
What the trials found
FDA based the approval on interim results from AZUR-1, a single-arm phase 2 trial in 154 patients. There was no comparison group. Patients got a 500 mg infusion every three weeks for nine doses, about six months.
At the data cutoff, 110 patients (71%) had been treated with Jemperli alone, received no other treatment, and had no disease progression. Another 26 (17%) had surgery, 13 (8%) got added drug therapy or radiation, and 1 had progressive disease. Median follow-up was 26.3 months.
The trial’s main measure was a clinical complete response that held for 12 months, judged by independent reviewers. That rate was 47% of 116 patients who could be evaluated. FDA notes 38 more patients had a complete response but less than 12 months of follow-up at the cutoff. Judged by the trial’s own investigators, the rate was 68% of 144 patients. None of the patients with a complete or near-complete response had their disease progress during follow-up.
FDA also reviewed an earlier Memorial Sloan Kettering study of 50 patients. All 50 responded, and 93% had a complete response that held for 12 months. None had chemoradiation or rectal surgery. Of the 27 patients followed for at least three years, one had the cancer come back in the same area.
Skipping surgery means close monitoring
Patients in AZUR-1 who had a complete response skipped surgery and moved to close monitoring instead. That meant endoscopy, rectal MRI and CT scans every four months for the first two years and every six months after that, according to FDA’s trial summary.
Because this is an accelerated approval based on interim results, GSK must keep following patients to show the responses last. The indication text in GSK’s release says the long-term risk of relapse is unknown.
Safety
Jemperli can cause the immune system to attack healthy organs, and those reactions can be severe or fatal. In rectal cancer patients, the most common side effects were fatigue (32%), rash (22%), diarrhea (18%) and itching (17%), per GSK. Serious adverse reactions occurred in 20% of patients, and 3% stopped the drug because of side effects.
FDA approved the application about four months ahead of its goal date under its National Priority Voucher pilot, the 11th approval under that program. Neither FDA’s nor GSK’s announcement includes a price.
Why it matters
Whether a patient gets this option depends on one tumor test at diagnosis, and choosing it swaps surgery for a scan and scope schedule every four months for two years.
