Building on the buzz around a celebrated early trial readout, GSK’s Jemperli has earned a first-in-class FDA approval in a specific type of rectal cancer.
Monday's accelerated approval makes Jemperli the first immunotherapy for patients with stage 2 and 3 locally advanced rectal cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), a type of genomic abnormality.
Other PD-1 immune checkpoint inhibitors such as Merck & Co.’s Keytruda boast broad MSI-H/dMMR labels, including in colorectal cancer, but only for unresectable or metastatic tumors—until recently. Jemperli’s rectal cancer nod comes a few days after the FDA cleared Roche’s Tecentriq, used alongside chemo, as a post-surgical treatment for patients with stage 3 dMMR colon cancer.
Jemperli’s green light offers eligible rectal cancer patients an option that could help them avoid traditional interventions like chemotherapy, radiation and life-altering surgery.
Infertility is a growing problem with traditional standard of care in rectal cancer as younger patients get diagnosed, Andrea Cercek, M.D., from Memorial Sloan Kettering Cancer Center, who led the clinical study that earned Jemperli’s approval, pointed out during a press briefing ahead of the approval. About 30% of patients need a permanent colostomy, which involves removing a section of the colon or rectum, she noted.
“With just Jemperli alone, we were able to offer the majority of patients complete normal organ preservation, normal pelvic function, which was really unheard of in standard of care in rectal cancer,” she said.
So far, five babies have been born to patients from an initial academic study led by Cercek, including four to two women who “100% would not have been able to have children due to the location of their tumor” and the fact that pelvic radiation therapy can induce menopause, she said.
Jemperli’s potential in MSI-H/dMMR rectal cancer caught public attention in 2022 when initial results from a small study conducted by Cercek at Sloan Kettering showed every patient experienced a complete response. The strong efficacy signal was not a complete surprise given that MSI-H/dMMR tumors are known to be “hot” tumors that are more visible to the immune system and are therefore more amenable to immunotherapies like Jemperli.
Following the media publicity and a vote of support from an advisory committee, the FDA apparently signed off on GSK’s plan of using complete response data from more patients in a larger single-arm trial—versus a randomized study—to support an accelerated approval in this rare cancer type. MSI-H/dMMR tumors only constitute 5% to 10% of all rectal cancers, of which there have been an estimated 50,000 new cases across all stages in the U.S. in 2026.
Then this July, GSK announced that the global phase 2 Azur-1 trial met its primary endpoint at an interim analysis, showing a “meaningful and sustained” clinical complete response rate for Jemperli at 12 months, or cCR12, which is measured by tumor imaging.
While detailed data are slated for presentation at the European Society for Medical Oncology annual meeting, the FDA’s approval now reveals that 47% of 116 evaluable patients achieved cCR12. That data point is still maturing as more patients continue to reach the 12-month landmark, GSK’s global head of oncology R&D, Hesham Abdullah, M.D., said during the press briefing.
That analysis of the trial’s primary endpoint was based on independent central review. Per investigator analysis, a key secondary endpoint, 68% of 144 evaluable patients achieved cCR12. In an exploratory analysis, an additional 12 patients (8%) were found to have pathological complete response, as their surgically resected tissue had no sign of cancer.
To date, none of the responders have seen their disease return after a median follow-up of more than two years, according to Cercek and GSK.
“One of the things that we have observed in the data is that the investigator-assessed clinical complete responses tend to occur earlier and also have the most follow-up,” Abdullah said.
Because the trial was conducted in different parts of the world, Abdullah argued that clinical complete responses by investigator assessment are “probably the most relevant” in practice.
As the go-ahead was granted under the FDA’s accelerated approval pathway, GSK is required to confirm Jemperli’s benefit. The company’s phase 3 Azur-2 trial could serve that purpose. The ongoing study is evaluating Jemperli, used both before and after surgery, against post-surgical chemo or observation in stage 3, MSI-H/dMMR resectable colon cancer. It is expected to read out in 2028, Abdullah said.
Roche’s PD-L1 inhibitor Tecentriq was recently approved in this tumor type alongside chemo as a post-surgical treatment after showing the regimen improved disease-free survival by 50% compared with chemo alone.
GSK is investing in other assets with potential in colorectal cancer. The British pharma recently paid Hutchmed $110 million upfront to license a near-clinical candidate that pairs an EGFR antibody with a KRAS inhibitor payload. Colorectal cancer is one of its initial target indications.