The FDA has granted accelerated approval to dostarlimab (Jemperli, GSK) for rectal cancer indications.
The drug is now approved for adults with stage II/III locally advanced rectal cancer (LARC) that is microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR).
The PD-1 inhibitor is the first immunotherapy to be approved specifically for MSI-H or dMMR rectal cancer, which accounts for 5%-10% of tumors. Based on the results of the approval study, AZUR-1, GSK said dostarlimab could help eligible patients avoid chemotherapy, radiation, and surgery.
Dostarlimab carries previous approvals for endometrial cancer and dMMR recurrent or advanced solid tumors. A patient’s eligibility for the drug’s new rectal cancer indications needs to be determined by an FDA-authorized test.
AZUR-1 was a single-arm study of 154 previously untreated MSI-H or dMMR LARC patients treated with 500 mg dostarlimab intravenously every 3 weeks for up to nine cycles.
Clinical complete response at 12 months (cCR12) by independent central review, the primary outcome, was 47% (54/116 evaluable patients). In addition, 38 patients (33%) who had been followed less than 12 months at data cutoff had a cCR. The objective response rate (ORR) was 79%. Sixty-eight percent of evaluable patients (98/144) achieved a cCR12 by investigator analysis, with an ORR of 82%. No disease recurrences have been reported among responders after a median follow-up of more than 2 years. Of 15 patients who underwent surgery after dostarlimab monotherapy, 12 were found to have had a pathologic complete response.
The FDA also reviewed a single-arm, open-label trial in 50 patients with previously untreated disease. The cCR12 rate was 93% and ORR was 100%; none of the patients received chemoradiation and/or surgery as part of treatment. Of the 27 patients followed at least 3 years, only one had a local recurrence, which was treated with lymphadenectomy.
The most common adverse reactions in AZUR-1 were fatigue (32%), rash (22%), diarrhea (18%), and pruritus (17%), with 3% of patients discontinuing due to adverse events. Twenty percent of patients had serious adverse reactions.
Labeling contains warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
The recommended dostarlimab dose is the same as in the studies, 500 mg every 3 weeks for up to nine cycles.
The approval was made under the FDA’s National Priority Review Voucher pilot program. Continued approval for the indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s), GSK noted.
M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net
