The US Food and Drug Administration (FDA) has granted accelerated approval todostarlimab-gxly (Jemperli) for adults with previously untreated, stage II/III locally advanced rectal cancer that is microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR), as determined by an FDA-authorized testfor solid tumors, according to an agency press release.
The October 19 approval, granted 4 months ahead of the FDA's target date, introduces an immunotherapy treatment option for this population. In the supporting clinical trials, patients who achieved a clinical complete response (cCR) following treatment entered nonoperative management with close surveillance rather than proceeding directly to chemoradiation or surgery.
Approval was primarily supported by AZUR-1, a multicenter, single-arm, open-label phase 2 trial involving 154 patients with previously untreated MSI-H/dMMR stage II/III rectal cancer. Patients received dostarlimab-gxly 500 mg intravenously every 3 weeks for 9 cycles. Tumor response was assessed using endoscopy, rectal MRI, and CT imaging. Patients achieving cCR entered a nonoperative surveillance program, while those without cCR or with recurrent or progressive disease were evaluated for standard treatment.
The primary efficacy endpoint was sustained clinical complete response for 12 months, assessed by independent central review. Among 116 evaluable patients, the sustained cCR12 rate was 47%. An additional 38 patients (33%) achieved clinical complete response but had less than 12 months of follow-up at data cutoff, and 44 patients (38%) achieved a near-complete response.
The objective response rate was 79%. At a median follow-up of 26.3 months, no disease progression was observed among patients classified as having sustained cCR, cCR, or near-complete response.
Of the 154 treated patients, 110 (71%) received dostarlimab alone without additional cancer treatment or disease progression. Another 26 (17%) underwent surgery, and 13 (8%) received additional systemic therapy or radiation.
The FDA also reviewed an investigator-led, single-arm trial involving 50 patients. The sustained cCR rate was 93%, and the objective response rate was 100%. No patients received chemoradiation or rectal cancer surgery.
Both studies lacked randomized comparators, and longer follow-up is needed to establish durability of response.
The prescribing information warns of potentially severe or fatal immune-mediated adverse reactions, infusion-related reactions, complications following allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. Clinicians should monitor liver enzymes, creatinine, and thyroid function during treatment.
Dostarlimab-gxly is administered at 500 mg intravenously every 3 weeks for up to 9 cycles, until disease progression or unacceptable toxicity. Patients achieving cCR require surveillance every 4 months for the first 2 years and every 6 months thereafter, according to the AZUR-1 protocol.
