Objective:

The article examines the objective, findings, and clinical context described in FDA approves dostarlimab for advanced rectal cancer.

Approach:

• Approval: The FDA granted accelerated approval on October 19 for dostarlimab-gxly (Jemperli), for tumors identified as MSI-H or dMMR by an FDA-authorized test.
• AZUR-1: The primary supporting study was a multicenter, single-arm, open-label phase 2 trial of 154 patients. Participants received 500 mg intravenously every 3 weeks for 9 cycles; response was assessed by endoscopy, rectal MRI, and CT.
• Response management: Patients with a clinical complete response (cCR) entered nonoperative surveillance. Patients without cCR, or with recurrent or progressive disease, were evaluated for standard treatment.

Key Findings:

• In AZUR-1, 47% of 116 evaluable patients had a sustained cCR for at least 12 months; another 33% had cCR with less than 12 months of follow-up at data cutoff.
• The objective response rate in AZUR-1 was 79%; 38% of patients achieved a near-complete response.
• At median follow-up of 26.3 months, no progression was observed among patients classified as having sustained cCR, cCR, or near-complete response.
• Among all 154 treated patients, 110 (71%) received no additional cancer treatment and had no disease progression; 26 (17%) underwent surgery and 13 (8%) received additional systemic therapy or radiation.
• An investigator-led, single-arm trial of 50 patients reported a sustained cCR rate of 93% and an objective response rate of 100%; no patients received chemoradiation or rectal cancer surgery.

Interpretation:

The FDA’s accelerated approval was primarily supported by AZUR-1. The prescribing information warns of potentially severe or fatal immune-mediated adverse reactions, infusion-related reactions, complications after allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. Monitoring of liver enzymes, creatinine, and thyroid function is advised in the prescribing information.

Limitations:

• Both supporting studies were single-arm and lacked randomized comparators.
• Longer follow-up is needed to establish response durability.

Conclusion:

Dostarlimab-gxly is administered at 500 mg intravenously every 3 weeks for up to 9 cycles, until disease progression or unacceptable toxicity. Under the AZUR-1 protocol, patients achieving cCR undergo surveillance every 4 months for 2 years and every 6 months thereafter.

Sources:

• FDA
• DailyMed