Dostarlimab — Drug Monograph

Brand names: Jemperli

Drug class: Checkpoint Inhibitor

Mechanism of Action

Humanized IgG4 monoclonal antibody targeting PD-1. Blocks PD-1/PD-L1 and PD-1/PD-L2 interactions, restoring effector T cell function in the tumor microenvironment. Particularly active in tumors with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), where a high mutational burden generates abundant neoantigens that prime T cell responses.

FDA Indications

• Endometrial cancer — primary advanced or recurrent dMMR (mismatch repair-deficient) endometrial cancer (with carboplatin + paclitaxel, then dostarlimab maintenance — RUBY trial)
• dMMR/MSI-H solid tumors — recurrent or advanced, after prior platinum-containing therapy (tumor-agnostic approval)

Common Side Effects

• Fatigue
• Nausea
• Diarrhea
• Constipation
• Anemia
• Rash
• Hypothyroidism
• Alopecia (when combined with chemotherapy)

Clinical Pearl

The RUBY trial is landmark: dostarlimab + carboplatin/paclitaxel followed by dostarlimab maintenance showed dramatic improvement in PFS for dMMR advanced endometrial cancer (HR 0.28 for dMMR subgroup) — essentially redefining first-line treatment for this molecular subgroup. A separate exploratory report of dostarlimab in locally advanced dMMR rectal cancer showed complete clinical response in 100% of the first 12 evaluable patients, with all avoiding surgery — a practice-changing result now…

Related Therapies & Mechanisms

• Pembrolizumab (Keytruda) — Checkpoint Inhibitor · CRC
• Nivolumab (Opdivo) — Checkpoint Inhibitor · CRC
• Atezolizumab (Tecentriq) — Checkpoint Inhibitor
• Avelumab (Bavencio) — Checkpoint Inhibitor