Drug intelligence / Profile preview

lutetium Lu 177 dotatate + pembrolizumab

Development stage
Phase 2
Lead developer
Novartis
Modality
Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics, Beta-minus Emitters → Radiopharmaceuticals, Gamma Emitters → Radiopharmaceuticals, Monoclonal Antibodies → Antibody-Based Therapeutics, Peptides
Administration
Intravenous
01

Overview

This combination therapy consists of the radiopharmaceutical lutetium Lu 177 dotatate (Lutathera) and the immune checkpoint inhibitor pembrolizumab (Keytruda). Lutetium Lu 177 dotatate is a peptide receptor radionuclide therapy (PRRT) that targets somatostatin receptors (SSTR), which are frequently expressed on the surface of neuroendocrine-derived tumor cells. Upon binding, the drug is internalized, delivering cytotoxic beta radiation (from the lutetium-177 isotope) directly to the tumor cells, causing DNA damage and cell death. Pembrolizumab is a humanized monoclonal antibody that targets the programmed cell death protein 1 (PD-1) receptor on T cells. By blocking the interaction between PD-1 and its ligands (PD-L1 and PD-L2), pembrolizumab prevents the inhibition of T-cell activity, thereby enhancing the immune system's ability to recognize and destroy cancer cells. This specific combination is being investigated by Weill Medical College of Cornell University in the Phase 2 iPRRT trial for patients with metastatic or unresectable Merkel cell carcinoma who have progressed on prior anti-PD-1/L1 immunotherapy.

Other names
177Lu-DOTATATE + pembrolizumabLutetium (177Lu) oxodotreotide + pembrolizumab
02

Targets

PDCD1 (Programmed cell death protein 1 receptor)SSTR1 (Somatostatin Receptor Type 1)SSTR2 (Somatostatin receptor type 2)SSTR3 (Somatostatin receptor 3)SSTR4 (Somatostatin receptor 4)SSTR5 (Somatostatin receptor 5)SSTR (Somatostatin receptors)

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