Dalotuzumab (MK-0646): A Comprehensive Review of its Development and Clinical Evaluation in Oncology

1. Executive Summary

Dalotuzumab, also known by its development code MK-0646, is an investigational, humanized IgG1 monoclonal antibody developed by Merck & Co., Inc., under license from Pierre Fabre SA.[1] Designed as a targeted therapy for various cancers, Dalotuzumab specifically binds to the Insulin-like Growth Factor 1 Receptor (IGF-1R), a key component of a signaling pathway implicated in cancer cell proliferation, survival, and resistance to therapy.[1] By inhibiting IGF-1R activation by its ligands (IGF-1 and IGF-2), Dalotuzumab aimed to block downstream signaling cascades, induce apoptosis, and potentially elicit antibody-dependent cellular cytotoxicity.[1]

The clinical development program for Dalotuzumab was extensive, encompassing numerous Phase I, II, and III trials across a spectrum of malignancies, including metastatic colorectal cancer (mCRC), non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer, small cell lung cancer (SCLC), and multiple myeloma.[1] It was evaluated both as a monotherapy and, more frequently, in combination with standard-of-care treatments such as chemotherapy (e.g., pemetrexed/cisplatin, irinotecan), EGFR inhibitors (e.g., cetuximab, erlotinib), and inhibitors of the PI3K/Akt/mTOR pathway (e.g., ridaforolimus).[5]