MUC16-Targeted Bispecific T-Cell Engager Cleared for Trial in Ovarian Cancer, Other Tumors

The FDA has approved the investigational new drug (IND) application for Nanjing Lead Biolabs’ LBL-033, an anti-mucin16 (MUC16)/CD3 bispecific antibody T-cell engager (BiTE), for the treatment of ovarian cancer and other malignant tumors.

"I am pleased to see that the FDA has quickly approved the clinical trial application of LBL-033 in the United States, and I am grateful for the good suggestions given by the FDA during the IND review process. These have laid a good foundation for the rapid, high-quality and effective development of this new targeted immunotherapy," Charles Cai, MD, PhD, chief medical officer, Leads Biolabs, said in a statement. "LBL-033 adopts a unique BiTE molecule design to allow better drug aggregation in MUC16-overexpressing tumor cells and to reduce the non-specific activation of CD3, which may help improve efficacy and reduce side effects such as cytokine release syndrome. We look forward to the clinical evaluation of the safety and efficacy of this innovative drug in order to bring it to the general population of cancer patients as soon as possible."

The phase 1/2 trial that will soon initiate will be a multicenter, dose-escalation and expansion study that will primarily evaluate the safety, tolerability and pharmacokinetics of LBL-033, as well as determine the recommended phase 2 dose in the phase 1 portion. The phase 2 portion will primarily evaluate efficacy of LBL-033.

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LBL-033 is designed to specifically target and kill MUC16-positive cancer cells by promoting immune cytokine secretion and modifying the tumor microenvironment to be favorable to tumor immunity and promote tumor cell death. The MUC16 marker is expressed in epithelial cells and very highly expressed in malignant tumors including ovarian epithelial cancer, fallopian tube cancer, primary peritoneal cancer, endometrial cancer, pancreatic cancer, non-small cell lung cancer, and gastric cancer. MUC16 is also involved in regulating immune escape, tumor cell proliferation, and metastasis.

LBL-033 was granted clinical trial approval by the National Medical Products Administration in China in February 2023 and the first participant was dosed in the trial at Sun Yat-sen University Cancer Center in April 2023. The BiTE is the first targeting MUC16 to be approved for trials in China. Internationally, there are no MUC16-targeted BiTE products approved for marketing.

REFERENCE
The U.S. FDA approved the phase i/ii clinical trial application to evaluate LBL-033, an anti-MUC16/CD3 bispecific antibody developed by Leads Biolabs, in advanced solid tumors including ovarian cancer. News release. Nanjing Leads Biolabs. June 16, 2023. https://prnmedia.prnewswire.com/news-releases/the-us-fda-approved-the-phase-iii-clinical-trial-application-to-evaluate-lbl-033-an-anti-muc16cd3-bispecific-antibody-developed-by-leads-biolabs-in-advanced-solid-tumors-including-ovarian-cancer-301853126.html