RC-88 Advanced Drug Monograph

RC-88 (English: RC-88)

Generic Name: Misitatug Blivedotin Drug Type: Antibody-drug conjugate (ADC) Target: Mesothelin (MSLN) Payload: Monomethyl auristatin E (MMAE) Developer: RemeGen Biosciences (Shandong China) Manufacturer: Yantai Rongchang Biological Engineering (manufactured by MabPlex) Clinical Domain: Oncology Clinical Indication:

• Mesothelioma
• Bile Duct Carcinoma
• Pancreatic cancer
• Lung Adenocarcinoma
• Ovarian Cancer
• Other Solid Tumors Development Status: Phase 1 and Phase 2 (in China) Regulatory Decisions:
• January 2024: Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) for the treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.
• December 2023: Investigational new drug (IND) approval by the U.S. FDA for a Phase 2 clinical trial in gynecological tumors.
• March 2023: Approval by the CDE (China) for a Phase I/II clinical study in combination with Sintilimab for advanced malignant solid tumors. Clinical Trials:
• NCT06173037: RC88 in Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer (Phase 2, multi-country, open-label, randomized, dose-optimization).
• NCT06016062: A Study of RC148 As a Single Agent and Combination Therapy in Patients with Locally Advanced Unresectable or Metastatic Malignant Solid Tumors.
• NCT05804526: A Study of RC88 Combined With Sintilimab for Advanced Solid Tumours (Phase I/II, China).
• NCT05508334: A Study to Assess the Safety and Tolerability of RC88 for Patients With Advanced Solid Tumours (Phase 1).
• NCT04175847: A Phase I/IIa Study of RC88-ADC in Subjects With Advanced Malignant Solid Tumors. Mechanism of Action: RC88 is composed of a humanized anti-mesothelin antibody conjugated via a cleavable linker to MMAE, a microtubule-disrupting agent. It binds to mesothelin-expressing tumor cells, leading to internalization and release of MMAE, resulting in cell cycle arrest and apoptosis. Molecular Formula (Estimated): C6506H10042N1718O2026S50 Molecular Weight (Estimated): 146346.902 Da (average) Other Names/Synonyms: RC 88, RC88 UNII (FDA): NS5GTS5FLQ CAS Registry Number: 2767203-06-3 Origin Clone Species: Mus musculus (chimeric antibody) Expression System: CHO (Chinese Hamster Ovary) cells Linker: Cleavable, divalent linker Drug/Payload: Monomethyl auristatin E (MMAE) conjugated on an average of 4 cysteinyl residues.