JMT103, a novel therapeutic agent, has demonstrated promising efficacy and a manageable safety profile in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). The multicenter, single-arm, open-label, phase Ib/II study conducted across 24 centers in China, evaluated the efficacy and safety of JMT103 in 125 patients. The study, which ran from May 2020 to June 2023, provides evidence supporting JMT103 as a potential treatment option for GCTB.
Study Design and Patient Population
The study enrolled patients aged 18 years or older with pathologically confirmed unresectable or surgically-challenging GCTB. Unresectable GCTB was defined as tumors that could not be entirely removed surgically due to their size, location, or invasion of critical structures. Surgically-challenging GCTB included tumors where complete resection could lead to serious dysfunction or complications. Patients received JMT103 subcutaneously at a dose of 2 mg/kg every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR), assessed by histopathological or radiological evaluation based on predefined criteria.
Efficacy Results
The primary endpoint was histopathological or radiological OTR based on best response evaluated using the following response criteria: (1) elimination of at least 90% of giant cells relative to baseline; (2) radiologic complete or partial response of the target lesion within 12 weeks, as per mICDS or mEORTC criteria. Secondary endpoints included ORR and DCR throughout the study, TTP, changes in BPI-SF score, uNTx/Cr, and sCTx concentrations, safety, and immunogenicity.
Safety Profile
Treatment-emergent adverse events (TEAEs) were recorded throughout the study, with specific attention to adverse events of special interest (AESIs) such as hypocalcemia, hypophosphatemia, injection site reactions, hypercalcemia after end of treatment (EOT), osteonecrosis of the jaw (ONJ), and hypersensitivity. Safety was assessed based on the intensity and frequency of TEAEs, SAEs, AESIs, and anti-drug antibodies (ADA).
Impact on Pain and Functionality
Patient-reported pain and its interference with daily functioning were assessed using the Brief Pain Inventory-Short Form (BPI-SF). A minimal 2-point change from baseline BPI-SF score was considered a clinically meaningful reduction. The study demonstrated that JMT103 treatment led to clinically meaningful reductions in pain and improvements in daily functioning, offering a significant benefit to patients suffering from GCTB-related pain.
Conclusion
The results of this Phase Ib/II study suggest that JMT103 is an effective and reasonably safe treatment option for patients with unresectable or surgically-challenging GCTB. The observed tumor response, coupled with improvements in pain and functionality, highlights the potential of JMT103 to address the unmet medical needs in this patient population.
