FDA Grants Fast Track Designation to AMB-05X in Tenosynovial Giant Cell Tumors

The FDA has granted fast track designation to AMB-05X for the treatment of patients with tenosynovial giant cell tumor (TCGT), according to an announcement by AmMax Bio.¹

AMB-05X is a potent monoclonal antibody targeting CSF1R. Through its binding to the regulatory cytokines CSF1 and IL-34, CSF1R is involved in the regulation of macrophages and related cells in multiple biological processes against multiple organ systems.

“We are very pleased to receive fast track designation for AMB-05X from the FDA, which clearly reflects the significant unmet need facing thousands of patients suffering from TCGT and its numerous associated co-morbidities,” Larry Hsu, PhD, chief executive officer of AmMax Bio, stated in a press release.

“Physicians have shown tremendous enthusiasm for a locally injectable form of CSF1R inhibitor to address this localized disease in the joint,” he added. “AMB-05X is designed to be administered via an intra-articular injection at the site of the tumor to minimize the systemic exposure and the associated serious safety concerns.”

Though surgical resection is the standard of care for patients with TGCT, the risk of infections, prolonged post-operative care, and frequent relapse has created a need for a medical therapy to use alongside surgery.

AMB-05X is currently under investigation in multiple phase 2 trials for patients with TGCT. Previously reported interim data from a phase 2 trial (NCT04731675) of 5 patients showed that AMB-05X demonstrated clinical benefit, including tumor reduction per RECIST v1.1 criteria and improvements in patient-reported functional outcomes, in patients with TGCT of the knee.² Findings also showed AMB-05X was well tolerated with no serious adverse effects (AEs) and limited non-serious grade 1/2 AEs.

The multicenter, phase 2 trial aimed to enroll approximately 12 patients with TGCT of the knee to receive 6 doses of AMB-05X over 12 weeks. Patients were required to be at least 18 years old with a confirmed diagnosis of TGCT of the knee joint and measurable disease per RECIST v1.1.³ Adequate hematologic, hepatic, and renal function was also necessary.

Patients were excluded from the trial if they received treatment with another investigational drug within 4 weeks or 5 half-lives of baseline; received prior CSF1, CSF1R, or oral TKIs; had a history of extensive knee surgery; or had metastatic TGCT.

Enrolled patients received an injection of AMB-05X once every 2 weeks for 12 weeks. The co-primary end points of the trial were treatment-emergent AEs and tumor response per RECIST v1.1. Secondary end points included tumor volume reduction, plus mean change in range of motion of the knee, patient-reported outcomes, stiffness, and pain.

Another ongoing phase 2 trial (NCT04938180) is investigating intravenous AMB-05X in patients with TGCT.⁴ Injections of the agent will also be evaluated in patients with TCGT in the phase 2 AMB-051-07 trial (NCT05349643) that features a long-term extension as a part of the protocol.⁵

References

1. AmMax Bio announces AMB-05X granted FDA fast track designation for the treatment of tenosynovial giant cell tumor (TGCT). News release. AmMax Bio. September 7, 2022. Accessed September 7, 2022. https://bit.ly/3QoWcW8
2. AmMax Bio announces positive interim phase 2 results of AMB-05X for the treatment of tenosynovial giant cell tumor (TGCT). News release. AmMax Bio. October 20, 2021. Accessed September 7, 2022. https://bit.ly/3Ql5Vgd
3. An open-label study of intra-articular AMB-05X injections in subjects with tenosynovial giant cell tumor of the knee. ClinicalTrials.gov. Updated July 29, 2022. Accessed September 7, 2022. https://clinicaltrials.gov/ct2/show/NCT04731675
4. A phase 2 study of intravenous AMB-05X in tenosynovial giant cell tumor patients. ClinicalTrials.gov. Updated July 29, 2022. Accessed September 7, 2022. https://clinicaltrials.gov/ct2/show/NCT04938180
5. A phase 2 study with LTE to evaluate safety and efficacy of AMB-05X injections in subjects with TGCT. ClinicalTrials.gov. Updated April 27, 2022. Accessed September 7, 2022. https://clinicaltrials.gov/ct2/show/NCT05349643