FDA Clears IND for OriCAR-017 in Relapsed/Refractory Multiple Myeloma

• The clearance of the investigational new drug (IND) application for OriCAR-017 is supported by findings from the POLARIS study (NCT05016778).

• OriCAR-017 is a chimeric antigen receptor (CAR) T-cell therapy designed to target GPRC5D.

• With the IND application clearance, Oricell Therapeutics may now start the clinical development for OriCAR-017 in the United States without delay.

The FDA has cleared the IND application for OriCAR-017 for the treatment of patients with relapsed/refractory multiple myeloma (RRMM).¹

This IND approval for OriCAR-017 follows its IND approval from the National Medical Products Administration in 2023, which were based on findings from the POLARIS study. All 10 patients in the trial with RRMM responded to the therapy per International Myeloma Working Group (IMWG) criteria, and the overall response rate (ORR) was 100%. The stringent complete response rate was 80%, and a 100% minimal residual disease-negative rate was detected at day 28. This result was further confirmed at month 3.

Forty percent of patients had extramedullary disease, 50% of patients had received prior BCMA CAR T-cell therapies, 70% had high-risk cytogenetics, 70% had an ECOG performance status of 2, and 80% had international staging system stage II and III disease. For safety, OriCAR-017 was well-tolerated. No Immune effector cell-associated neurotoxicity syndrome, cerebellar disorder, or delayed infections were reported.

"The evidenced superior safety, efficacy and durability profile of OriCAR-017 is truly exciting and will significantly benefit multiple myeloma patients on a global scale. Ten years' R&D cumulates not only OriCAR-017 but also the robust and integrated technology platforms that generate one-of-its-kind CAR-T products for liquid and solid tumors," said Peter He, co-founder and chief scientific officer of Oricell, in a press release.

OriCAR-017 is a CAR T-cell therapy designed to specifically target GPRC5D. Utilizing Oricell's exclusive platforms and specialized CMC expertise, this therapy is engineered to achieve optimal binding, enhanced persistence, and superior antitumor efficacy through rejuvenated CAR-T cells.

With the IND clearance, Oricell is now authorized to commence clinical development for OriCAR-017 in the United States without delay.

The single-arm, open-label, dose-escalation study is evaluating the safety, tolerability, cellular kinetics, and initial efficacy of OriCAR-017 among patients with multiple myeloma who have failed the standard treatments^.2

Enrollment in the study was open to patients aged 18-75 with a life expectancy longer than 12 weeks, an ECOG performance status of ≤ 2, and multiple myeloma diagnosed according to the IMWG standard in 2018. E​​xpression of GPRC5D in bone marrow plasma cells must be more than 20% or be positive in tumor tissue by immunohistochemistry, have received at least 3 different mechanism drugs, have failed treatments, or have progressed or recurred during the last treatment or within 6 months after the end of treatment, and have normal lung function with oxygen saturation greater than 92%. Further, patients must have an echocardiogram that showed normal diastolic function, left ventricular ejection fraction ≥50%, no serious arrhythmia, adequate liver and renal function, and must not have heart disease or coronary heart disease.

The primary end points of the study are dose-limiting toxicities, adverse events, and serious adverse events. Secondary end points include concentration of CAR-T cells, ORR, disease control rate, duration of remission, progression-free survival, and overall survival.

REFERENCES:

1. ​​Oricell announces FDA clearance of IND application for OriCAR-017, a novel GPRC5D targeted CAR-T cell therapy utilizing the company's proprietary platform, for the treatment of relapsed/refractory multiple myeloma. News release. Oricell Therapeutics. January 29, 2024. Accessed January 29, 2024. http://tinyurl.com/4kh3d7sm

2. A study of CAR-T cells targeting GPRC5D in the treatment of r/​r multiple myeloma. ClinicalTrials.gov. Updated November 1, 2022. Accessed January 24, 2024. https://clinicaltrials.gov/study/NCT05016778?tab=table