OriCAR-017 Demonstrates Durable and Deep Responses in Heavily Pretreated Relapsed/Refractory Multiple Myeloma: Two-Year Follow-Up Data from Phase 1 POLARIS Trial

On June 5, 2024, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Qrigincell Therapeutics presented the 2-year long-term follow-up results of its self-developed GPRC5D-targeted CAR-T cell injection (OriCAR-017) in the treatment of relapsed/refractory multiple myeloma (RRMM) from a Phase I clinical trial in an oral report. The data showed that OriCAR-017 still demonstrated significant and durable efficacy in RRMM patients who had failed multiple treatments, while maintaining good safety and tolerability.

Efficacy and Durability Assessment

Data as of January 16, 2024, showed that OriCAR-017 demonstrated deep and durable responses in RRMM patients who had failed treatment with anti-CD38, proteasome inhibitors (PI), immunomodulatory drugs (IMiDs), and BCMA CAR-T therapy. All (10) patients responded well to OriCAR-017 treatment, with the last patient completing 24 months of efficacy observation. The overall response rate (ORR) was 100.0%, the stringent complete response rate (sCR) was 80.0%, and the very good partial response rate (VGPR) was 20.0%. All patients achieved a 100% minimal residual disease-negative rate (MRD) by Day 28, which was further confirmed at Month 3 as 100% negative. The median duration of response (mDoR) was 10.43 months (95% CI, 5.00-17.00), the median progression-free survival (mPFS) was 11.37 months (95% CI, 5.93-18.00), and the median overall survival (mOS) has not yet been reached (seven patients are still in survival follow-up, one patient died from disease progression, and two patients died from COVID-19 infection). In the high-dose group (2/3 were BCMA CAR-T pretreated patients), the mDoR was 17.23 months (95% CI, 7.33-NR), and the mPFS was 19.10 months (95% CI, 8.30-NR). Currently, one BCMA CAR-T pretreated patient is still in ongoing remission (>24 months).

The long-term efficacy and safety follow-up results further demonstrate that OriCAR-017 has the potential to become a new treatment option for RRMM patients. Currently, the registration clinical trials of OriCAR-017 are proceeding smoothly in both China and the United States (China NCT06182696; United States NCT06271252).

Safety and Tolerability Evaluation

Nine patients (90%) experienced Grade 1 cytokine release syndrome (CRS), with only one patient (10%) developing Grade 2 CRS. No instances of Grade ≥3 CRS were observed. The median onset time for CRS was 2 days (range: 1–9 days), with a median duration of 6 days (range: 3–9 days). No immune effector cell-associated neurotoxicity syndrome (ICANS) or dose-limiting toxicity (DLT) was observed. There were no serious adverse events (SAEs) or treatment-related deaths, and no reports of cerebellar disease or related neurotoxicity were noted. Additionally, no delayed infections occurred.

Pharmacokinetics and GPRC5D Expression Analysis

Long-term follow-up data revealed no pharmacokinetic differences between dose levels, with a Cmax of 7354.7 copies/μL and an AUC0-28 days of 68587 copies•day/μg. At higher doses, CAR-T cells were still detectable at 9 months; after 21 months of follow-up, one patient's CAR-T cell expansion remained above the lower limit of quantification (LLOQ). Patients with Tlast ≥ 9 months exhibited longer progression-free survival compared to those with Tlast < 9 months. Baseline data from all patients showed positive GPRC5D expression in bone marrow CD138+ plasma cells (MMPC), with 50% of relapsed patients showing downregulated expression as detected by flow cytometry. Notably, no correlation was clinically observed between antigen expression and therapeutic efficacy or prior BCMA CAR-T treatment.

The Application Potential of OriCAR-017 in Very Late-stage RRMM Patients

Notably, the baseline conditions of these enrolled patients were relatively advanced. Among them, 80% were ISS stage II or III, 70% had high-risk cytogenetic abnormalities, 70% had an ECOG score of 2, 50% had received one or more CAR-T treatments targeting BCMA, and 40% had extramedullary lesions (EMD). Additionally, three cases (30%) were treated with BCMA and had EMD. These data further demonstrate the application potential of OriCAR-017 in patients with extremely advanced baseline conditions.

2024 ASCO Annual Meeting Oral Presentation Information

Oral presentation #7511
Title: OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS).
Session Type: Rapid Oral Abstract Session
Session Title: Hematologic Malignancies—Plasma Cell Dyscrasia
Link:https://meetings.asco.org/abstracts-presentations/239043

About OriCAR-017

OriCAR-017, a chimeric antigen receptor (CAR) T-cell therapy targeting GPRC5D, offers new hope for patients with relapsed/refractory multiple myeloma. The therapy is based on QrigincellTherapeutics' self-developed technology platform and demonstrates excellent performance in terms of cell affinity, antigen-binding activity and persistence, anti-tumor efficacy, and safety. After receiving IND approval from China’s National Medical Products Administration (NMPA), OriCAR-017 further obtained IND approval from the U.S. FDA in January 2024.

Currently, Qrigincell Therapeutics has established operational teams in both China and the United States, and is fully committed to advancing the global clinical development of its product pipeline.

Editorial Responsibility: Mu Mian

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