Blood Protein Disorders, Cardiovascular Diseases, Hematologic Diseases, Hemorrhagic Disorders, Hemostatic Disorders, Immune System Diseases, Immunoproliferative Disorders, Lymphoproliferative Disorders, Multiple Myeloma, Neoplasms, Neoplasms by Histologic Type, Neoplasms, Plasma Cell, Paraproteinemias, Vascular Diseases
Conditions
Keywords
R/R MM, CAR-T
Brief summary
The is a first clinical study for Oricell Therapeutics Inc. in the United States to evaluate the safety, PK, PD and preliminary efficacy of our anti-GPRC5D cell product (OriCAR-017) in subjects with relapsed/refractory multiple myeloma. RIGEL Study
Detailed description
This is a Phase I/II, open-label multicenter study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of anti-GPRC5D CAR-T cell product (OriCAR-017) in subjects with relapsed/refractory multiple myeloma. The study will consist of a Phase I dose escalation stage involving three doses as a single IV infusion) with up to 18 evaluable subjects and a dose expansion stage with 10-15 evaluable subjects, followed by a Phase II stage with up to 48 evaluable subjects.
Interventions
DRUGOriCAR-017
Anti-GPRC5D CAR-T cell product
Sponsors
OriCell Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Capable of giving signed informed consent Subjects aged 18 to 75 years (inclusive) at Screening (signing the ICF). Expected survival period is \>12 weeks. Diagnosis of MM according to the IMWG criteria (2016 version). One of the following criteria must be met: If immunoglobulin (Ig)G type MM, then serum M protein \>10 g/L; if IgA, IgD, IgE or IgM type MM, then serum M protein \>5 g/L Urine M protein level \>200 mg/24 hour If light chain type MM, then serum free light chain (sFLC) \>100 mg/L and K/λ FLC ratio is abnormal. Extramedullary lesions (\>1 cm for diameter of the short axis). For Phase I (dose-escalation) - Subjects who had received at least 3 prior lines of therapy, had previous exposure to BCMA-Ag+ therapies, and were refractory to the last line of therapy. For Phase I (dose-expansion) and Phase II: Subjects with previous exposure to BCMA directed therapies including BCMA bispecific antibody (e.g., teclistamab), BCMA antibody directed conjugate (such as BLENREP), and BCMA-CAR-T (such as CARVYKT1TM) Subjects with adequate hematologic, renal, hepatic, pulmonary and cardiac function. Subject and partners willing to take and or use effective contraceptive measures until 2 years post IMP infusion.
Exclusion criteria
Pregnant or breastfeeding. Seropositive for history of human immunodeficiency virus Active Hepatitis B infection and or Hepatitis C infection Known active or prior history of CNS involvement History of autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs or required systemic application of immunosuppressive or other drugs in the past 2 years Presence of uncontrolled active infection Subjects who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks of Screening Visit or who plan to undergo ASCT during the study. Subjects who received allogeneic stem cell therapy. Any condition that in the opinion of the Investigator, would interfere with evaluation of the IMP. Received Bendamustine treatment 1 year prior to Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) of OriCAR-017 US-P1 | Up to 28 days | The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. |
| Dose-limiting toxicity (DLT) | Up to 28 days | A DLT is defined as any of the treatment-emergent adverse events (TEAEs; a TEAE is defined as an adverse event \[AE\] that starts on or after the first administration of study medication) condition or concomitant medications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Duration of Response (DOR) of treatment in patients with RR/MM | Up to 2 years | DOR as assessed by Local Investigators according to the IMWG Criteria |
| Progress-Free Survival (PFS) of treatment in patients with RR/MM | Up to 2 years | PFS as assessed by Local Investigators according to the IMWG Criteria |
| Assessment of Overall Survival (OS) of treatment in patients with RR/MM | Up to 2 years | OS as assessed by Local Investigators according to the IMWG Criteria |
| Evaluate PK parameters of OriCAR-017 in subjects with relapsed/refractory MM | Up to 2 years | Assess concentration of CAR-T cells in peripheral blood |
| Assessment of Overall Response Rate (ORR) | Up to 2 years | Percentage of subjects with PR, + VGPR+ CR + strict complete response (sCR) as assessed by Local Investigator according to the IMWG criteria |
| Assessment of Disease Control Rate (DCR) | Up to 2 years | Percentage of subjects with CBR (Clinical Benefit Rate) + Stable Disease as assessed by Local Investigator according to IMWG Criteria |
| Assessment of Clinical Benefit Rate (CBR) | Up to 2 years | Percentage of subjects with ORR + Minimal Response by Local Investigator according to IMWG Criteria |
| Assessment of MRD negative Rate | Up to 2 years | Proportion of subjects with MRD negative status by flow cytometry |
| Evaluate PD parameters of OriCAR-017 in subjects with relapsed/refractory MM | Up to 2 years | Assess PD markers related to CAR-T therapy in peripheral blood. |
Countries
United States
Outcome results
None listed