A Study to Evaluate the Safety, PK/PD of (OriCAR-017) in Subjects With RR/MM - RIGEL Study

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 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

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Vascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemostatic Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Paraproteinemias; Blood Protein Disorders
• Intervention / Treatment: Drug: OriCAR-017

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.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Northside Hospital
      • Contact: Melhem Solh; Phone Number: 404-255-1930; Email: msolh@bmtga.com
      • Contact: Caitlin Guzowski; Phone Number: 4042551930; Email: caitlin.guzowski@northside.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OriCAR-017; Single OriCAR-017 infusion	Drug: OriCAR-017; Anti-GPRC5D CAR-T cell product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of OriCAR-017 US-P1	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.	Up to 28 days
Dose-limiting toxicity (DLT)	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.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate PK parameters of OriCAR-017 in subjects with relapsed/refractory MM	Assess concentration of CAR-T cells in peripheral blood	Up to 2 years
Evaluate PD parameters of OriCAR-017 in subjects with relapsed/refractory MM	Assess PD markers related to CAR-T therapy in peripheral blood.	Up to 2 years
Assessment of Duration of Response (DOR) of treatment in patients with RR/MM	DOR as assessed by Local Investigators according to the IMWG Criteria	Up to 2 years
Progress-Free Survival (PFS) of treatment in patients with RR/MM	PFS as assessed by Local Investigators according to the IMWG Criteria	Up to 2 years
Assessment of Overall Survival (OS) of treatment in patients with RR/MM	OS as assessed by Local Investigators according to the IMWG Criteria	Up to 2 years
Assessment of MRD negative Rate	Proportion of subjects with MRD negative status by flow cytometry	Up to 2 years
Assessment of Overall Response Rate (ORR)	Percentage of subjects with PR, + VGPR+ CR + strict complete response (sCR) as assessed by Local Investigator according to the IMWG criteria	Up to 2 years
Assessment of Disease Control Rate (DCR)	Percentage of subjects with CBR (Clinical Benefit Rate) + Stable Disease as assessed by Local Investigator according to IMWG Criteria	Up to 2 years
Assessment of Clinical Benefit Rate (CBR)	Percentage of subjects with ORR + Minimal Response by Local Investigator according to IMWG Criteria	Up to 2 years

Collaborators and Investigators

• Sponsor: OriCell Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2024
• Primary Completion (Estimated): December 12, 2026
• Study Completion (Estimated): April 12, 2028

Study Registration Dates

• First Submitted: January 26, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: R/R MM, CAR-T
• Additional Relevant MeSH Terms: Lymphatic Diseases; Neoplasms; Cardiovascular Diseases; Hemostatic Disorders; Blood Coagulation Disorders; Vascular Diseases; Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Diseases; Hemorrhagic Disorders; Immune System Diseases; Lymphoproliferative Disorders; Neoplasms by Histologic Type; Paraproteinemias; Immunoproliferative Disorders; Blood Protein Disorders
• Other Study ID Numbers: OriCAR-017-US-P1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No