Universal BCMA-targeted LUCAR-B68 Cells in Patients With Relapsed/Refractory Multiple Myeloma

A Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Universal BCMA-targeted LUCAR-B68 Cells Product in Patients With Relapsed/Refractory Multiple Myeloma

A Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Universal BCMA-targeted LUCAR-B68 Cells Product in Patients With Relapsed/Refractory Multiple Myeloma

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Biological: LUCAR-B68 cells product

Detailed Description

This is a prospective, single-arm, open-label, dose-finding and dose-expansion study that evaluates the safety, tolerability, PK, and anti-tumor efficacy of LUCAR-B68 cell preparations in relapsed/refractory multiple myeloma subjects who received adequate standard therapy

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wan-Hong Zhao, PhD; Phone Number: 86-29-87679459; Email: zhaowanhong68@163.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Second Affiliated Hospital of Xi'an JiaoTong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject voluntarily participates in the clinical study; Fully understand and be Informed of the study and sign the Informed consent (Informed Consent Form, ICF); Willing to follow and able to complete all test procedures; Informed consent must be obtained before initiating any tests or procedures related to the study that are not part of the standard treatment of the subject's disease;
2. Subjects ≥ 18 years of age.
3. Eastern Cooperative Oncology Group performance status score of 0, 1, or 2;
4. Documented initial diagnosis of MM according to IMWG diagnostic criteria.
5. Presence of measurable disease at screening.
6. Received a PI and an IMiD (except thalidomide).
7. Received at least 3 prior lines of therapy for multiple myeloma, undergone at least 1 complete cycle of treatment for each line, unless progressive disease (PD) was documented by IMWG criteria as the best response to the regimen. Also, subjects refractory or intolerant to any PI and any IMiD in their previous treatment afterwards are eligible.
8. Expected survival ≥ 3 months.
9. Clinical laboratory values meet screening visit criteria
10. Fertile women must be negative using a highly sensitive serum pregnancy test (β human chorionic gonadotropin [β -HCG]) at screening time and before initial treatment with cyclophosphamide and fludarabine;

Exclusion Criteria:

1. No response to prior BCMA-targeted CAR-T therapy (except in subjects who relapsed after CR to prior CAR-T treatment);
2. Prior treatment with any antibody targeting BCMA;
3. Known active, or prior history of central nervous system (CNS) involvement, or clinical signs of membrane/spinal membrane involvement of multiple myeloma;
4. Serious underlying medical conditions
5. Positive of any hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), human immunodeficiency virus antibody (HIV-Ab) at the time of screening;
6. Male subjects who have a birth plan during the study period or within 1 year after the study treatment
7. Female subjects who are pregnant, breast-feeding, or plan to become pregnant during the study period or within 1 year after the study treatment
8. The investigator considered that the subjects were not suitable for any conditions of participation in the study

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: LUCAR-B68 cells product; Each subject will receive LUCAR-B68 cells	Biological: LUCAR-B68 cells product; Before treatment with LUCAR-B68 cells, subjects will receive a conditioning regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)	An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment	Minimum 2 years after LUCAR-B68 infusion (Day 1
Dose-limiting toxicity (DLT) rate	Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose	Minimum 2 years after LUCAR-B68 infusion (Day 1)
Recommended Phase 2 dose (RP2D) finding	RP2D established through ATD+BOIN design	30 days after LUCAR-B68 infusion (Day 1)
CAR positive NK cells in peripheral blood and bone marrow	CAR positive NK cells in peripheral blood and bone marrow after LUCAR-B68 infusion	Minimum 2 years after LUCAR-B68 infusion (Day 1)
CAR transgene levels in peripheral blood	CAR transgene levels in peripheral blood after LUCAR-B68 infusion	Minimum 2 years after LUCAR-B68 infusion (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The ORR is defined as the percentage of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria	Minimum 2 years after LUCAR-B68 infusion (Day 1)
Duration of Response (DOR)	Duration of response (DOR) will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria or death due to any cause, whichever occurs first	Minimum 2 years after LUCAR-B68 infusion (Day 1)
Time to Response (TTR)	Time to response (TTR) is defined as the time between date of the initial infusion of LCAR-B38M CAR-T cells and the first efficacy evaluation that the participant has met all criteria for PR or better	Minimum 2 years after LUCAR-B68 infusion (Day 1)
Progress Free Survival (PFS)	Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LUCAR-B68 to the first documented disease progression (according to IMWG criteria) or death (due to any cause), whichever occurs first	2 years after LUCAR-B68 infusion (Day 1)
Overall Survival (OS)	Overall Survival (OS) is defined as the time from the date of first infusion of LUCAR-B68 to death of the subject	Minimum 2 years after LUCAR-B68 infusion (Day 1)
Incidence of anti- LUCAR-B68 antibody	Venous blood samples will be collected to measure LUCAR-B68 positive cell concentrations and the transgenic level of LUCAR-B68, at the time points when anti- LUCAR-B68 antibody serum samples are evaluated	Minimum 2 years after LUCAR-B68 infusion (Day 1)

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
• Collaborators: Nanjing Legend Biotech Co.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): March 1, 2027

Study Registration Dates

• First Submitted: August 10, 2022
• First Submitted That Met QC Criteria: August 10, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: BM2L202201

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