Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of IBI346#CIBI346Y002#

Study Overview
=================
Brief Summary
-----------------
An open label, single-arm clinical study evaluating the safety and efficacy of IBI346 infusion in relapsed/refractory multiple myeloma

Official Title
-----------------
An Open, Single-arm Clinical Study Evaluating the Safety and Efficacy of IBI346 Infusion in Relapsed/Refractory Multiple Myeloma

Conditions
-----------------
Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: IBI346


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: According to the multiple myeloma diagnostic criteria of the International Myeloma Working Group (IMWG), there is the initial diagnosis of multiple myeloma. Subjects must have previously received at least 3 anti-myeloma regimens. Subjects must have documented disease progression (according to IMWG criteria) during or within 12 months of completing their last anti-myeloma regimen prior to study entry; and prior regimens must have included proteasome inhibitor (PI) and immunomodulatory drug (IMiD). Measurable disease as defined by the protocol ECOG score is 0 or 1. Expected survival time ≥12 weeks. Exclusion Criteria: Patients suffering from graft-versus-host disease (GVHD) or requiring immunosuppressants drugs. Patients who received autologous hematopoietic stem cell transplantation (ASCT) or prior allogeneic hematopoietic stem cell transplantation (ALLo-HSCT) within 12 weeks prior to mononuclear cell collection. No unmobilized mononuclear cells can be collected for CAR T cell production. Screening subjects who were receiving systemic steroids during the previous 7 days or who were determined by the investigator to require long-term systemic steroid use during treatment (except for inhaled or topical use, except at doses < 10mg/ day). Patients with a history of hypertension that cannot be controlled by medication (blood pressure ≥140/90 mmHg).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI346<br>Single arm | Drug: IBI346<br>* IBI346 Antibody and IBI346 CAR-T cell injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) |  | 21 days post IBI346 administration | 
| Incidence and severity of adverse events: Proportion of subjects with treatment-related adverse events assessed by NCI-CTCAE v5.0 criteria |  | 2 years post IBI346 administration | 
| Presence or absence of replication-competent lentivirus (RCL) |  | Baseline up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Number of patients with a best response of either complete response, stringent complete response, very good partial response or partial response, assessed using modified International Myeloma Working Group response criteria（2016） | 3 months post IBI346 administration | 
| Duration of Response (DOR) | DOR will be calculated among responders (with a PR or better response) from the date of initial response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria (2016). | 2 years post IBI346 administration | 
| Progression-free Survival (PFS) | PFS defined as time from date of initial administration of IBI346 to date of first disease progression according to IMWG criteria (2016), or death due to any cause, whichever occurs first. | 2 years post IBI346 administration | 
| Overall Survival (OS) | OS is measured from the date of the initial administration of IBI346 to the date of the subject's death. | 2 years post IBI346 administration | 
| Pharmacokinetics parameters of IBI346 cells -Maximum CAR level in blood (Cmax) |  | 2 years post IBI346 administration | 
| Pharmacokinetics parameters of IBI346 cells -Time to peak CAR level in blood (Tmax) |  | 2 years post IBI346 administration | 
| Pharmacokinetics parameters of IBI346 cells - Area under the curve of the CAR level in blood (AUC) |  | 2 years post IBI346 administration | 
| Pharmacokinetics parameters of IBI346 antibody- Peak Plasma Concentration (Cmax) |  | 2 years post IBI346 administration | 
| Pharmacokinetics parameters of IBI346 antibody- Area under the plasma concentration versus time curve (AUC) |  | 2 years post IBI346 administration | 
| Pharmacokinetics parameters of IBI346 antibody- clearance (CL) |  | 2 years post IBI346 administration | 
| Pharmacokinetics parameters of IBI346 antibody- half-life (t1/2) |  | 2 years post IBI346 administration | 
| Pharmacodynamics characteristics - Cytokines Concentrations, cytokines level and the content of soluble BCMA in blood |  | 2 years post IBI346 administration |