Study of HBI0101 (NXC-201) CAR-T Therapy in Multiple Myeloma and Light-Chain Amyloidosis

Up to 180 subjects with relapsed/refractory (R/R) multiple myeloma (MM) or light chain amyloidosis (AL) will be enrolled in a single-arm, open-label, single-site Phase 2 study. Eligible subjects will undergo leukapheresis procedure to provide starting material for manufacturing of HBI0101 CART investigational product. Each eligible subject will receive a single dose of HBI0101 CART cells. Prior to administration of HBI0101 CART, the study subjects will undergo lymphodepletion. Following administration of HBI0101 CART the subjects will be hospitalized for several days and then will return for routine follow-up periodical visits until 24 months after infusion.

Inclusion criteria

• ≥18 years of age at the time of signing informed consent.
• Voluntarily signed informed consent form.
• Diagnosis of multiple myeloma and/or light-chain amyloidosis with relapsed or refractory disease, with measurable disease at screening visit
• Subject suffering from multiple myeloma must have been exposed to at least two prior lines of therapy including proteasome inhibitor, immunomodulatory (IMiDs) therapy or anti-CD38 antibody, or functionally high-risk patients (i.e. first relapse within 18 months of treatment initiation) may be included.

Subject with amyloidosis must have been exposed to at least one prior line of therapy which includes proteasome inhibitor or anti-CD38 antibody, or subjects with insufficient response (i.e. not achieving a VGPR or CR after exposure to at least an anti-CD38 antibody and a proteasome inhibitor) may be included.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study.
• Recovery to ≤ Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy.
• Ability and willingness to adhere to the study visit schedule and all protocol requirements.
• Subjects with relapsed multiple myeloma who have previously undergone allogenic stem cell transplantation must have no evidence of graft versus host disease after cessation of any immunosuppressive therapy for at least one month before recruitment to the study.

Exclusion criteria

• Contraindication to a study treatment/procedure or is anticipated to receive treatment/procedure that may preclude performance of study procedures.
• Known bulky central nervous system disease.
• Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN) and direct bilirubin > 4x ULN.
• Inadequate renal function defined by serum creatinine clearance/estimated clearance of <20(ml/min).
• International ratio (INR) or partial thromboplastin time (PTT) > 2 x ULN, unless on a stable dose of anticoagulant for a thromboembolic event (provided this event is not an exclusion criteria).
• Inadequate bone marrow function defined by absolute neutrophil count (ANC) < 1000 cells/mm^3, platelet count < 30,000 mm^3, or hemoglobin < 8 g/dL. Subjects with absolute lymphocyte count < 300 cells/mm^3 may be excluded (due to potential challenges with producing CART cells), per investigator judgement.
• Echocardiogram with left ventricular ejection fraction < 40%.
• Ongoing treatment with chronic immunosuppressant such as cyclosporine or systemic steroids (physiological replacement doses of steroids are allowed up to 12 mg/m^2/d hydrocortisone or equivalent)
• Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions.
• Known human immunodeficiency virus (HIV) positive status.
• Active Hepatitis B or Hepatitis C active infection.
• Active CMV infection.
• Known history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 3 months.
• Chronic atrial fibrillation with uncontrolled heart rate.
• Second primary malignancies that has required therapy in the last 2 years or is not in complete remission.
• Subjects who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation and who meet any of the following criteria:

• Have been on a stable dose of anticoagulation for < 1 month (except for acute line insertion induced thrombosis.)
• Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days
• Are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement).
• Pregnant or lactating women.
• Participation in another interventional clinical trial within 30 days prior to screening visit.