Study of Naive HBI0101 CAR-T Therapy in Relapsed/Refractory Multiple Myeloma

Inclusion criteria

• ≥18 years of age at the time of signing informed consent.
• Voluntarily signed informed consent form.
• Diagnosis of relapsed/refractory multiple myeloma (Parts 1a and 1b), with measurable disease at screening visit as follows:

Multiple Myeloma (at least one of the criteria below):

• Serum M-protein greater or equal to 0.5 g/dL.
• Urine M-protein greater or equal to 200 mg/24 h.
• Serum free light chain (FLC) assay: involved FLC level greater or equal to 3 mg/dL (30 mg/L) provided serum FLC ratio is abnormal.
• A biopsy-proven evaluable plasmacytoma*.
• Bone marrow plasma cells > 10% of total bone marrow cells*.
• Non secretory patient will be allowed provided they have measurable disease by PET-CT or bone marrow aspiration, as designated*.

• Results pre-dating the Screening visit by up to 28 days may be used to establish eligibility.
• R/R MM subjects must have been exposed to at least three prior lines of therapy including the following agents:

• proteasome inhibitor
• immunomodulatory (IMiDs) agent
• anti-CD38 antibody
• For part 1a: At least one of the following risk factors: a. Extra-medullary disease (EMD) - defined as a MM lesion that is not connected to a bone. b. previous exposure to an anti-BCMA therapy.
• 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, and toxicities that are irreversible and not expected to interfere with study treatment or pose safety concerns, per investigator judgement.
• Ability and willingness to adhere to the study visit schedule and all protocol requirements.
• For subjects with relapsed multiple myeloma who have previously undergone allogenic stem cell transplantation: 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/or direct bilirubin > 4x ULN.
• Inadequate renal function defined by 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/mm3, platelet count < 30,000 mm3, or hemoglobin < 8 g/dL. Subjects with absolute lymphocyte count < 300 cells/mm3 may be excluded (due to potential challenges with producing CART), per investigator judgement.
• 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/m2/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 active infection (defined as HBS-antigen and HBV DNA positive) or Hepatitis C active infection (defined as anti-HCV and HCV RNA positive).
• 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 malignancy that has required therapy in the last 2 years or is not in complete remission. This exclusion criterion does not exclude the following subjects: successfully treated non- metastatic basal cell or squamous cell skin carcinoma, or prostate cancer under control with hormonal therapy
• 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.