Study of the Safety and Efficacy of STI-6129 in Patients With Relapsed or Refractory Systemic AL Amyloidosis

Inclusion Criteria:

• Confirmed diagnosis of AL amyloidosis by tissue biopsy of an involved organ, or asurrogate site such as abdominal fat demonstrating amyloid deposition by massspectrometry
• The presence of a monoclonal light chain protein in serum
• Relapsed or refractory AL amyloidosis is defined as patients who have received ≥ 2lines of treatment. Patients must have received at least one proteasome inhibitorduring their prior therapy. Patients who have received prior daratumumab treatment orprior stem cell transplantation remain eligible. Patients may have relapsed withdisease progression or have been refractory to their last prior line of treatment.Progression of disease that develops > 60 days after the last dose of a treatmentregimen in a patient who achieved at least a partial response (PR) defines a relapse.Refractory systemic AL amyloidosis is defined as the development of diseaseprogression during therapy with an anti-AL amyloidosis treatment regimen or within 60days of the last dose of an anti-AL amyloidosis treatment regimen or the achievementof less than a PR after ≥ 2 cycles
• Measurable disease defined as the finding by serum-free light chain (FLC) assay thatthe difference between the involved and uninvolved FLC (dFLC) is ≥ 50 mg/L
• Pulse oximetry ≥ 92% on room air
• ECOG performance status of 0, 1, or 2
• Willing to comply with the study schedule and all other protocol requirements
• Females of childbearing potential (FCBP) must have 2 negative pregnancy tests prior totreatment. All heterosexually active FCBP and all heterosexually active male patientsmust agree to use effective methods of birth control throughout the study

Exclusion Criteria:

• Isolated vascular amyloid in a bone marrow biopsy or a plasmacytoma specimen orisolated soft tissue involvement (localized AL amyloidosis)
• Presence of non-AL amyloidosis
• A diagnosis of multiple myeloma
• A diagnosis of other malignancies if the malignancy has required therapy within thelast 3 years or is not in complete remission. Exceptions are non-metastatic basal cellor squamous cell carcinomas of the skin or prostate cancer that does not requiretreatment
• Treatment with an allogeneic hematopoietic stem cell transplantation (HSCT) within 6months prior to the planned infusion of STI-6129, or active graft-versus-host disease (GVHD) following the allogeneic transplant, or a requirement for currently receivingimmunosuppressive therapy following the allogeneic transplant
• Revised Mayo Clinic AL amyloidosis stage > 3
• New York Heart Association (NYHA) class > 2
• Left ventricular ejection fraction (LVEF) < 40%
• Patients with mean left ventricular wall thickness ≥ 12 mm and/or intraventricularseptal thickness > 25 mm by echocardiogram in the absence of hypertension or valvularheart disease
• Patients with NT-proBNP ≥ 1800 ng/L or BNP ≥ 400 ng/L, or cTNT ≥ 0.025 μg/L will beexcluded in the dose-escalation stage of the study and can only be included in the PKand expansion stages after evaluation by cardiology and discussion with the principleinvestigator regarding the risk associated with the treatment
• Abnormal baseline hematological laboratory results at Screening:
• Hemoglobin < 8.0 g/dL
• Platelet count < 50,000/μL
• Absolute neutrophil count (ANC) < 1000/μL
• Abnormal baseline chemistry laboratory results at Screening:
• Serum creatinine ≥ 2.0 mg/dL or estimated creatinine clearance < 60 mL/min (usingthe Cockcroft-Gault equation)
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x theupper limit of normal (ULN) or serum total bilirubin > 1.5x ULN (except forpatients in whom hyperbilirubinemia is attributed to Gilbert's Syndrome)
• INR or aPTT > 1.5x ULN within 1 week prior to the infusion of STI-6129, unless on astable dose of an anticoagulant
• Pregnant or breastfeeding
• Active bacterial, viral, or fungal infection within 72 hours of the infusion ofSTI-6129; patients with ongoing use of prophylactic antibiotics, antifungal agents, orantiviral agents remain eligible as long as there is no evidence of active infection
• Have human immunodeficiency virus (HIV) infection, human T-cell leukemia virus type 1 (HTLV1) infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia orare at risk for HBV reactivation (at risk for HBV reactivation is defined as being HBsantigen positive, or anti-HBc-antibody positive), or are positive for HBVdeoxyribonucleic acid (DNA). HCV ribonucleic acid (RNA) must be undetectable bylaboratory test
• QTcF > 470 msec on a baseline ECG
• Any condition including the presence of laboratory abnormalities that places thepatient at unacceptable risk if the patient was to participate in the study