SG301 Safety Study in Subjects With Relapsed or Refractory Multiple Myeloma and Other Hematological Malignancies

Study Overview
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Brief Summary
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This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy in patients with relapsed or refractory multiple myeloma and other hematological malignancies

Detailed Description
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Duration of dose limiting toxicity (DLT) observation is 28 days

Official Title
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A First-in-human Phase 1 Study to Evaluate Safety, Tolerability, and Preliminary Efficacy of SG301 in Subjects With Relapsed or Refractory Multiple Myeloma and Other Hematological Malignancies

Conditions
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Relapsed or Refractory Multiple Myeloma, Hematological Malignancy

Intervention / Treatment
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* Drug: SG301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet all the following criteria to be eligible for participation in this study: Able to understand, voluntarily participate in and willing to sign the ICF. Male or female subject ≥ 18 years. Histologically or cytologically confirmed hematologic malignancy that has relapsed or is refractory to standard therapy and has exhausted all available therapies or rejects other therapy. For Part 1, the expression of CD38 in subjects will be tested, but not necessarily required to be positive in order to enroll; patients with CLL and indolent NHL should have disease that requires treatment. For Part 2, NHL and HL must be CD38+ confirmed with a validated method. Subjects are able to follow the study protocol and complete the trial. Presence of measurable or evaluable disease. Must have adequate organ function, prior to start of SG301, including the following: Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.0 ×109/L without growth factor support within 7 days prior to entry (no ANC requirement for patients with acute leukemia; ANC ≤20×109/L for leukemias, except for CLL where an elevated WBC count will not exclude patients from study entry); platelet count ≥ 75 × 109/L without transfusion within 7 days prior to entry; hemoglobin ≥ 8 g/dL or ≥ 5.6 mmol/L without transfusion within 7 days prior to entry; Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × ULN. Renal: serum creatinine ≤1.5 times the ULN or estimated creatinine clearance ≥50 mL/min (Cockroft and Gault formula [http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/]). Coagulation tests INR≤ 2 or prothrombin time ≤ 2×ULN. Left ventricular ejection fraction (LVEF) ≥50% measured by ECHO or MUGA (only if ECHO not available) or lower limit for institutional normal value. Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy Subjects (women of child-bearing potential and males with fertile female partner) must be willing to use currently accepted reliable contraception method throughout the treatment period and for at least three months following the last dose of study drug. These measures include, but are not limited to, oral or implantable injections of hormonal contraceptives; intrauterine birth control ring or placement of IUS intrauterine device); or use of barrier methods such as condoms or septum and spermicide products. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing age must have a negative pregnancy test. ECOG score<2 for dose escalation part, and ECOG ≤ 2 for dose expansion part; life expectancy ≥3 months. Exclusion Criteria: Subjects must not have any of following: Participated in any experimental treatment of any diseases within 4 weeks prior to entry. Prior therapy with other monoclonal antibodies targeting the CD38 antigen or prior therapy with other IgG monoclonal antibodies within 3 months prior to first study treatment, or IgM monoclonal antibodies within 1 month prior to first study treatment. Received any other anti-tumor drug therapies within 5 half-lives, or 4 weeks, whichever is shorter. Known history of a Grade 3-4 allergic reaction to treatment with any humanized products. Patients with symptomatic or untreated CNS metastases, or those requiring ongoing treatment for CNS metastases, including steroids and antiepileptic agents. Pregnant or nursing females. History of life-threatening hypersensitivity, or known to be allergic to protein drugs or recombinant proteins or excipients in SG301 drug formulation. Peripheral neuropathy ≥ Grade 3. Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer< 1000 cps/mL or 200 IU/mL), or cured Hepatitis C (negative HCV RNA test) may be enrolled. Subjects with known positive HIV status. Active infection requiring intravenous therapy within 2 weeks prior to entry. Known severe chronic obstruction respiratory disease or asthma defined FEV1% < 60% predicted. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia). Uncontrolled hypertension (systolic blood pressure >150 mmHg and diastolic blood pressure >100 mmHg), a history of hypertension crisis, or a history of hypertensive encephalopathy. Received allogeneic stem cell transplantation within 3 months prior to entry, or GVHD after allogeneic stem cell transplantation requiring systemic immunosuppressants, such as cyclosporin or tacrolimus. Concurrent malignancy within 2 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer under active surveillance. Major surgery within 4 weeks prior to study entry; Minor surgery within 2 weeks prior to study entry. Intolerant to IV infusion. Any condition that the Investigator or primary physician believes may not be appropriate for participating the study. Excluding subject who was treated with corticosteroid exceeding 15mg/day of prednisone or equivalent in the last 2 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SG301<br>Study treatment: SG301 administered every week via intravenous infusion | Drug: SG301<br>* During study treatment, subjects will receive SG301 treatment via IV infusion once every week at doses of 0.01, 0.03, 0.1, 0.3, 1.0, 2.0, 4.0, 8.0, 12.0 and 16.0mg/kg<br>* Other names: An IgG1κ human monoclonal antibody (mAb) that binds to CD38;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with AEs and SAEs | To evaluate the safety and tolerability of SG301 [Adverse events (AEs), Serious Adverse Events (SAE) ] | At the end of treatment phase (24 weeks) | 
| The Maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) for SG301 | It will be determined based on safety, tolerability, pharmacokinetics, preliminary efficacy, and other available data by pooling and evaluating all available target attainment/engagement data, clinical PK, PD, tolerability and safety data to select the appropriate dose | At the end of treatment phase (24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): AUC | The area under the curve (AUC) of serum concentration of the drug after the administration | Approximately 2 years | 
| Pharmacokinetics (PK): Cmax | Maximum concentration(Cmax) of the drug after administration | Approximately 2 years | 
| Preliminary anti-tumor activity of SG301 (Objective Response Rate) | Objective response to according to IMWG response criteria for MM, Lugano criteria for lymphoma, and other standard criteria for other hematologic malignancies | Approximately 2 years | 
| Immunogenicity: percentage of ADA positive patients | Number of Anti-Drug Antibodies (ADA) positive patients will be counted and percentage of ADA positive patients will be calculated to evaluate immunogenicity of SG301 | Approximately 2 years |