Safety and Efficacy Study of An Anti-CD38 Antibody Drug Conjugate in Relapsed or Refractory Multiple Myeloma
Study Details
Study Description
Brief Summary
This is a phase Ib/IIa, open-label, dose-escalation, and extension study to evaluate the safety and efficacy of an anti-CD38 antibody drug conjugate (STI-6129) in patients with relapsed or refractory multiple myeloma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a phase Ib/IIa, open-label, dose-escalation, and extension study to evaluate the safety and efficacy of an anti-CD38 antibody drug conjugate (STI-6129) in patients with relapsed or refractory multiple myeloma.
The study is designed to identify the recommended phase 2 dose (RP2D) of STI-6129 by assessing the safety, preliminary efficacy and pharmacokinetics using a accelerated titration design and a conventional 3+3 study design for dose escalation in stage one and then the second stage will be an expansion study to assess preliminary efficacy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: STI-6129 Nine dosing cohorts will be evaluated: 0.25 mg/kg，0.50 mg/kg，0.67 mg/kg, 0.88 mg/kg, 1.18 mg/kg, 1.56 mg/kg, 2.08 mg/kg, 2.77 mg/kg, 3.68 mg/kg where STI-6129 will be intravenously administered once as part of a 4-week treatment cycle. |
Biological: STI-6129
Anti-CD38 A2 human antibody drug conjugate (ADC) containing an antibody covalently bound to a duostatin tubulin inhibitor.
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse events（AEs） [Up to 2 years]
Assessing the incidence of adverse events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE Version 5).
- Overall response rate（ORR） [Up to 2 years]
ORR assessed by the modified IMWG response criteria.
Secondary Outcome Measures
- Plasma concentration of the total anti-CD38 antibody [Up to 2 years]
Determine plasma levels of the total antibody.
- Plasma concentration of conjugated toxin [Up to 2 years]
Determine plasma levels of conjugated toxin (STI 6129).
- Plasma concentration of the free toxin [Up to 2 years]
Determine plasma levels of the free toxin (duostatin 5.2).
- Recommended Phase 2 dose (RP2D) [Up to 2 years]
Determined according to the phase 1b.
- Progression-Free Survival [Up to 2 years]
PFS is the period from patient enrollment until PD or death.
- Overall Survival (OS) [Up to 2 years]
OS is the period from enrollment until death from any cause.
- Time To First Response（TTR） [Up to 2 years]
TTR is the period from the date of patient registration to the date of first response.
- Duration of Response (DOR) [Up to 2 years]
DOR is the period from the first documentation of response (CR or PR) to the first documentation of PD.
- Clinical Benefit Rate (CBR) [Up to 2 years]
CBR is the percentage of participants achieving a CR or PR at any time during the study or maintaining stable disease for at least 4 weeks from the first dose of study intervention.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years old, regardless of gender.
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Previously treated with at least three drugs (including PI, IMiD, and anti-CD38 antibody), and relapsed/refractory after the most recent anti-MM therapy.
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Diagnosis of MM according to IMWG criteria with measurable lesions, meeting at least 1 of the following criteria:
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Serum M protein ≥ 0.5g/dL (≥ 5 g/L); or
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Urine M protein ≥ 200mg/24 hours; or
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When the serum free light chain (FLC) ratio is abnormal, the affected FLC level is ≥10mg/dL (≥100 mg/L) (the normal FLC ratio is 0.26 to 1.65).
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ECOG performance status score is 0, 1, or 2.
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Willing and able to comply with the study schedule and all other study protocol requirements.
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Women of childbearing potential (WOCBP) (infertile women are defined as sexually mature females who had undergone a hysterectomy or bilateral oophorectomy or bilateral salpingectomy or bilateral tubal ligation/closure, or who are infertile due to a congenital or acquired condition or spontaneously menopausal for ≥ 12 months) must have a negative blood pregnancy test during the screening. Female subjects of childbearing potential and male subjects with fertility must use a highly effective method of contraception from screening to 6 months after the last treatment.
Exclusion Criteria:
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Known hypersensitivity to any of the ingredients of this product.
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Diagnosis of active plasma cell leukemia.
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Diagnosis of systemic light chain amyloidosis.
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MM involving the central nervous system.
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Has POEMS syndrome.
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There is spinal cord compression associated with MM.
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Needs to take concomitant drugs with a strong inhibitory effect or a strong induction effect on CYP3A4.
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Had received plasma exchange therapy within 28 days before the first administration of the study drug.
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Had received the following anti-tumor treatments before the first administration of the study drug: monoclonal antibody or cytotoxic drug or radiotherapy within 28 days; immunoregulator, targeted therapy or epigenetic therapy or investigational medical product or invasive investigational medical device or other anti-myeloma therapy within 28 days or 5 half-lives (whichever is shorter); proteasome inhibitor or anti-tumor traditional Chinese medicine treatment or corticosteroids with a cumulative dose of more than 140 mg prednisone (or equivalent) or a single dose of more than 40 mg/day dexamethasone (or equivalent) within 14 days.
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Had received CAR-T therapy or allogeneic hematopoietic stem cell transplantation therapy within 6 months before the first administration of the study drug, or have a concomitant disease of active graft-versus-host disease (GvHD) at screening.
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Had received autologous hematopoietic stem cell transplantation within 12 weeks before the first administration of the study drug.
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Had undergone major surgery or eye surgery within 28 days before the first administration of the study drug.
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Other malignant diseases within 3 years before the first administration of the study drug.
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History of grade ≥3 (muscle paralysis, eyelid disease, glaucoma requiring drug control, tearing eyes), or grade ≥2 any other ocular disease (as judged by NCI-CTCAE version 5.0) at screening.
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Has ≥ Grade 3 neuropathy or Grade 2 neuropathy with associated pain.
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The toxicity caused by the previous anti-tumor treatment did not subside to ≤ grade 1.
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Has the following hematological test results within 7 days before the first administration of the study drug:
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Hemoglobin <80g/L
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Platelet count <50×10^9/L
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Absolute neutrophil count <1.0×10^9/L
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Has the following blood chemistry test results within 7 days before the first administration of the study drug:
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Estimated creatinine clearance <30mL/min.
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AST or ALT>3×upper limit of normal (ULN) or serum total bilirubin> 1.5×ULN.
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Severe or uncontrolled cardiovascular and cerebrovascular diseases requiring treatment, including:
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New York Heart Association class>2;
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Unstable angina pectoris that cannot be controlled by drugs;
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Myocardial infarction occurred within 6 months before the first administration of the study drug;
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Poorly controlled arrhythmias;
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12-lead ECG QTcF>470msec;
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Left ventricular ejection fraction <40%;
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Poorly controlled hypertension ;
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Stroke, cerebrovascular accident, or transient ischemic attack occurred within 6 months before the first administration of the study drug.
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Meets any of the following criteria:
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Known chronic obstructive pulmonary disease (COPD) and forced expiratory volume in 1 second (FEV1) <50% of predicted normal;
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Known moderate or severe persistent asthma, or a history of asthma within the past 2 years, or current uncontrolled asthma of any classification;
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with interstitial lung disease requiring corticosteroid therapy, drug-induced interstitial lung disease, a history of radiation pneumonitis, orclinically active interstitial lung disease suggested by any current evidence before the first administration of the study drug.
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Has an active bacterial, viral, or fungal infection or needs for intravenous antibiotic administration (IV) within 72 hours before the first administration of the study drug.
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Active or uncontrolled HBV , HCV , HIV positive.
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Is currently pregnant or breast feeding.
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Has any active severe mental illness, medical illness, or other symptoms/conditions that may affect treatment, compliance, or the ability to provide informed consent, as determined by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Chao-Yang Hospital，Capital Medicine University | Beijing | Beijing | China | 100000 |
| 2 | Peking university Third hospital | Beijing | Beijing | China | 100191 |
| 3 | The first affiliated hospital ,Sun Yat-sen University | Guangzhou | Guangdong | China | 510080 |
| 4 | The First Affiliated Hospital Zhejiang University School of Medicine | Hangzhou | Zhejiang | China |
Sponsors and Collaborators
- Zhejiang ACEA Pharmaceutical Co. Ltd.
Investigators
- Principal Investigator: jie jin, doctor, Zhejiang University
- Principal Investigator: juan li, doctor, First Affiliated Hospital, Sun Yat-Sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 38ADC-RRMM-C101