Safety and Efficacy Study of An Anti-CD38 Antibody Drug Conjugate in Relapsed or Refractory Multiple Myeloma

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.

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.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥18 years old, regardless of gender.
2. Previously treated with at least three drugs (including PI, IMiD, and anti-CD38 antibody), and relapsed/refractory after the most recent anti-MM therapy.
3. Diagnosis of MM according to IMWG criteria with measurable lesions, meeting at least 1 of the following criteria:

   * Serum M protein ≥ 0.5g/dL (≥ 5 g/L); or
   * Urine M protein ≥ 200mg/24 hours; or
   * 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).
4. ECOG performance status score is 0, 1, or 2.
5. Willing and able to comply with the study schedule and all other study protocol requirements.
6. 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:

1. Known hypersensitivity to any of the ingredients of this product.
2. Diagnosis of active plasma cell leukemia.
3. Diagnosis of systemic light chain amyloidosis.
4. MM involving the central nervous system.
5. Has POEMS syndrome.
6. There is spinal cord compression associated with MM.
7. Needs to take concomitant drugs with a strong inhibitory effect or a strong induction effect on CYP3A4.
8. Had received plasma exchange therapy within 28 days before the first administration of the study drug.
9. 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.
10. 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.
11. Had received autologous hematopoietic stem cell transplantation within 12 weeks before the first administration of the study drug.
12. Had undergone major surgery or eye surgery within 28 days before the first administration of the study drug.
13. Other malignant diseases within 3 years before the first administration of the study drug.
14. 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.
15. Has ≥ Grade 3 neuropathy or Grade 2 neuropathy with associated pain.
16. The toxicity caused by the previous anti-tumor treatment did not subside to ≤ grade 1.
17. Has the following hematological test results within 7 days before the first administration of the study drug:

    1. Hemoglobin \<80g/L
    2. Platelet count \<50×10\^9/L
    3. Absolute neutrophil count \<1.0×10\^9/L
18. Has the following blood chemistry test results within 7 days before the first administration of the study drug:

    1. Estimated creatinine clearance \<30mL/min.
    2. AST or ALT\>3×upper limit of normal (ULN) or serum total bilirubin\> 1.5×ULN.
19. Severe or uncontrolled cardiovascular and cerebrovascular diseases requiring treatment, including:

    1. New York Heart Association class\>2;
    2. Unstable angina pectoris that cannot be controlled by drugs;
    3. Myocardial infarction occurred within 6 months before the first administration of the study drug;
    4. Poorly controlled arrhythmias;
    5. 12-lead ECG QTcF\>470msec;
    6. Left ventricular ejection fraction \<40%;
    7. Poorly controlled hypertension ;
    8. Stroke, cerebrovascular accident, or transient ischemic attack occurred within 6 months before the first administration of the study drug.
20. Meets any of the following criteria:

    1. Known chronic obstructive pulmonary disease (COPD) and forced expiratory volume in 1 second (FEV1) \<50% of predicted normal;
    2. Known moderate or severe persistent asthma, or a history of asthma within the past 2 years, or current uncontrolled asthma of any classification;
    3. 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.
21. 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.
22. Active or uncontrolled HBV , HCV , HIV positive.
23. Is currently pregnant or breast feeding.
24. 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.