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

Relapsed or Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05565807
• Other study ID #: 38ADC-RRMM-C101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 9, 2023
• Est. completion date: February 19, 2027

Study information

• Verified date: August 2023
• Source: Zhejiang ACEA Pharmaceutical Co. Ltd.
• Contact: chao wang, master
• Phone: 15838131673
• Email: chao.wang[@]aceapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: February 19, 2027
• Est. primary completion date: March 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Biological:
• STI-6129
Anti-CD38 A2 human antibody drug conjugate (ADC) containing an antibody covalently bound to a duostatin tubulin inhibitor.

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital,Capital Medicine University	Beijing	Beijing
China	Peking university Third hospital	Beijing	Beijing
China	The first affiliated hospital ,Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang ACEA Pharmaceutical Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events(AEs)	Assessing the incidence of adverse events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE Version 5).	Up to 2 years
Primary	Overall response rate(ORR)	ORR assessed by the modified IMWG response criteria.	Up to 2 years
Secondary	Plasma concentration of the total anti-CD38 antibody	Determine plasma levels of the total antibody.	Up to 2 years
Secondary	Plasma concentration of conjugated toxin	Determine plasma levels of conjugated toxin (STI 6129).	Up to 2 years
Secondary	Plasma concentration of the free toxin	Determine plasma levels of the free toxin (duostatin 5.2).	Up to 2 years
Secondary	Recommended Phase 2 dose (RP2D)	Determined according to the phase 1b.	Up to 2 years
Secondary	Progression-Free Survival	PFS is the period from patient enrollment until PD or death.	Up to 2 years
Secondary	Overall Survival (OS)	OS is the period from enrollment until death from any cause.	Up to 2 years
Secondary	Time To First Response(TTR)	TTR is the period from the date of patient registration to the date of first response.	Up to 2 years
Secondary	Duration of Response (DOR)	DOR is the period from the first documentation of response (CR or PR) to the first documentation of PD.	Up to 2 years
Secondary	Clinical Benefit Rate (CBR)	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.	Up to 2 years