A Clinical Study of 9MW2821 in Subjects With Advanced Malignant Solid Tumors

• ClinicalTrials.gov Identifier: NCT05216965
• Recruitment Status: Recruiting
• First Posted: February 1, 2022
• Last Update Posted: June 15, 2022
• Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.
• Information provided by (Responsible Party): Mabwell (Shanghai) Bioscience Co., Ltd.

Study Description

Brief Summary:

This study is a Phase 1/2, first-in-human, open-label, dose-escalation and cohort expansion study designed to characterize the safety, tolerability, pharmacokinetics, preliminary antitumor activity and immunogenicity of 9MW2821 administered by intravenous (IV) infusion.

Condition or disease	Intervention/treatment	Phase
Solid Tumors	Drug: 9MW2821	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 208 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Clinical Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of 9MW2821 in Subjects With Advanced Malignant Solid Tumors
• Actual Study Start Date: June 11, 2022
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: 9MW2821	Drug: 9MW2821; All subjects will receive a single intravenous (IV) infusion of 9MW2821 once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events [ Time Frame: Up to 28 days post last drug administration ]
2. Objective Response Rate (Phase 2) [ Time Frame: Up to 24 months ]
   Defined as the percentage of subjects who experience a best response of either CR or PR. CR and PR must be confirmed ≥ 28 days later.

Secondary Outcome Measures :

1. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) [ Time Frame: 24 months ]
   Maximum observed concentration (Cmax)
2. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) [ Time Frame: 24 months ]
   Area under the concentration-time curve (AUC)
3. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) [ Time Frame: 24 months ]
   Half-life (t1/2)
4. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) [ Time Frame: 24 months ]
   Clearance (CL)
5. Disease Control Rate [ Time Frame: Up to 24 months ]
   Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)
6. Duration of Response [ Time Frame: Up to 24 months ]
   Time from the date of the first complete response (CR) or partial response (PR) to the earliest date of disease progression or death from any cause. DOR is only defined for subjects who have best overall response of CR or PR.
7. Time to Response [ Time Frame: Up to 24 months ]
   Time from the date of first infusion to the date of confirmed CR or PR
8. Progression Free Survival [ Time Frame: Up to 24 months ]
   Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause
9. Overall Survival [ Time Frame: Up to 24 months ]
   Time from the date of first infusion until the date of death from any cause.
10. Incidence of Anti-Drug Antibody (ADA) [ Time Frame: Up to 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Competent to comprehend, sign, and date an independent ethics committee/institutional review board/research ethics board (IEC/IRB/REB) approved informed consent form.
2. Male or female subjects aged 18 to 80 years (including 18 and 80 years).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Histologically or cytologically confirmed advanced malignant solid tumors (except sarcoma).
5. For Cohort Expansion: Subjects must submit tumor tissue for Nectin-4 expression.
6. Life expectancy of ≥ 3 months.
7. Subjects must have measurable disease according to RECIST (version 1.1).
8. Adequate organ functions.
9. Sexually active fertile subjects, and their partners, must agree to use methods of contraception during the study and at least 6 months after termination of study therapy.
10. Subjects are willing to follow study procedures.

Exclusion Criteria:

1. Chemotherapy or radiotherapy within 21 days prior to the first dose of study drug, or any other anticancer therapy within 14 days prior to the first dose of study drug.
2. Preexisting treatment related toxicity Grade ≥ 2 (except alopecia).
3. Major surgery within 28 days prior to first dose of study drug.
4. History of uncontrolled diabetes mellitus.
5. Preexisting peripheral neuropathy Grade ≥ 2.
6. Received treatment of nectin-4 targeted ADC with MMAE payload.
7. Any live vaccines within 4 weeks before first dose of study drug or during the study.
8. Documented history of clinically significant cardiac or cerebrovascular diseases within 6 months prior to the first dose of study drug.
9. Other severe or uncontrolled disease, i.e. severe respiratory system disease, thromboembolic events, active bleeding or active infection.
10. Uncontrolled central nervous system metastases.
11. History of another malignancy within 3 years before the first dose of study drug. Subjects with curable malignancies are allowed.
12. History of autoimmune disease requiring systemic treatment within 2 years before the first dose of study drug.
13. Has ocular conditions that may increase the risk of corneal epithelium damage.
14. Known sensitivity to any of the ingredients of the investigational product; History of drug abuse or mental illness.
15. Any P-glycoprotein (P-gp) inducers/inhibitors or CYP3A4 inducers/inhibitors within 14 days prior to the first dose of study drug
16. Use of any investigational drug or device within 2 months prior to the first dose of study drug.
17. Condition or situation which may put the subject at significant risk.

Contacts and Locations

Locations

China, Shanghai

Fudan University Shanghai Cancer Center; Recruiting

Shanghai, Shanghai, China, 200032

Contact: Jian Zhang, Professor 13918273761 syner2000@163.com

Principal Investigator: Jian Zhang, Professor

Sponsors and Collaborators

Mabwell (Shanghai) Bioscience Co., Ltd.

More Information

• Responsible Party: Mabwell (Shanghai) Bioscience Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05216965
• Other Study ID Numbers: 9MW2821-2021-CP102
• First Posted: February 1, 2022
• Last Update Posted: June 15, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms