Clinical trial NCT05216965: A Clinical Study of 9MW2821 in Subjects With Advanced Malignant Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Lead sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-02-01
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 28 days post last drug administration
measure: Objective Response Rate (Phase 2)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE)
timeFrame: 24 months
measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE)
timeFrame: 24 months
measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE)
timeFrame: 24 months
measure: Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE)
timeFrame: 24 months
measure: Disease Control Rate
timeFrame: Up to 24 months
measure: Duration of Response
timeFrame: Up to 24 months
measure: Time to Response
timeFrame: Up to 24 months
measure: Progression Free Survival
timeFrame: Up to 24 months
measure: Overall Survival
timeFrame: Up to 24 months
measure: Incidence of Anti-Drug Antibody (ADA)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: