A Study to Evaluate 9MW2821 Versus Treatment of Physician's Choice for Subjects With Recurrent or Metastatic Cervical Cancer

A Randomized, Open-label, Phase 3 Study to Evaluate 9MW2821 vs Treatment of Physician's Choice in Subjects With Recurrent or Metastatic Cervical Cancer Who Progressed on or After Platinum-based Chemotherapy

The purpose of this study is to compare the efficacy and safety of 9MW2821 and chemotherapy in participants with recurrent or metastatic cervical cancer who progressed on or after platinum-based chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: 9MW2821; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lingying Wu, Professor; Phone Number: +8601067781331; Email: wulingying@csco.org.cn
• Study Contact Backup: Name: Huijuan Yang, Professor; Phone Number: +8602164175590; Email: huijuanyang@hotmail.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Hospital Chinese Academy of Medical Sciences
    • Contact: Lingying Wu, Professor; Phone Number: +8601067781331; Email: wulingying@csco.org.cn
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Huijuan Yang, Professor; Phone Number: +8602164175590; Email: huijuanyang@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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. Female subjects aged 18 to 75 years (including 18 and 75 years).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Histologically confirmed recurrent or metastatic cervical cancer (squamous cell, HPV-associated adenocarcinoma, or adenosquamous), not amenable to resection or chemoradiation with curative intent.
5. Subject must have received a platinum-based chemotherapy with or without bevacizumab and received no more than 2 prior systemic therapy in the metastatic/recurrent setting. Subject must have experienced radiographic progression during or after the last treatment regimen.
6. An archival tumor tissue sample or a fresh tissue sample should be provided.
7. Life expectancy of ≥ 12 weeks.
8. Subjects must have measurable disease according to RECIST (version 1.1).
9. Adequate to receive one of the chemotherapy regimens in the control group (gemcitabine, pemetrexed, topotecan);
10. Adequate organ functions.
11. Sexually active fertile subjects must agree to use methods of contraception during the study and at least 6 months after termination of study therapy.
12. Subjects are willing to follow study procedures.

Exclusion Criteria:

1. Has other histologies not mentioned as part of the inclusion criteria above, i.e. HPV-independent adenocarcinoma or primary neuroendocrine.
2. Chemotherapy or radiotherapy within 21 days prior to the first dose of study drug, traditional Chinese medicine with anticancer indication within 14 days prior to the first dose of study drug, use of any investigational drug or device within 28 days prior to the first dose of study drug, received treatment of nectin-4 targeted ADC, received treatment of ADC with MMAE payload, received any strong CYP3A4 inhibitors within 14 days prior to the first dose of study drug.
3. Preexisting treatment related toxicity Grade ≥ 2. Subjects experienced Grade ≥ 3 immune related adverse events during or after immunotherapy.
4. Subjects had clinically significant hydronephrosis that could not be relieved by nephrostomy or urethral stenting, as determined by the investigator.
5. Major surgery within 28 days prior to first dose of study drug.
6. Hemoglobin A1C (HbA1c) ≥ 8%.
7. Preexisting peripheral neuropathy Grade ≥ 2.
8. Any live vaccines within 28 days before first dose of study drug or during the study.
9. Documented history of clinically significant cardiac or cerebrovascular diseases within 6 months prior to the first dose of study drug.
10. Other severe or uncontrolled disease, i.e. severe respiratory system disease, thromboembolic events, active bleeding or active infection.
11. Central nervous system metastases.
12. History of another malignancy within 3 years before the first dose of study drug. Subjects with cured malignancies are allowed.
13. History of autoimmune disease requiring systemic treatment within 2 years before the first dose of study drug.
14. Has ocular conditions that may increase the risk of corneal epithelium damage.
15. Known sensitivity to any of the ingredients of the investigational product; History of drug abuse or mental illness.
16. Uncontrolled tumor-related bone pain or spinal cord compression.
17. Pleural effusion, ascites or pericardial effusion with syptoms or needed drainage.
18. Condition or situation which may put the subject at significant risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 9MW2821	Drug: 9MW2821; 1.25mg/kg of 9MW2821 by intravenous infusion on days 1, 8 and 15 of every 28-day cycle
Active Comparator: Treatment of Physician's Choice	Drug: Chemotherapy; 1.0 or 1.25 mg/m ^2 topotecan by intravenous infusion on days 1 to 5 or 1000 mg/m ^2 gemcitabine by intravenous infusion on days 1 and 8 or 500 mg/m ^2 pemetrexed by intravenous infusion on day 1 of every 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from the date of randomization until the date of death from any cause.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events		Up to 3 years
Incidence of Anti-Drug Antibody (ADA)		Up to 3 years
Objective Response Rate per investigator	The percentage of subjects who experience a best response of either CR or PR.	Up to 3 years
Disease Control Rate per investigator	The percentage of subjects who experience a best response of CR, PR or stable disease (SD).	Up to 3 years
Progression Free Survival per investigator	Time from the date of first randomization to the earliest date of documented disease progression per radiological evidence or death from any cause.	Up to 3 years
Duration of Response per investigator	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.	Up to 3 years
Time to response per investigator	Time from the date of randomization to the date of CR or PR.	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality-of-life questionnaire (QLQ-C30）	The EORTC QLQ-C30 is a 30-question instrument designed to assess overall QoL in cancer patients with 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptomatic scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items were scored from 1 ("not at all") to 4 ("very much"), with the exception of items contributing to the GHS/QoL, which were scored from 1 ("very poor") to 7 ("excellent"). Raw scores were linearly transformed so that all transformed scores ranged from 0 to 100. For the overall health status/quality of life scale and the 5 functioning scales, high scores indicated better overall health status/functioning, and negative change from baseline indicated less improvement. For the symptom scales, a high score indicates a high level of symptomatology, while a negative change from baseline indicates improvement in symptoms.	Up to 3 years
EORTC Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24) Total Scores	The EORTC QLQ-CX24 questionnaire is intended for patients with cervical cancer with different disease stages and treatment modalities. The EORTC-QLQ-CX24 questionnaire consists of 24 questions with answers ranging from 1 (not at all) to 4 (very much). Four functional scales and five symptom scales will be calculated using the EORTC QLQ-CX24 Scoring Manual. The 9 scores calculated from the EORTC-QLQ-CX24 questionnaire will be summarized in descriptive statistics by treatment arm. A high score indicates a high level of symptomatology, while a negative change from baseline indicates improvement in symptoms.	Up to 3 years

Collaborators and Investigators

• Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2024
• Primary Completion (Estimated): December 9, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Neoplasms; Genital Neoplasms, Female; Uterine Neoplasms; Uterine Diseases; Uterine Cervical Diseases
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: 9MW2821-CP304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No