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

Official title

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

Overview

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.

Interventions

• Drug 9MW2821
  1.25mg/kg of 9MW2821 by intravenous infusion on days 1, 8 and 15 of every 28-day cycle
• 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

Primary outcome measures

• Overall Survival [Time frame: Up to 3 years]

Secondary outcome measures (7)

• Objective Response Rate per investigator [Time frame: Up to 3 years]
• Disease Control Rate per investigator [Time frame: Up to 3 years]
• Progression Free Survival per investigator [Time frame: Up to 3 years]
• Duration of Response per investigator [Time frame: Up to 3 years]
• Time to response per investigator [Time frame: Up to 3 years]
• Incidence of adverse events [Time frame: Up to 3 years]
• Incidence of Anti-Drug Antibody (ADA) [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

• Competent to comprehend, sign, and date an independent ethics committee/institutional review board/research ethics board (IEC/IRB/REB) approved informed consent form.
• Female subjects aged 18 to 75 years (including 18 and 75 years).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed recurrent or metastatic cervical cancer (squamous cell, HPV-associated adenocarcinoma, or adenosquamous), not amenable to resection or chemoradiation with curative intent.
• 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.
• An archival tumor tissue sample or a fresh tissue sample should be provided.
• Life expectancy of ≥ 12 weeks.
• Subjects must have measurable disease according to RECIST (version 1.1).
• Adequate to receive one of the chemotherapy regimens in the control group (gemcitabine, pemetrexed, topotecan);
• Adequate organ functions.
• Sexually active fertile subjects must agree to use methods of contraception during the study and at least 6 months after termination of study therapy.
• Subjects are willing to follow study procedures.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Fudan University Shanghai Cancer Center — Shanghai

Publications

• Zhang J, Liu R, Wang S, Feng Z, Yang H, Gao S, Li X, Yao X, Chen J, Gong Z, Li Y, Li X, Wang S, Hu C, Liu J, Zhang M, Yuan F, Shi B, Lou H, Zhao P, Qiu F, Guo H, Hu B, Xu D, Huang H, Zhang X, Feng M, Wang X, Li G, Liu D, Chen X, Wang P. Bulumtatug Fuvedotin (BFv, 9MW2821), a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open-l PMID 40288679

Identifiers

NCT: NCT06692166 · 9MW2821-CP304

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗