A Phase Ib/II Clinical Trial of M701 in the Treatment of Malignant Pleural Effusions Caused by NSCLC

NCT05543330 | Recruiting Phase 1

• 1 other identifier: M70103
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1/phase 2, multicenter, open-label study to evaluate the safety, tolerability, PK, PD, immunogenicity and preliminary efficacy of M701 in patients with treatment of malignant pleural effusions caused by NSCLC.

Conditions

Malignant Pleural Effusions; NSCLC Stage IV

Keywords

Malignant Pleural Effusions; NSCLC

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicities (DLTs)

  Dose limiting toxicities during the first 28 days after the first administrations of study drug in each cohort.

  From the time of the first dose (Day 1) until the forth dosing (Day 28)

• Incidence of AEs

  Incidence and severity of AEs, including but not limited to vital signs, physical examination, laboratory tests. All AEs will be classified as Grades 1 through 5 as defined by NCI CTCAE v5.0.

  From the start of administration to the end of the study or 28 days after the administration is stopped

• Objective Response Rate(4 weeks/8 weeks) of pleural effusion

  the rate of patients with pleural effusion CR and PR at 4 weeks / 8 weeks, based on CT evaluation .

  From the time of first dosing (Day 1) until disease progression(up to 56 days)

Secondary Outcomes (12)

• Area under the curve (AUC) of M701

  From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)

• Maximum observed concentration (Cmax) of M701

  From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)

• Minimum observed concentration (Cmin) of M701

  From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)

• Half-time (t1/2) of M701

  From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)

• Anti-drug antibodies(ADAs) titer

  From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)

Other Outcomes (5)

• Objective Response Rate of Tumor

  From the time of first dosing (Day 1) until disease progression (up to 56 days)

• Disease Control Rate of tumor

  From the time of first dosing (Day 1) until disease progression (up to 56 days)

• Duration of disease control(DDC)

  12 months (anticipated)

Study Arms (2)

Experimental group

EXPERIMENTAL

Pleural drainage and M701 infusion

Drug: M701 pleural infusion; Procedure: Pleural drainage

Control group

SHAM COMPARATOR

Pleural drainage only or plus chemotherapy as investigator's choice.

Procedure: Pleural drainage; Drug: Cisplatin pleural infusion

Interventions

M701 pleural infusion DRUG

M701 pleural infusion on Days 1,4,7 and 10.

Experimental group

Pleural drainage PROCEDURE

Pleural effusion drainage via Ultra-sound guidance on Day 1.

Control group; Experimental group

Cisplatin pleural infusion DRUG

Cisplatin pleural infusion (30-50mg/m2) on Day 1.

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, aged \> 18 years.
• Histologically- or cytologically-confirmed non-small cell lung cancer that has progressed after first line systemic therapy.
• Malignant pleural effusion diagnosed histologically or cytologically, with moderate or above moderate pleural fluid (sitting pleural fluid depth ≥ 4 cm via ultrasound, expected pleural fluid volume ≥ 500 mL) . Require clinical intervention and not treated yet.
• Patients who have an washout period of ≥ 4 weeks or 5 half-life of the drug (including radiotherapy, chemotherapy, immunotherapy, biologic, targeted, hormonal therapy, and 14 days for local radiotherapy) between the last systemic therapy and the first dose; however, no washout period is required if the subject has new pleural fluid or poor control of current pleural fluid after at least 2 cycle systemic therapy.
• Patients who had recovered to grade 0-1 of any toxic reaction to prior antineoplastic therapy as determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) V5.0, with the exception of alopecia, hyperpigmentation and ≤ grade 2 neuropathy, hormone replacement hypothyroidism or other adverse events confirmed to have turned chronic.
• Patients with physical status ECOG score (PS) of 0-2.
• Patients with life expectancy ≥ 12 weeks.
• Bone marrow: absolute neutrophil count (ANC) ≥ 1.5 ×10\^9/L, platelet count ≥ 100 ×10\^9/L, hemoglobin ≥ 8.5 g/dL (without blood transfusion within14 days of the first dose of study drug); Liver: bilirubin (TBIL)≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 3 x ULN ( ≤ 5 x ULN in case of liver metastases); Kidney: serum creatinine ≤1.5 x ULN.
• Patients must understand and voluntarily sign the written informed consent.

You may not qualify if:

• Patients with asymptomatic pleural fluid and not requiring clinical intervention, or bilateral malignant pleural fluid, or proposed perfusion of the chest cavity presenting with pleural fluid separation.
• Patients with central nervous system (CNS) metastases resulting in clinical symptoms or requiring therapeutic intervention; patients previously treated for brain metastases may be enrolled if they have been asymptomatic for ≥ 4 weeks prior to the first dose and have imaging indicating stable disease and do not require corticosteroid or anticonvulsant therapy.
• Patients with a known history of severe allergy to M701 drug components or antibody-like macromolecular drugs.
• Patients with contraindications to thoracentesis.
• Patients who have undergone major surgical procedures within 4 weeks prior to the first dose.
• Patients with extensive liver metastases (\>70%).
• Patients with uncontrollable active infection (NCI-CTCAE V5.0 ≥ grade 2).
• Patients required long-term hormonal or immunosuppressive therapy, e.g. active autoimmune disease, maintenance therapy after organ transplantation, except that the following are allowed to enter screening: type I diabetes mellitus, hypothyroidism that can be controlled by replacement therapy only, skin diseases that do not require systemic therapy (e.g. vitiligo, psoriasis or alopecia).
• Patients with severe respiratory disease which, in the judgment of the investigator, makes them unsuitable for entry; or combined interstitial pneumonia.
• Patients with history of severe cardiovascular disease, including previous coronary artery bypass grafting or coronary stenting, myocardial infarction within 6 months, congestive heart failure (New York Classification of Cardiac Function Class III-IV) or unstable angina, or uncontrolled hypertension.
• Patients with QTc interval \> 480 ms,family or personal history of long or short QT syndrome, clinically significant history of ventricular arrhythmias or implantation of a defibrillation device for ventricular arrhythmias.
• Patients with a history of (non-study tumour) malignancy (except squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other, non-invasive lesions that the investigator and sponsor agree have been cured and have a minimal risk of recurrence within 3 years) within 3 years prior to the date of first study drug administration.
• Patients who have active hepatitis B (HBV-DNA quantification ≥ 1 x 10\^4 copies/mL or 2000 IU/mL), active hepatitis C (positive for hepatitis C antibodies and HCV-RNA above the lower limit of detection of the assay), active syphilis with positive HIV antibodies.
• Pregnant or breastfeeding woman,Plan to conceive within six months;
• Patients with a confirmed history of neurological or mental disorders, including epilepsy and dementia.

Sponsors & Collaborators

• Wuhan YZY Biopharma Co., Ltd.: lead

Study Sites (1)

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Conditions

Pleural Effusion, Malignant; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Lung Diseases

Study Officials

• Yiping Zhang

  Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

  PRINCIPAL INVESTIGATOR

• Zhengbo Song

  Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ShaoYi Huang

CONTACT

86-027-82668440; huangshaoyi@yzybio.com

Li Huang

CONTACT

13647219857; huangli@yzybio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: For Phase 2 study, the patients are enrolled into 2 arm parallelly.

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 16, 2022
• Study Start: September 30, 2022
• Primary Completion: April 30, 2026
• Study Completion (Estimated): October 15, 2026
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)