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: 116
• 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

NSCLC Stage IV; Malignant Pleural Effusions

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

• Puncture-free survival (PuFS)

  The time from removing the thoracic drainage tube after last intrapleural infusion to the time when re-drainage is required (based on the time when puncture and drainage occur) or death, whichever occurs first.

  The time from removing the thoracic drainage tube after last intrapleural infusion to the time when re-drainage is required or death, assessed up to 12 months after enrollment or randomization.

Secondary Outcomes (15)

• 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)

• Progression-free disease survival (PFS)

  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:

• Aged \>18 years and ≤ 75 years, male or female.
• Histologically or cytologically confirmed advanced non-small cell lung cancer that has progressed after at least one line of systemic anti-tumor treatment (including subjects with local malignant pleural effusion progression or inadequately controlled).
• Malignant pleural effusion requiring intrathoracic perfusion treatment (malignant pleural effusion should be diagnosed histologically or cytologically), with moderate or above amount of pleural effusion (the depth of pleural effusion by B-mode ultrasound in sitting position is ≥ 4 cm, and the actual drainage volume of pleural effusion is ≥ 500 mL), and the study physician judges that clinical intervention is required.
• If the subject received latest systemic treatment regimen at least 1 course (at least 21 days for targeted therapy) and poorly controlled pleural effusion , then no washout interval is required.
• Any toxicity from prior antineoplastic therapy should have recovered to Grade 0-1 as determined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) V5.0, except alopecia, pigmentation, and Grade ≤ 2 neuropathy, hypothyroidism on hormone replacement therapy, or other adverse events that are confirmed to be chronic.
• ECOG score (PS) of 0-1 (for subjects with inadequately controlled malignant pleural effusion of whom ECOG score is 2 can be enrolled).
• An expected survival ≥ 12 weeks. 8.8.Organ functions must meet the following criteria: Hemogram (no transfusion of blood or blood products, no correction with granulocyte-colony stimulating factor (G-CSF) or other hematopoietic stimulating factors within 14 days before the first dose): absolute neutrophil count (ANC) ≥ 1.5 109/L, platelet (PLT) ≥ 100 109/L, and hemoglobin (HGB) ≥ 85 g/L; Hepatic function: total bilirubin (TBIL) ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (AST and ALT ≤ 5 × ULN in case of liver metastasis), serum albumin \> 28 g/L; Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN.
• Understand and voluntarily sign the written informed consent form.

You may not qualify if:

• Subjects with recurrent pleural effusion within 4 weeks after the last intrathoracic perfusion treatment and requiring clinical intervention.
• Subjects who have received intrathoracic infusion of immune drugs, such as PD-1, PD-L1, CTLA-4, and other immune checkpoint inhibitors (excluding interleukins).
• Subjects with malignant pleural effusion requiring clinical intervention on both sides, or those in whom adequate drainage of pleural effusion is not possible due to objective reasons (including loculated pleural effusion), or complicated with chylothorax, or with moderate or greater pericardial effusion, or pneumothorax.
• Subjects with central nervous system (CNS) metastases resulting in clinical symptoms or requiring therapeutic intervention; patients with previously treated brain metastases can be enrolled if they are asymptomatic and have stable disease as indicated by imaging examination ≥ 4 weeks before the first dose and do not require corticosteroids or anticonvulsant therapy.
• Subjects with known history of severe allergy to any ingredient of M701 or similar macromolecular antibody drugs.
• Subjects with contraindications to thoracentesis.
• Subjects who have undergone major surgery within 4 weeks before the first dose.
• Subjects combined with active infection that have not been controlled to a clinically stable state within the previous 3 days before randomization.
• Subjects who require long-term hormone or immunosuppressive therapy, such as active autoimmune diseases, maintenance therapy after organ transplantation, but patients with the following conditions are allowed to be screened: type I diabetes; hypothyroidism that can be controlled by replacement therapy only; skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
• Subjects with severe respiratory diseases or interstitial pneumonia, who are not suitable for enrollment as determined by the investigator.
• Combined with severe cardiovascular disease, including cardiac insufficiency (New York Heart Association class III-IV), or acute cardiovascular event (such as acute myocardial infarction, acute cerebral infarction, angina pectoris unstable, hemorrhage brain, etc.) or pulmonary embolism within the past 6 months, or received a vascular stent implantation (such as coronary artery stent implantation, intracranial artery stent implantation, etc.) within the past 6 months; or experienced a new venous thrombotic disease such as lower extremity venous thrombosis has occurred within the past 1 month.
• The mean corrected QT interval (QTcF) \> 450 ms (male) or \> 470 ms (female) in 3 electrocardiogram (ECG) examinations at screening (only those with QTcF \> 450 ms (male) or \> 470 ms (female) at the first ECG examination should be retested to obtain the mean corrected value of 3 retests); family or personal history of long or short QT syndrome; clinically significant history of arrhythmia, or implantation of defibrillation device for ventricular arrhythmia.
• History of malignancy (other than the study tumor) within 3 years prior to the date of first dose of investigational drug (except for squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other non-invasive diseases that are considered by the investigator and the sponsor to be cured with minimal risk of recurrence within 3 years).
• Combined with active chronic hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\]-positive and/or hepatitis B core antibody (HBcAb)-positive, with HBV-DNA quantification ≥1×10⁴ copies/mL or ≥2000 IU/mL), active hepatitis C (hepatitis C antibody-positive, and \[e.g., hepatitis C virus (HCV-RNA) higher than the analytical method\] antibody-positive, with HCV-RNA ≥ the lower limit of detection), \[,\] human immunodeficiency virus (HIV) antibody-positive or active syphilis, HIV antibody-positive infection (syphilis-specific antibody-positive and syphilis non-specific antibody-positive);
• Pregnant or lactating women; men or women who plan to have children within 6 months after the end of this clinical study.

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 (Estimated): September 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)