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

A Phase 1, Multicenter, Open-label, Dose-increasing Study to Evaluate the Safety, Tolerability, PK/PD and Preliminary Efficacy of M701, a Recombinant Epcam and CD3 Bispecific Antibody , in Patients With Malignant Pleural Effusions Caused by NSCLC

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.

Study Overview

• Status: Recruiting
• Conditions: NSCLC Stage IV; Malignant Pleural Effusions
• Intervention / Treatment: Drug: M701 pleural infusion; Procedure: Pleural drainage; Drug: Cisplatin pleural infusion

Detailed Description

This study is consisted of two phase, Phase Ib and II:

Phase 1b includes dose escalation phase and cohort expansion phase. In dose escalation phase, up to 4 dose-escalation cohorts will be sequentially enrolled with regular "3+3" design. DLTs will be evaluated during the first treatment cycle, which is 28 days. In cohort expansion phase, after the RP2D was identified, participants were enrolled in an open-ended manner. Participants were assigned to groups A(3 injections), B (4 injections)and C(6 injections) on a 1:1:1 basis to evaluate the dose frequency.

Phase II:The dose and dosing frequency of M701 drug for the Phase II clinical trial were determined based on a combination of the tolerance1 and efficacy of M701 in the Phase Ib trial. Then the participants were randomly divided into two groups: the test group(M701) and the control group(cisplatin or pleural effusions suctions). The pleural effusions response (ORR) and Puncture Free Survival （PuFS）will be evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ShaoYi Huang; Phone Number: 86-027-82668440; Email: huangshaoyi@yzybio.com
• Study Contact Backup: Name: Li Huang; Phone Number: 13647219857; Email: huangli@yzybio.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
      • Principal Investigator: Yiping Zhang
      • Principal Investigator: Zhengbo Song
      • Contact: Weizhen Xu; Phone Number: zjchgcp@163.com; Email: zjchgcp@163.com
      • Contact: Zhengbo Song; Phone Number: 0571-88122168; Email: songzb@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged >18 years and ≤ 75 years, male or female.
2. 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).
3. 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.
4. 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.
5. 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.
6. ECOG score (PS) of 0-1 (for subjects with inadequately controlled malignant pleural effusion of whom ECOG score is 2 can be enrolled).
7. 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.

9.Understand and voluntarily sign the written informed consent form.

Exclusion Criteria:

1. Subjects with recurrent pleural effusion within 4 weeks after the last intrathoracic perfusion treatment and requiring clinical intervention.
2. Subjects who have received intrathoracic infusion of immune drugs, such as PD-1, PD-L1, CTLA-4, and other immune checkpoint inhibitors (excluding interleukins).
3. 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.
4. 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.
5. Subjects with known history of severe allergy to any ingredient of M701 or similar macromolecular antibody drugs.
6. Subjects with contraindications to thoracentesis.
7. Subjects who have undergone major surgery within 4 weeks before the first dose.
8. Subjects combined with active infection that have not been controlled to a clinically stable state within the previous 3 days before randomization.
9. 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).
10. Subjects with severe respiratory diseases or interstitial pneumonia, who are not suitable for enrollment as determined by the investigator.
11. 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.
12. 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.
13. 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).
14. 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);
15. Pregnant or lactating women; men or women who plan to have children within 6 months after the end of this clinical study.
16. Subjects with a history of confirmed neurological or mental disorders who cannot cooperate with the treatment and follow the doctor's advice as judged by the investigator.
17. Other conditions that the investigator considers unsuitable for participating in this clinical study.

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: Experimental group; Pleural drainage and M701 infusion	Drug: M701 pleural infusion; M701 pleural infusion on Days 1,4,7 and 10.; Procedure: Pleural drainage; Pleural effusion drainage via Ultra-sound guidance on Day 1.
Sham Comparator: Control group; Pleural drainage only or plus chemotherapy as investigator's choice.	Procedure: Pleural drainage; Pleural effusion drainage via Ultra-sound guidance on Day 1.; Drug: Cisplatin pleural infusion; Cisplatin pleural infusion (30-50mg/m2) on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of M701	The endpoints for assessment of PK of M701 include serum concentrations of M701 at different timepoints after M701 administration.	From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)
Maximum observed concentration (Cmax) of M701	The endpoints for assessment of PK of M701 include serum concentrations of M701 at different timepoints after M701 administration.	From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)
Minimum observed concentration (Cmin) of M701	The endpoints for assessment of PK of M701 include serum concentrations of M701 at different timepoints after M701 administration.	From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)
Half-time (t1/2) of M701	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	The immunogenicity of M701 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).	From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)
Neutralizing antibody titer	The immunogenicity of M701 will be collected by testing the antibody titer of the neutralizing antibody.	From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 16 days)
Concentrations of tumor biomarker in pleural effusions	As tumor biomarkers, concentrations of CEA, CyFra21-1, SCC and NSE in malignant pleural effusions will be examined at Day 1 and Day10.	From the time of first dosing (Day 1) until disease progression or toxicity intolerance(up to 56 days)
Expression level of EpCAM-positive cells in pleural effusions	The number and expression levels of EpCAM-positive cells in pleural effusions will be measured by pathological methods (including cytospin, immunohistochemical techniques, etc.)	From the time of first dosing (Day 1) until disease progression (up to 56 days)
Ratio of EpCAM-positive tumour cell/leucocyte	Ratio of EpCAM positive tumour cell/leucocyte in pleural effusions will be measured by FACS method.	From the time of first dosing (Day 1) until disease progression (up to 56 days)
Rate of with successful pleurodesis (4/8 weeks)	the rate of patients with successful pleurodesis at 4 weeks / 8 weeks	From the time of first dosing (Day 1) until disease progression (up to 56 days)
Pleural signs and symptoms	Using the Lister Quadruple Scale to record pleural effusions at 4 weeks/ 8 weeks.	From the time of first dosing (Day 1) until disease progression (up to 56 days)
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.
Puncture-free survival rate at 8 and 14 weeks after the first intrapleural dose.	Puncture-free survival rate at 8 and 14 weeks after the first intrapleural dose.	8 weeks and 14 weeks following the first dose .
Time to Next Puncture (TTNP)	Defined to be the period from the end of the treatment (based on the time when the thoracic drainage tube is removed, the same as the starting time point of PuFS) to the time when the subject requires another thoracic puncture for drainage.	The time from removing the thoracic drainage tube after last intrapleural infusion to the time when re-drainage is required, assessed up to 12 months after enrollment or randomization.
Quality of life score	Evaluated according to the EORTC quality of life scale QLQ-C30 (V3.0) and scale QLQ-LC13 (see Appendix 3 for details)	From Day 1 (enrollment or randomization) to the end of the study , up to 1 year.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate of Tumor	ORR is defined as percentage of participants who achieved complete response (CR), partial response (PR), based on RESIST 1.1 .	From the time of first dosing (Day 1) until disease progression (up to 56 days)
Disease Control Rate of tumor	ORR is defined as percentage of participants who achieved complete response (CR), partial response (PR), and stable disease (SD), based on RESIST 1.1 .	From the time of first dosing (Day 1) until disease progression (up to 56 days)
Progression-free disease survival (PFS)	PFS was defined as the time between the date of first dose of M701 and either disease progression or death, whichever occurs first.	12 months (anticipated)
Half-year / One-year Survival Rates	Half-year / One-year Survival Rates	1 year (anticipated)
Overall Survival (OS)	The time from the start of randomization to death due to any cause.	From the first dose until death

Collaborators and Investigators

• Sponsor: Wuhan YZY Biopharma Co., Ltd.
• Investigators: Principal Investigator: 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)

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Malignant Pleural Effusions
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Pleural Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pleural Diseases; Pleural Effusion; Carcinoma, Non-Small-Cell Lung; Pleural Effusion, Malignant; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: M70103

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
• product manufactured in and exported from the U.S.: No