Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Pleural Effusion, Malignant

Pleural Effusion

Respiratory Tract Neoplasms

Thoracic Neoplasms

Respiratory Tract Diseases

Pleural Diseases

Pleural Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Cisplatin

Antibodies, Bispecific

Immunoglobulins

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

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

M701 pleural infusion

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

Pleural drainage

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

Cisplatin pleural infusion

ShaoYi Huang

Yong Xu

Yiping Zhang

Zhengbo Song

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.

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.

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

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

ORR is defined as percentage of participants who achieved complete response (CR), partial response (PR), based on RESIST 1.1 .

ORR is defined as percentage of participants who achieved complete response (CR), partial response (PR), and stable disease (SD), based on RESIST 1.1 .

Duration of disease control(DDC) was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, based on RESIST 1.1 .

PFS was defined as the time between the date of first dose of M701 and either disease progression or death, whichever occurs first.

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

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.

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

The endpoints for assessment of PK of M701 include serum concentrations of M701 at different timepoints after M701 administration.

The immunogenicity of M701 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

The immunogenicity of M701 will be collected by testing the antibody titer of the neutralizing antibody.

As tumor biomarkers, concentrations of CEA, CyFra21-1, SCC and NSE in malignant pleural effusions will be examined at Day 1 and Day10.

The number and expression levels of EpCAM-positive cells in pleural effusions will be measured by pathological methods (including cytospin, immunohistochemical techniques, etc.)

Ratio of EpCAM positive tumour cell/leucocyte in pleural effusions will be measured by FACS method.

the rate of patients with successful pleurodesis at 4 weeks / 8 weeks

the rate of patients without extra puncture at 4/8 weeks after the initial drainage.

Using the Lister Quadruple Scale to record pleural effusions at 4 weeks/ 8 weeks.

Spots Global Cancer Trial Database for pleural drainage