A Clinical Study of JMT101 in Combination With Osimertinib Versus Osimertinib Alone as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Sensitive Mutations

A Phase 3 Clinical Study of JMT101 in Combination With Osimertinib Versus Osimertinib Alone as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Sensitive Mutations

This is a Phase 3, randomized, positive-controlled, open-label clinical study. The primary objective is to evaluate the efficacy of JMT101 in combination with osimertinib versus osimertinib alone in patients with newly diagnosed locally advanced or metastatic non-squamous NSCLC harboring EGFR-sensitive mutations.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic Non-squamous NSCLC; Harboring EGFR Sensitive Mutations NSCLC; Previously Untreated Systematically NSCLC
• Intervention / Treatment: Drug: JMT101; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Estimated): 516
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat sen University Cancer Prevention and Treatment Center
    • Contact: Li Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be able to understand and voluntarily sign the written informed consent form (ICF);
2. Age ≥ 18 years old, male or female;
3. Participants with histologically or cytologically (pathology report required) confirmed non-squamous NSCLC that is unresectable and locally advanced or metastatic (stage IIIB, IIIC, or IV) according to the International Association for the Study of Lung Cancer (IASLC) 8th edition TNM staging criteria.
4. Participants who have no prior systemic anti-tumor therapy (including anti-EGFR targeted therapy, chemotherapy, biotherapy, immunotherapy, or any investigational drug) for locally advanced or metastatic NSCLC and are not amenable to radical surgery or radiotherapy. For participants with recurrent disease after prior surgical treatment who have undergone prior adjuvant and neoadjuvant therapy, it is necessary to confirm that there is no recurrence or metastasis of tumor within 6 months after surgery, and the randomization is > 6 months from the end of adjuvant/neoadjuvant therapy;
5. Have at least one measurable lesion that meets the RECIST 1.1 criteria at baseline. Target lesions must be either radiation naive or, if previously irradiated, there must be evidence of unequivocal disease progression after radiotherapy. Brain metastases should not be considered as target lesions;
6. ECOG PS score of 0 or 1;
7. Expected survival ≥ 3 months;
8. Have major organ and bone marrow functions that meet the following criteria within 7 days prior to the first dose in a non-intervention state:

1) Hematology:

1. Absolute neutrophil count (ANC) ≥ 1.5×109/L (prior to the hematology assessment, there is no treatment with cell growth factors within 7 days, and no treatment with long-acting granulocyte colony-stimulating factor (G-CSF) or pegylated recombinant human granulocyte colony-stimulating factor (PEG-CSF) within 14 days);
2. Platelets ≥ 90×109/L (there is no platelet transfusion or recombinant human thrombopoietin therapy within 7 days prior to hematology assessment);
3. Hemoglobin ≥ 90 g/L (there is no red blood cell transfusion/blood transfusion treatment within 14 days prior to hematology assessment); 2) Renal function: Serum creatinine ≤ 1.5×upper limit of normal (ULN), or creatinine clearance (CrCL) ≥ 50 mL/min (using the Cockcroft-Gault formula); 3) Liver function:

a. Total bilirubin ≤ 1.5×ULN (or ≤ 3×ULN for participants with Gilbert syndrome or metastases to liver); b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN (or AST and ALT ≤ 5×ULN for participants with metastases to liver); 4) Coagulation function:

1. International normalized ratio (INR) ≤ 1.5;
2. Activated partial thromboplastin time (APTT) ≤ 1.5×ULN;

Exclusion Criteria:

1. Participants with concomitant mutations such as ALK, ROS1, KRAS, BRAF, RET, MET, NTRK, and HER2, for which targeted drugs are commercially available for clinical treatment, who will not benefit from this clinical study as judged by the investigator; or participants with other mutations who will not benefit from this clinical study as judged by the investigator;
2. Have received Chinese patent medicine preparations for the treatment of lung cancer as an indication within 2 weeks prior to randomization;
3. Have received local radiotherapy within 2 weeks prior to randomization; have received more than 30% of bone marrow irradiation or extensive radiotherapy within 4 weeks prior to randomization;
4. Presence of pericardial effusion (small amount of pericardial effusion stable for ≥ 2 weeks prior to randomization is allowed);
5. Major surgery or severe traumatic injury within 4 weeks prior to the first study treatment, or anticipation of major surgery during the study. Some clinical procedures such as vascular access placement and aspiration biopsy are allowed;
6. Participants with meningeal metastases; spinal cord compression; symptomatic and unstable brain metastases, unless the participants have completed curative treatment, are in stable condition for at least 2 weeks prior to randomization and do not require steroid therapy. Participants with asymptomatic brain metastases may be enrolled if the investigator assesses that there is no indication for immediate curative treatment;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JMT101; JMT101 6mg/kg,intravenous drip,once every two weeks (Q2W), and osimertinib 80mg,orally,once daily(QD),with every 4weeks as a treatment cycle	Drug: JMT101; JMT101 is a recombinant humanized anti-EGFR monoclonal antibody.; Other Names: Recombinant Humanized Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Injection
Experimental: Osimertinib; Osimertinib 80 mg, orally, QD, with every 4 weeks as a treatment cycle.	Drug: Osimertinib; EGFR TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PFS assessed by the independent review committee (IRC) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Up to approximately 44 months after the first participant is enrolled

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to approximately 44 months after the first participant is enrolled
Objective response rate (ORR) assessed by IRC based on RECIST 1.1	Up to approximately 44 months after the first participant is enrolled
duration of response (DOR) assessed by IRC based on RECIST 1.1	Up to approximately 44 months after the first participant is enrolled
disease control rate (DCR) assessed by IRC based on RECIST 1.1	Up to approximately 44 months after the first participant is enrolled
DOR assessed by the investigator based on RECIST 1.1	Up to approximately 44 months after the first participant is enrolled
ORR assessed by the investigator based on RECIST 1.1	Up to approximately 44 months after the first participant is enrolled
DCR assessed by the investigator based on RECIST 1.1	Up to approximately 44 months after the first participant is enrolled
Adverse events incidence and severity	Up to approximately 44 months after the first participant is enrolled
Serum concentration of JMT101	Up to approximately 44 months after the first participant is enrolled
Incidence and titer of anti-drug antibodies (ADAs)	Up to approximately 44 months after the first participant is enrolled
The incidence of neutralising antibodies (NAbs)	Up to approximately 44 months after the first participant is enrolled

Collaborators and Investigators

• Sponsor: Shanghai JMT-Bio Inc.
• Investigators: Principal Investigator: Li Zhang, Sun Yat sen University Cancer Prevention and Treatment Center

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): May 30, 2029

Study Registration Dates

• First Submitted: December 7, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Hypersensitivity; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: JMT101-018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No