JMT101 in Combination With Osimertinib, Versus Cisplatin-pemetrexed in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Characterized by Epithermal Growth Factor Receptor (EGFR) Exon 20ins Mutations

A Randomized, Open-label, Parallel-controlled Phase 3 Study of Combination JMT101 and Osimertinib Compared With Cisplatin -Pemetrexed in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This is a multicenter, randomized, open-label, parallel-controlled phase 3 study. This study aims to evaluate the efficacy and safety of JMT101 combined with Osimertinib compared with Cisplatin combined with pemetrexed in participants with local advanced or metastatic non-small-cell lung cancer harboured EGFR 20ins mutation without prior systemic therapy.

Primary objective of this study is to assess the efficacy of JMT101 combined with Osimertinib versus Cisplatin combined with pemetrexed using by （Independent Review Center）IRC-assessed Progression Free Survival (PFS) per RECIST 1.1 as primary endpoint. Approximately 398 participants are estimated to be randomized into the study. Participants enrolled will be randomized to JMT101 or Cisplatin chemotherapy in a 1:1 manner, stratified by baseline brain metastasis (with/without) and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (0 versus 1).

Study Overview

• Status: Not yet recruiting
• Conditions: Local Advanced or Metastatic NSCLC
• Intervention / Treatment: Drug: JMT101 Injection; Drug: Osimertinib tablet; Drug: Cisplatin injection; Drug: Pemetrexed injection

• Study Type: Interventional
• Enrollment (Estimated): 398
• Phase: Phase 3

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age between 18-75 years old.
2. Histologically or cytologically confirmed diagnosis of NSCLC, locally advanced (Stage IIIB and IIIC according to the 8th edition of the IASLC TNM staging criteria) or metastatic (Stage IV), not suitable for curative therapy. For central laboratory confirmation of EGFR exon 20 insertion mutation with tumour tissue/blood sample.
3. At least 1 measurable lesion per RECIST Version 1.1
4. Life expectancy ≥ 12 weeks
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
6. Adequate organ and hematologic function

Exclusion Criteria:

1. Prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC.
2. Central nervous system metastasis with associated symptom and signs.
3. Concurrent EGFR mutations: exon 19 deletion, L858R, T790M, G719X, S768I, or L861Q.
4. History of interstitial lung disease, or infectious pneumonitis need heavy antibiotics therapy
5. As judged by the investigator, unsuitable for attending the 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: JMT101 combined with Osimertinib	Drug: JMT101 Injection; JMT101 Injection, 6 mg/kg intravenously, over 90 mins every 14 days; Drug: Osimertinib tablet; Osimertinib 160mg once po everyday
Active Comparator: Cisplatin combined with pemetrexed; Participants randomized into chemotherapy arm can receive up to 4 cycles of pemetrexed + cisplatin (pemetrexed 500 mg/m^2 + cisplatin 75mg/m^2, IV infusion, every 3 weeks) as the initial treatment. Participants whose disease has not progressed after 4 cycles of first-line platinum-based doublet chemotherapy may receive pemetrexed maintenance monotherapy until a treatment discontinuation criterion is met.	Drug: Cisplatin injection; Cisplatin 75mg/m^2, IV infusion, on day-1 at every cycle of 21days, 4 cycles at most.; Drug: Pemetrexed injection; Pemetrexed 500mg/m^2, IV infusion, on day-1 at every cycle of 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival (PFS) as assessed by Independent Review Center (IRC) per RECIST 1.1	Up to approximately 35 months after the first participant is randomized

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to approximately 35 months after the first participant is randomized
Overall Response Rate (ORR) by IRC per RECIST 1.1	Up to approximately 35 months after the first participant is randomized
Duration of Response (DoR) by IRC per RECIST 1.1	Up to approximately 35 months after the first participant is randomized
PFS by investigator per RECIST 1.1	Up to approximately 35 months after the first participant is randomized
ORR by investigator per RECIST 1.1	Up to approximately 35 months after the first participant is randomized
DoR by investigator per RECIST 1.1	Up to approximately 35 months after the first participant is randomized

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 26, 2024
• Primary Completion (Estimated): March 26, 2027
• Study Completion (Estimated): March 26, 2028

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Harboring EGFR 20ins mutation; Without prior systemic therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Tyrosine Kinase Inhibitors; Osimertinib; Pemetrexed
• Other Study ID Numbers: JMT101-012

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