Efficacy and Safety of JMT101 Combined With Afatinib (or Osimertinib) in Patients With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study is a Phase Ib, open label, multi-center study of to evaluate the safety and efficacy of JMT101 combined with EGFR-TKIs (Afatinib or Osimertinib) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.

Detailed Description
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The objective of the trial is to evaluate the safety and efficacy of JMT101 combined with EGFR-TKIs (afatinib or osimertinib) in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. This study consists of two parts (Stage I and Stage II). Stage I was a dose escalation study, and Stage II was a dose expansion study.

Official Title
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A Phase Ib,Open Label,Multi-center Study to Assess the Efficacy and Safety of JMT101 Combined With Afatinib (or Osimertinib) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations

Conditions
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Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: JMT101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically or cytologically confirmed, locally advanced or metastatic NSCLC, harboring an EGFR exon 20 insertion mutation. ( non-irradiable, non-operable); No previous treatment or first-line treatment failed NSCLC; At least 1 measurable lesion according to RECIST 1.1; ECOG score 0 or 1; Exclusion Criteria: Previously treated with EGFR antibody; Symptomatic brain metastasis; Interstitial pneumopathy; Known hypersensitivity to any ingredient of JMT101, afatinib, osimertinib or their excipients; Receiving an investigational product in another clinical study within 4 weeks; History of serious systemic diseases; History of serious autoimmune diseases; Pregnancy or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort<br>Two dose levels of JMT101 combined with afatinib or osimertinib will be tested according to the 3 + 3 dose-escalation design. The dose-limiting toxicity (DLT) will be assessed from the first administration to the end of the first cycle (28 days). | Drug: JMT101<br>* IV infusion Q2W for 4 weeks (28-day cycles)<br>* Other names: Afatinib or Osimertinib;|
| Experimental: Dose Expansion Cohort<br>Once the effective dose has been determined, an expansion cohort will be opened to evaluate the efficacy and safety of the selected dose. | Drug: JMT101<br>* IV infusion Q2W for 4 weeks (28-day cycles)<br>* Other names: Afatinib or Osimertinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)). |  | From enrollment until 30 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1 |  | From first dose to disease progression or end of study, an average of 1 year | 
| Disease control rate (DCR). |  | From first dose to disease progression or end of study, an average of 1 year | 
| Progression free survival (PFS). |  | From first dose to disease progression or end of study, an average of 1 year | 
| Overall survival (OS). |  | From first dose to death or end of study, an average of 1 year | 
| Area under the concentration curve from time 0 to the concentration at last time point (AUC0-last) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Maximum measured plasma concentration (Cmax) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Time to maximum plasma concentration (Tmax) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Half-life (T1/2) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Immunogenicity profile of JMT101. | Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies and neutralizing antibodies. | From enrollment until 30 days after the last dose | 
| Potential biomarkers detected in plasma circulating tumor DNA. |  | From enrollment up to disease progression, an average of 1 year |