A Study of DZD9008 Versus Platinum-Based Doublet Chemotherapy in Local Advanced or Metastatic Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a phase 3, open-label, randomized, multi-center study assessing the efficacy and safety of DZD9008 versus platinum-based doublet chemotherapy in participants with locally advanced or metastatic NSCLC with EGFR Exon20ins mutation, who are newly diagnosed or have not received prior systemic therapy in advanced stage. Primary objective of this study is to assess the efficacy of DZD9008 versus platinum-based doublet chemotherapy using by BICR-assessed PFS per RECIST 1.1 as primary endpoint. Approximately 320 participants are estimated to be randomized into the study. Participants enrolled will be randomized to DZD9008 or platinum-based doublet chemotherapy in a 1:1 manner, stratified by baseline brain metastasis (with/without).

Official Title
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A Phase 3, Open-Label, Randomized, Multi-Center Study of DZD9008 Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 20 Insertion Mutation

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: DZD9008
* Drug: Pemetrexed+carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged at least 18 years old (or per local regulatory/IRB requirement). Histologically or cytologically confirmed diagnosis of non-squamous NSCLC, locally advanced (Stage IIIB and IIIC according to the 8th edition of the AJCC TNM staging criteria) or metastatic (Stage IV), not suitable for curative therapy. Adequate tumor tissue available, for central laboratory confirmation of EGFR exon 20 insertion mutation At least 1 measurable lesion per RECIST Version 1.1 Life expectancy ≥ 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Adequate organ and hematologic function Exclusion Criteria: Prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC. Spinal cord compression or leptomeningeal metastasis. Concurrent EGFR mutations: exon 19 deletion, L858R, T790M, G719X, S768I, or L861Q. History of stroke or intracranial hemorrhage within 6 months before randomization. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses (i.e., hemophilia and Von Willebrand disease).

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DZD9008<br> | Drug: DZD9008<br>* orally, 300 mg, once daily until a treatment discontinuation criterion is met.<br>|
| Active Comparator: Platinum-based Chemotherapy<br> | Drug: Pemetrexed+carboplatin<br>* Participants randomized into chemotherapy arm can receive up to 6 cycles of pemetrexed + carboplatin (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve 5 mg/ml per minute (AUC5), 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 |  | Up to approximately 34 months after the first participant is randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Up to approximately 34 months after the first participant is randomized |