Assessing an Oral EGFR Inhibitor, DZD9008 in Patients With Advanced Non-small Cell Lung Cancer(NSCLC) With EGFR Mutations (WU-KONG15)

NCT05559645 | Recruiting

• 1 other identifier: DZ2021E0006
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single center cohort study to access the anti-tumor efficacy, safety and tolerability of DZD9008 in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) sensitizing mutations and EGFR uncommon mutations who have progressed following standard TKI therapy, and in treatment naive patients with NSCLC harboring EGFR Exon20 insertion mutation and EGFR sensitizing mutations.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  To assess anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator

  through study completion, an average of 1 year

Secondary Outcomes (1)

• Duration of Response (DoR)

  through study completion, an average of 1 year

Other Outcomes (7)

• Disease Control rate (DCR)

  through study completion, an average of 1 year

• Objective Response Rate (ORR)

  through study completion, an average of 1 year

• Overall survival (OS)

  through study completion, an average of 1 year

Study Arms (7)

Cohort 1: EGFR sensitizing mutations, T790M neg

EXPERIMENTAL

Drug: DZD9008

Cohort 2: EGFR sensitizing mutations

EXPERIMENTAL

Drug: DZD9008

Cohort 3: EGFR uncommon mutations

EXPERIMENTAL

Drug: DZD9008

Cohort 4: EGFR Exon20ins

EXPERIMENTAL

Drug: DZD9008

Cohort 5: EGFR sensitizing mutations

EXPERIMENTAL

Drug: DZD9008

Cohort 6: EGFR sensitizing mutations,T790M pos

EXPERIMENTAL

Drug: DZD9008

Cohort 7: EGFR Exon20ins treatment naive

EXPERIMENTAL

Drug: DZD9008

Interventions

DZD9008 DRUG

Daily dosing of DZD9008 200mg

Cohort 1: EGFR sensitizing mutations, T790M neg; Cohort 2: EGFR sensitizing mutations; Cohort 3: EGFR uncommon mutations; Cohort 4: EGFR Exon20ins; Cohort 5: EGFR sensitizing mutations; Cohort 6: EGFR sensitizing mutations,T790M pos

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To provide a signed and dated, written informed consent.
• Aged ≥ 18 years old
• Histologically or cytologically confirmed locally advanced or metastatic NSCLC with documented EGFR mutations from a local laboratory
• ECOG performance status 0-1.
• Predicted life expectancy ≥ 12 weeks
• Patient must have measurable disease according to RECIST 1.1.
• Patient who has progressed or intolerant to standard therapy (except treatment naïve patients in Cohort 4 and Cohort 7: with EGFR Exon20ins; and in Cohort 5 with EGFR sensitizing mutation).
• Patients with brain metastasis (BM) can be enrolled under the condition that BM is stable, neurologically asymptomatic and does not require corticosteroid treatment.
• Adequate organ system function.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x ULN if no liver metastases or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN if no liver metastases or ≤ 5 x ULN with liver metastases
• Creatinine ≤ 1.5 x ULN, concurrent with calculated or measured creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault method or ≥ 50 mL/min in 24 hours

You may not qualify if:

• Known history of bleeding diathesis.
• Prior malignancy within 2 years requires active treatment.
• Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of first administration.
• History of stroke or intracranial haemorrhage within 6 months before the first administration.
• Spinal cord compression or leptomeningeal metastasis.
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTcF) \> 470 msec obtained from 3 electrocardiograms (ECGs);
• Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third degree heart block, and second-degree heart block, PR interval \> 250 msec.
• Any factors that increase the risk of QTcF prolongation, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.
• Prior history of atrial fibrillation within 6 months of first administration of DZD9008, except prior drug treatment related and recovered.
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of DZD9008.
• History of hypersensitivity to active or inactive excipients of DZD9008 or drugs with a similar chemical structure or class to DZD9008.
• Women who are pregnant or breast feeding.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Dizal (Jiangsu) Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Yan Xu, Dr.

CONTACT

010-69155039; maraxu@163.com

Mengzhao Wang

CONTACT

010-69155039; mengzhaowang@sina.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Director of Department of Respiratory and Critical Care Medicine

Study Record Dates

• First Submitted: July 30, 2022
• First Posted: September 29, 2022
• Study Start: November 18, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)