DZD9008 in Pretreated Lung Cancer Patients With EGFR Exon20 Insertion Mutation

• ClinicalTrials.gov Identifier: NCT05712902
• Recruitment Status: Active, not recruiting
• First Posted: February 6, 2023
• Last Update Posted: February 6, 2023
• Sponsor: Dizal Pharmaceuticals
• Information provided by (Responsible Party): Dizal Pharmaceuticals

Tracking Information

• First Submitted Date: January 12, 2023
• First Posted Date: February 6, 2023
• Last Update Posted Date: February 6, 2023
• Actual Study Start Date: July 19, 2021
• Actual Primary Completion Date: October 17, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 26, 2023): Objective Response Rate (ORR) according to RECIST 1.1 by an Independent Review Committee (IRC) [ Time Frame: From first dosing until disease progression or intolerable adverse events ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DZD9008 in Pretreated Lung Cancer Patients With EGFR Exon20 Insertion Mutation
• Official Title: A Phase II, Single Arm, Multicenter Study to Evaluate Anti-tumor Activity, Safety, Tolerability and Pharmacokinetics of DZD9008 in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutation
• Brief Summary: This is a Phase II, single-arm, multi-center clinical study to evaluate the anti-tumor efficacy, safety, tolerability and pharmacokinetics of DZD9008 in participants with locally advanced or metastatic NSCLC carrying EGFR exon 20 insertion mutations whose disease has progressed on prior platinum-based chemotherapy
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

Drug: DZD9008

Daily dose of DZD9008

Study Arms

Experimental: Daily dose of DZD9008

Intervention: Drug: DZD9008

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 26, 2023): 104
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: May 6, 2024
• Actual Primary Completion Date: October 17, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients must be able to understand the nature of the trial and provide a signed and dated, written informed consent form.
2. Aged at least 18 years old.
3. Histological or cytological confirmed locally advanced or metastatic NSCLC
4. Tumor tissue EGFR exon 20 insertion mutations confirmed by qualified local laboratories or sponsor-designated central laboratories.
5. Participants must exhibit Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 at ICF signature with no deterioration over the past 2 weeks.
6. Predicted life expectancy ≥ 12 weeks.
7. Patient must have measurable disease according to RECIST 1.1.
8. Patients with brain metastasis (BM) can only be enrolled under the condition that BM is previously treated and stable.
9. Adequate organ system functions.
10. Patients should receive at least one line but no more than three lines of prior systemic therapy (at least one line must contain platinum-based therapy).

Exclusion Criteria:

1. Prior malignancy within 2 years requires active treatment, except for adequately treated basal cell skin carcinoma, in situ cervical carcinoma, or other cancer types (to be discussed with Dizal's Study Physician) who has been disease free for > 2 years with life expectancy >2 years.
2. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting DZD9008 with the exception of alopecia and grade 2 prior platinum-therapy related neuropathy.
3. Spinal cord compression or leptomeningeal metastasis.
4. History of stroke or intracranial hemorrhage within 6 months before first administration of DZD9008.
5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses.
6. Active infection including hepatitis B, hepatitis C, human immunodeficiency virus (HIV) and COVID-19.

7. Any of the following cardiac criteria:

   • Mean resting corrected QT interval (QTc) > 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 QTc 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.
8. Participants with hemorrhagic diseases such as von Willebrand disease.
9. 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 or immunotherapy induced immune pneumonia.
10. 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.

11. Prior/concomitant therapy

    1. Patients who have received prior Poziotinib, TAK-788, CLN-081 or BDTX-189, furmonertinib or any other EGFR/HER2 exon20ins small molecule inhibitors treatment should be excluded.
    2. Other EGFR TKIs, such as gefitinib, erlotinib, osimertinib, afatinib, dacomitinb are not considered EGFR or HER2 Exon20ins small molecule inhibitors, and thus prior treatment with these drugs is allowed unless the patient had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.
    3. Treatment with antibodies within 4 weeks before first administration of DZD9008.
    4. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before first administration of DZD9008.
12. Women who are pregnant or breast feeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05712902
• Other Study ID Numbers: DZ2020E0001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Dizal Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Dizal Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mengzhao Wang; Peking Union Medical College Hospital

• PRS Account: Dizal Pharmaceuticals
• Verification Date: January 2023