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Assessing an Oral EGFR Inhibitor, DZD9008 in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)

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ClinicalTrials.gov Identifier: NCT03974022
Recruitment Status : Recruiting
First Posted : June 4, 2019
Last Update Posted : January 12, 2023
Sponsor:
Information provided by (Responsible Party):
Dizal Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 21, 2019
First Posted Date  ICMJE June 4, 2019
Last Update Posted Date January 12, 2023
Actual Study Start Date  ICMJE July 9, 2019
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2019)
  • Part A: Safety and tolerability of DZD9008. [ Time Frame: 28 days after the first multiple dose ]
    To investigate the safety and tolerability of DZD9008 when given orally to patients with advanced NSCLC with EGFR or HER2 mutations; To establish Maximum Tolerated Dose (MTD) (if possible) and Recommended Phase 2 Dose (PR2D) of DZD9008 when given orally in patients with advanced NSCLC with EGFR or HER2 mutations.
  • Part B: Objective Response Rate (ORR) according to RECIST 1.1. [ Time Frame: through the study completion, an average of around 1 year ]
    To evaluate anti-tumor activity of DZD9008 in advanced NSCLC patients with EGFR Exon20 insertion, HER2 Exon20 insertion or EGFR uncommon mutations at defined dose(s) (Part B)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2019)
Plasma DZD9008 concentration [ Time Frame: Through cycle 3 day 1 (8 days for Cycle 0, 28 days for Cycle 1, then 21 days for each subsequent cycle) ]
To characterize the pharmacokinetics (PK) of DZD9008 following a single oral dosing and at steady state after multiple oral dosing, and renal excretion of DZD9008
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessing an Oral EGFR Inhibitor, DZD9008 in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)
Official Title  ICMJE A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of DZD9008 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) With EGFR or HER2 Mutation
Brief Summary This study will treat patients with advanced NSCLC with EGFR or HER2 mutation who have progressed following prior therapy. This is the first time this drug is tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and preliminarily assess its anti-cancer activity as monotherapy.
Detailed Description A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of DZD9008 in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR or HER2 mutation. This study includes dose escalation, dose expansion, food effect (Part A) and dose extension (Part B).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: DZD9008
Daily dose of DZD9008
Study Arms  ICMJE
  • Experimental: Part A Dose escalation
    Intervention: Drug: DZD9008
  • Experimental: Part A Dose expansion cohort 1
    Intervention: Drug: DZD9008
  • Experimental: Part A Dose expansion cohort 2
    Intervention: Drug: DZD9008
  • Experimental: Part A Dose expansion cohort 3
    Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy
    Intervention: Drug: DZD9008
  • Experimental: Part A Dose expansion cohort 4 (Ongoing)
    Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy
    Intervention: Drug: DZD9008
  • Experimental: Part A Dose expansion cohort 5 (Ongoing)
    Patients with EGFR Exon20ins, treatment naïve
    Intervention: Drug: DZD9008
  • Experimental: Part A Dose expansion cohort 6
    Intervention: Drug: DZD9008
  • Experimental: Part B Dose extension (Ongoing)
    Patients with EGFR Exon20ins should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease.
    Intervention: Drug: DZD9008
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2022)
336
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2019)
160
Estimated Study Completion Date  ICMJE July 2024
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Aged at least 18 years old, be able to provide a signed and dated, written informed consent.
  2. With documented histological or cytological confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations.
  3. (ECOG) performance status 0-1.
  4. Predicted life expectancy ≥ 12 weeks
  5. Patient must have measurable disease according to RECIST 1.1.
  6. Patients with brain metastasis (BM) can be enrolled under the condition that BM is stable, neurologically asymptomatic and does not require corticosteroid treatment.
  7. Adequate organ system function.

    Part A Dose expansion:

  8. Dose expansion cohort 5: NSCLC patients with EGFR Exon20ins, who have not received prior systemic therapy (treatment naïve).

    Part B dose extension:

  9. Patients must have histologically or cytologically confirmed locally advanced or metastatic NSCLC with documented EGFR Exon20ins mutation in tumor tissue from a local CLIA-certified laboratory (or equivalent) or Sponsor designated central laboratory prior to the study entry.
  10. Patients should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease.

Exclusion Criteria:

  1. For part B: Patients who have received prior treatment with Poziotinib or TAK788 or other EGFR/HER2 exon20 insertion inhibitors should be excluded. Prior treatment with currently approved EGFR TKIs for sensitizing or T790M resistance mutations, such as gefitinib, erlotinib, osimertinib, afatinib and dacomitinb, are allowed.
  2. Treatment with EGFR or HER2 antibodies, major surgery (excluding placement of vascular access), or onco-immunotherapy (e.g. immune checkpoint inhibitors PD-1, PD-L1, CTLA-4) within 4 weeks before screening.
  3. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before screening.
  4. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose or with a wide field of radiation which must be completed within 4 weeks before screening.
  5. Receiving (or unable to stop using) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A within 2-3 weeks before screening.
  6. Grapefruit, grapefruit juice, and orange marmalade (made with Seville oranges) within 1 week before screening.
  7. 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.
  8. Spinal cord compression or leptomeningeal metastasis.
  9. 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).
  10. Any of the following cardiac criteria: (1) Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs); (2) 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. (3) 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
  11. 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
  12. 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
  13. History of hypersensitivity to active or inactive excipients of DZD9008 or drugs with a similar chemical structure or class to DZD9008
  14. Women who are pregnant or breast feeding
  15. Involvement in the planning and conduct of the study.
  16. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Li Zheng, M.D & Ph. D 86-21-61097899 li.zheng@dizalpharma.com
Contact: Pamela Yang, M.D & Ph. D 86-21-61097866 pamela.yang@dizalpharma.com
Listed Location Countries  ICMJE Australia,   France,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03974022
Other Study ID Numbers  ICMJE DZ2019E0001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Dizal Pharmaceuticals
Original Responsible Party Dizal (Jiangsu) Pharmaceutical Co., Ltd.
Current Study Sponsor  ICMJE Dizal Pharmaceuticals
Original Study Sponsor  ICMJE Dizal (Jiangsu) Pharmaceutical Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pasi Antero Janne, M.D & Ph. D Dana-Farber Cancer Institute
PRS Account Dizal Pharmaceuticals
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP