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

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

Tracking Information

• First Submitted Date: May 21, 2019
• First Posted Date: June 4, 2019
• Last Update Posted Date: January 12, 2023
• Actual Study Start Date: July 9, 2019
• Estimated Primary Completion Date: October 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; 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: 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2022): 336
• Original Estimated Enrollment (submitted: June 3, 2019): 160
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: October 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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: Australia, France, Italy, Japan, Korea, Republic of, Malaysia, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT03974022
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Dizal Pharmaceuticals
• Original Responsible Party: Dizal (Jiangsu) Pharmaceutical Co., Ltd.
• Current Study Sponsor: Dizal Pharmaceuticals
• Original Study Sponsor: Dizal (Jiangsu) Pharmaceutical Co., Ltd.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pasi Antero Janne, M.D & Ph. D; Dana-Farber Cancer Institute

• PRS Account: Dizal Pharmaceuticals
• Verification Date: September 2022