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NCT03974022 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE1, PHASE2
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-01-29

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Part A Dose Escalation: Dose Limiting Toxicities (DLTs).

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outcome · POSTED

Part B: Objective Response Rate (ORR) According to RECIST 1.1 by an Independent Review Committee (IRC).

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outcome · POSTED

Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1

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outcome · POSTED

Part B: DoR, PFS According to RECIST 1.1 Using Assessments Performed by an IRC; DoR, PFS Using Investigators Assessments According to RECIST 1.1

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outcome · POSTED

Part B: AEs/SAEs

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outcome · POSTED

Part A: Confirmed ORR and DCR by Investigator.

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outcome · POSTED

Part A: DoR and PFS by Investigator.

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outcome · POSTED

Part A: Confirmed ORR and DCR by Independent Review Committee (IRC).

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outcome · POSTED

Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008

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outcome · POSTED

Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008

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outcome · POSTED

Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008

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outcome · POSTED

Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008

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outcome · POSTED

Part A Food Effect: Maximum Plasma Concentration (Cmax) of DZD9008

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outcome · POSTED

Part A Food Effect: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008

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outcome · POSTED

Part B: Maximum Plasma Concentration (Cmax) of DZD9008 and DZ0753

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outcome · POSTED

Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 and DZ0753.

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outcome · POSTED

Part B: Cmax,ss, at Steady State of DZD9008 and DZ0753

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outcome · POSTED

Part B: AUCss, at Steady State of DZD9008 and DZ0753.

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
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 previously treated and stable, neurologically asymptomatic and does not require corticosteroid treatment. 7. Adequate organ system function. 8. Part A Dose expansion: 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 dacomitinib, are allowed unless the patient had an objective response and subsequent progression assessed by the investigator. 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 the first administration of Sunvozertinib. 3. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before the first administration. 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 the first administration. 5. Receiving (or unable to stop using) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A within 1-2 weeks before the first administration. 6. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting Sunvozertinib with the exception of alopecia and grade 2 prior platinum-therapy related neuropathy. 7. Spinal cord compression or leptomeningeal metastasis. 8. 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, human immunodeficiency virus (HIV) and COVID-19 (per local practice). 9. Any of the following cardiac criteria: (1) Mean resting corrected QT interval (QTc) \> 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 QTF 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; (4) Prior history of atrial fibrillation within 6 months of first administration of Sunvozertinib, except prior drug treatment related and recovered. 10. 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. 11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Sunvozertinib. 12. History of hypersensitivity to active or inactive excipients of Sunvozertinib or drugs with a similar chemical structure or class to Sunvozertinib. 13. Women who are pregnant or breast feeding. 14. Involvement in the planning and conduct of the study. 15. 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.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Drug: Sunvozertinib
    label
    Part A Dose escalation
    type
    EXPERIMENTAL
  2. intervention Names
    1. Drug: Sunvozertinib
    label
    Part A Dose expansion cohort 1
    type
    EXPERIMENTAL
  3. intervention Names
    1. Drug: Sunvozertinib
    label
    Part A Dose expansion cohort 2
    type
    EXPERIMENTAL
  4. description
    Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy
    intervention Names
    1. Drug: Sunvozertinib
    label
    Part A Dose expansion cohort 3
    type
    EXPERIMENTAL
  5. description
    Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy
    intervention Names
    1. Drug: Sunvozertinib
    label
    Part A Dose expansion cohort 4
    type
    EXPERIMENTAL
  6. description
    Patients with EGFR Exon20ins, treatment naïve
    intervention Names
    1. Drug: Sunvozertinib
    label
    Part A Dose expansion cohort 5
    type
    EXPERIMENTAL
  7. intervention Names
    1. Drug: Sunvozertinib
    label
    Part A Dose expansion cohort 6
    type
    EXPERIMENTAL
  8. description
    Patients with EGFR Exon20ins
    intervention Names
    1. Drug: Sunvozertinib
    label
    Part B Dose extension cohort 1
    type
    EXPERIMENTAL
  9. description
    Patients with EGFR Exon20ins
    intervention Names
    1. Drug: Sunvozertinib
    label
    Part B Dose extension cohort 2
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Part A Dose escalation
    2. Part A Dose expansion cohort 1
    3. Part A Dose expansion cohort 2
    4. Part A Dose expansion cohort 3
    5. Part A Dose expansion cohort 4
    6. Part A Dose expansion cohort 5
    7. Part A Dose expansion cohort 6
    8. Part B Dose extension cohort 1
    9. Part B Dose extension cohort 2
    description
    Daily dose of Sunvozertinib
    name
    Sunvozertinib
    other Names
    1. DZD9008
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
315
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    To evaluate the safety and tolerability and defined the maximum tolerated dose (MTD) of sunvozertinib. DLT was evaluated in the DLT observation frame.
    measure
    Part A Dose Escalation: Dose Limiting Toxicities (DLTs).
    time Frame
    The DLT observation period is defined as the 28 days after the first multiple dose (up to 36 days from baseline).
  2. description
    To evaluate anti-tumor activity of Sunvozertinib in advanced NSCLC patients with EGFR Exon20 insertion at defined dose(s) by assessment of Objective Response Rate (ORR).
    measure
    Part B: Objective Response Rate (ORR) According to RECIST 1.1 by an Independent Review Committee (IRC).
    time Frame
    through the study completion, an average of around 1 year for part B
secondary Outcomes
  1. description
    To assess anti-tumor efficacy of Sunvozertinib using additional endpoints.
    measure
    Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1
    time Frame
    Through the study completion, an average of around 1 year for part B
  2. description
    To assess anti-tumor efficacy of Sunvozertinib using additional endpoints.
    measure
    Part B: DoR, PFS According to RECIST 1.1 Using Assessments Performed by an IRC; DoR, PFS Using Investigators Assessments According to RECIST 1.1
    time Frame
    Through the study completion, an average of around 1 year for part B
  3. description
    To determine the safety and tolerability of Sunvozertinib: Number of Participants With AEs, Number of Participants With SAEs. Using investigator reported AEs according to CTCAE and SAE criteria.
    measure
    Part B: AEs/SAEs
    time Frame
    Through the study completion, an average of around 1 year for part B
  4. description
    To assess preliminary anti-tumor activity of sunvozertinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. Confirmed ORR was defined as the percentage of patients achieving a CR (Complete Response) or PR (Partial Response) and was confirmed by subsequent tumor assessment at least 4 weeks within the study period. Confirmed DCR was defined as the proportion of patients with a best overall response of CR, PR, or SD. Patients who achieved a CR or PR must be confirmed by a subsequent tumor assessment at least 4 weeks within the study period. Patients who achieved a best overall response of SD must be confirmed by subsequent tumor assessment at least 35 days within the study period.
    measure
    Part A: Confirmed ORR and DCR by Investigator.
    time Frame
    The study duration was from the initiation of sunvozertinib treatment until the study completion. The median study duration was 10 months, and the maximal study duration was 51.4 months for part A.
  5. description
    To assess preliminary anti-tumor activity of sunvozertinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. DoR was presented for patients with confirmed objective response (CR or PR). DoR was the time from date of first documentation of CR or PR, which was subsequently confirmed, to date of first documentation of objective progression or death. Patients who had no documentation of objective progression or death was censored. PFS was the time from first dose date of sunvozertinib to date of first documentation of progression or death due to any cause, whichever occurred first. Patient who had no PFS event was censored.
    measure
    Part A: DoR and PFS by Investigator.
    time Frame
    The maximum median of DoR was 19.3 months, and the maximum median of PFS was 12.5 months for part A.
  6. description
    To retrospectively assess anti-tumor activity of sunvozertinib in treatment-naive NSCLC patients with EGFR Exon20ins according to RECIST 1.1 by IRC. Confirmed ORR was defined as the percentage of patients achieving a CR or PR and was confirmed by subsequent tumor assessment at least 4 weeks within the study period. Confirmed DCR was defined as the proportion of patients with a best overall response of CR, PR, or SD. Patients who achieved a CR or PR must be confirmed by subsequent tumor assessment at least 4 weeks within the study period. Patients who achieved a best overall response of SD must be confirmed by subsequent tumor assessment at least 35 days within the study period.
    measure
    Part A: Confirmed ORR and DCR by Independent Review Committee (IRC).
    time Frame
    The study duration was from the initiation of sunvozertinib treatment until the study completion. The median study duration was 10 months, and the maximal study duration was 51.4 months for part A.
  7. description
    Maximum observed plasma concentration (ng/mL), obtained directly from the observed concentration versus time data. Calculated for the single dose.
    measure
    Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008
    time Frame
    Cycle 0 Day 1: 0 (predose) up to 168 hours (for Part A escalation); Cycle 1 Day 1: 0 (predose) up to 24 hours (for Part A expansion)
  8. description
    Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule.
    measure
    Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008
    time Frame
    Cycle 0 Day 1: 0 (predose) up to 168 hours (for Part A escalation); Cycle 1 Day 1: 0 (predose) up to 24 hours (for Part A expansion)
  9. description
    Maximum observed plasma concentration(ng/mL), at steady state, obtained directly from the observed concentration versus time data. Calculated for the multiple dose.
    measure
    Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008
    time Frame
    Cycle 2 Day 1: 0 (predose) up to 24 hours (for Part A Dose expansion and expansion)
  10. description
    Area under the plasma concentration-time curve in the dose interval at steady state, calculated by the linear up/log down rule.
    measure
    Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008
    time Frame
    Cycle 2 Day 1: 0 (predose) up to 24 hours (for Part A Dose escalation and expansion)
  11. description
    Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose, in the fasted or fed state.
    measure
    Part A Food Effect: Maximum Plasma Concentration (Cmax) of DZD9008
    time Frame
    Day 1 and Day 9: 0 (predose) up to 168 hours.
  12. description
    Area under the plasma concentration-time-curve from time zero the last quantifiable time point, calculated by the linear up/log down rule, in the fasted or fed state.
    measure
    Part A Food Effect: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008
    time Frame
    Day 1 and Day 9: 0 (predose) up to 168 hours.
Full study description
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 Sunvozertinib 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).
Source references
references
  1. citation
    Yang JC, Wang M, Doucet L, Fan Y, Lv D, Sun M, Huang D, Greillier L, Planchard D, Hong Q, Mazieres J, Felip E, Li X, Hu Y, Fang J, Bazhenova L, Ghiringhelli F, Cobo Dols MA, Rodriguez LP, Bearz A, Pellini B, Kim YJ, Bosch-Barrera J, Shim BY, Luo YH, Tiseo M, Yang TY, Carcereny E, Memmott RM, Zalcman G, de Castro Carpeno J, Di Noia V, Parra HS, Streich G, Lee DH, Shum E, Han JY, Jaime JC, Brungs D, John T, D'Arcangelo M, Joaquin AB, Liu G, Antonuzzo L, Hinojal GF, Le X, Zheng L, Janne PA; WU-KONG1B. Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B). J Clin Oncol. 2025 Oct 10;43(29):3198-3208. doi: 10.1200/JCO-25-00788. Epub 2025 Sep 9.
    pmid
    40923280
    type
    DERIVED
  2. citation
    Miyamura BV, Mambetsariev I, Fricke J, Arias-Romero J, Cadman K, Shrestha S, Pisick E, Nguyen D, Malhotra J, Reyes A, Salgia R. Current paradigm of EGFRins20 in non-small cell lung cancer: A long way forward. Med. 2025 Sep 12;6(9):100803. doi: 10.1016/j.medj.2025.100803. Epub 2025 Aug 8.
    pmid
    40782807
    type
    DERIVED
  3. citation
    Luan T, Lin X, Xie X, Yang G, Wang S, Hao J, Zhou C. First case report of sunvozertinib for the treatment of HER2 exon 20 insertion in lung adenocarcinoma. Anticancer Drugs. 2024 Sep 1;35(8):757-760. doi: 10.1097/CAD.0000000000001628. Epub 2024 Jun 26.
    pmid
    38924456
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      occurrences
      1. context exact
        on for Zegfrovy will be posted on <a href="https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm">Drugs@FDA</a>.</p><p>Efficacy was evaluated in WU-KONG1B (NCT03974022), a multinational, open-label, dose randomization trial. Eligible patients had locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations with
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      source event date
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      /tmp/cancer-full-research/updates/pages/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20.html
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      source title
      FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations

    Preserved source evidence · Not medical advice