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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03974022
• Other study ID #: DZ2019E0001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 9, 2019
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: Dizal Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 315
• Est. completion date: July 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 dacomitinb, 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Sunvozertinib
Daily dose of Sunvozertinib

Locations

Country	Name	City	State
Argentina	Fundacion Respirar - Consultorios Medicos Dr. Doreski	Cabildo
Argentina	CEMIC Centro de Educación Médica e Investigaciones Clínicas - Hospital Universitario sede Saavedra	Ciudad Autónoma Buenos Aires
Argentina	Centro Medico Austral OMI	Ciudad Autónoma Buenos Aires
Argentina	Diabaid	Ciudad Autónoma Buenos Aires
Argentina	Fundacion CENIT Para La Investigacion en Neurociencias	Ciudad Autónoma Buenos Aires
Argentina	Instituto Argentino de Diagnositco y Tratamiento S.A.	Ciudad Autónoma Buenos Aires
Argentina	Instituto Medico de la Fundacion de Estudios Clínicos	Ciudad Autónoma Buenos Aires
Argentina	Centro de Investigación Pergamino SA	Pergamino
Argentina	Clinica Viedma S.A	Viedma
Australia	Blacktown Hospital	Blacktown
Australia	Chris O'Brien Lifehouse	Camperdown
Australia	Austin Hospital	Heidelberg
Australia	St George Hospital	Kogarah
Australia	Peter MacCallum Cancer Centre - East Melbourne	North Melbourne
Australia	Linear Cancer trials	Perth
Australia	Southern Medical Day Care Centre	Wollongong
Canada	Princess Margaret Cancer Centre	Toronto
Chile	Fundación Arturo López Pérez	Providencia
Chile	Orlandi Oncología - Centro Médico Health & Care	Santiago
Chile	SAGA	Santiago
Chile	James Lind Centro De Investigacion Del Cancer	Temuco
China	Beijing Cancer Hospital	Beijing
China	Beijing Chest Hospital,Capital Medical University	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	Hunan Cancer Hospital	Changsha
China	West China Hospital of Sichuan University	Chengdu
China	Chongqing Cancer Hospital	Chongqing
China	Fujian Cancer Hospital	Fuzhou
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou
China	Hainan General Hospital	Haikou
China	The First Affilated Hospital of Zhejiang University	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	The first Affiliated Hospital of USTC Anhui Provincial Hospital	Hefei
China	The Second Hospital of Anhui Medical University	Hefei
China	Henan Cancer Hospital	Henan
China	The Affiliated Hospital of Inner Mongolia Medical University	Hohhot
China	The Affiliated Huaian No.1 Peoples Hospital of Nanjing Medical University	Huai'an
China	Jinan Central Hospital	Jinan
China	Linyi Cancer Hospital	Linyi
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	The Second Affiliated Hospital of Nanchang University	Nanchang
China	Guangxi Medical University Cancer Hospital	Nanning
China	Zhongshan Hospital, Fudan University	Shanghai
China	The First Hospital of China Medical University	Shenyang
China	Shanxi Cancer Hospital	Taiyuan
China	Taizhou Hospital of Zhejiang Province	Taizhou
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	Hubei Cancer Hospital	Wuhan
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
France	Centre Hospitalier Universitaire d'Angers	Angers
France	Hospices Civils de Lyon - Hôpital Louis Pradel	Bron
France	Centre Georges François Leclerc	Dijon
France	CHU de Lille - Institut Coeur Poumons	Hellemmes Lille
France	Hôpital de La Timone AP-Hm	Marseille
France	CHU de Montpellier Hôpital Arnaud de Villeneuve	Montpellier
France	APHP-Hôpital Bichat - Claude Bernard	Paris
France	CHU de Poitiers	Poitiers
France	Institut de Cancérologie de l'Ouest	Saint-Herblain
France	HIA Begin	Saint-Mandé
France	CHU de Toulouse - Hôpital Larrey	Toulouse
France	Institut Gustave ROUSSY	Villejuif
Italy	Centro di Riferimento Oncologico (CRO)	Aviano
Italy	Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"	Catania
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST IRCCS	Meldola
Italy	Istituto Europeo di Oncologia	Milano
Italy	Azienda Ospedaliero-Universitaria di Parma	Parma
Italy	AUSL Romagna - Ospedale S.M delle Croci	Ravenna
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Istituti Fisioterapici Ospitalieri	Roma
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama-shi
Japan	Aichi Cancer Center Hospital	Nagoya-Shi
Japan	Niigata University Medical & Dental Hospital	Niigata-Shi
Japan	Okayama University Hospital	Okayama-Shi
Japan	Tokushima University Hospital	Tokushima-Shi
Japan	Tokyo Shinagawa Hospital	Tokyo
Korea, Republic of	Chungbuk National University Hospital	Cheonju
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon
Malaysia	Hospital Sultan Ismail	Johor Bahru
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	ICO (Institut Catala d'Oncologia) Badalona - Hospital Germans Trias i Pujol	Barcelona
Spain	Institut Català d'Oncología de Girona - Hospital Universitari de Girona Dr. Josep Trueta	Girona
Spain	Hospital de Jeréz	Jerez de la Frontera
Spain	Centro Integral Oncológico Clara Campal (CIOCC)	Madrid
Spain	Clínica Universidad de Navarra	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital La Fe	Valencia
Taiwan	Chi Mei Hospital, Liouying	Liuying
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Wan Fang Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital	Taoyuan
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Michigan Center of Medical Research	Farmington Hills	Michigan
United States	University of California, San Diego (UCSD) - Moores Cancer Center	La Jolla	California
United States	Northwell Health - Centers for Advanced Medicine	New Hyde Park	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center	Orange	California
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Innovative Clinical Research Institute, LLC	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Dizal Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  China,  France,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Safety and tolerability of Sunvozertinib.	To investigate the safety and tolerability of Sunvozertinib 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 Sunvozertinib when given orally in patients with advanced NSCLC with EGFR or HER2 mutations.	28 days after the first multiple dose
Primary	Part B: Objective Response Rate (ORR) according to RECIST 1.1 by an Independent Review Committee (IRC).	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).	through the study completion, an average of around 1 year
Secondary	Part A: Plasma and urine Sunvozertinib concentrations, and derived PK parameters.	To characterize the pharmacokinetics (PK) of Sunvozertinib following a single oral dosing and at steady state after multiple oral dosing in the fasted state, and renal excretion of Sunvozertinib.	Through cycle 3 day 1 (8 days for Cycle 0, 28 days for Cycle 1, then 21 days for each subsequent cycle)
Secondary	Part A: Plasma Sunvozertinib concentrations, and derived PK parameters	To evaluate the effect of food on the exposure of Sunvozertinib at the defined doses.	Through the study completion
Secondary	Part A: ORR, BOR, DoR, DCR, %change in size of tumor lesion, PFS by investigator.	To assess preliminary anti-tumor activity of Sunvozertinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator.	Through the study completion
Secondary	Part A: ORR, DCR, DoR by IRC.	To retrospectively assess anti-tumor activity of Sunvozertinib in patients with EGFR Exon20ins according to RECIST 1.1 by an Independent Review Committee (IRC).	Through the study completion
Secondary	Part B: DoR, PFS, DCR, BOR and % of change in size of tumor lesion according to RECIST 1.1 using assessments performed by an IRC; DoR, PFS, DCR, BOR and % of change in size of tumor lesion using investigators assessments accord.	To assess anti-tumor efficacy of Sunvozertinib using additional endpoints.	Through the study completion
Secondary	Part B: AEs/SAEs; Laboratory data; vital signs; physical examination; ECG; echocardiogram/MUGA; pulmonary function test.	To determine the safety and tolerability of Sunvozertinib.	Through the study completion
Secondary	Part B: Plasma Sunvozertinib and metabolite concentration and derived PK parameters if deemed appropriately.	To characterize the PK of Sunvozertinib.	Through the study completion