Study 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).

Condition or Disease	Intervention/Treatment
Non-Small Cell Lung Cancer	Drug: Sunvozertinib

Study Design

Study Type	Interventional
Actual Enrollment	315 participants
Design Allocation	Non-Randomized
Interventional Model	Single Group Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
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
Study Start Date	July 9, 2019
Anticipated Primary Completion Date	July 2024
Anticipated Study Completion Date	July 2025

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Part A Dose escalation	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part A Dose expansion cohort 1	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part A Dose expansion cohort 2	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part A Dose expansion cohort 3 Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part A Dose expansion cohort 4 Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part A Dose expansion cohort 5 Patients with EGFR Exon20ins, treatment naïve	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part A Dose expansion cohort 6	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part B Dose extension cohort 1 Patients with EGFR Exon20ins	Drug: Sunvozertinib Daily dose of Sunvozertinib
Part B Dose extension cohort 2 Patients with EGFR Exon20ins	Drug: Sunvozertinib Daily dose of Sunvozertinib

Outcome Measures

Primary Outcome Measures

1. Part A: Safety and tolerability of Sunvozertinib. [28 days after the first multiple dose]
   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.
2. Part B: Objective Response Rate (ORR) according to RECIST 1.1 by an Independent Review Committee (IRC). [through the study completion, an average of around 1 year]
   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).

Secondary Outcome Measures

1. Part A: Plasma and urine Sunvozertinib concentrations, and derived PK parameters. [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 Sunvozertinib following a single oral dosing and at steady state after multiple oral dosing in the fasted state, and renal excretion of Sunvozertinib.
2. Part A: Plasma Sunvozertinib concentrations, and derived PK parameters [Through the study completion]
   To evaluate the effect of food on the exposure of Sunvozertinib at the defined doses.
3. Part A: ORR, BOR, DoR, DCR, %change in size of tumor lesion, PFS by investigator. [Through the study completion]
   To assess preliminary anti-tumor activity of Sunvozertinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator.
4. Part A: ORR, DCR, DoR by IRC. [Through the study completion]
   To retrospectively assess anti-tumor activity of Sunvozertinib in patients with EGFR Exon20ins according to RECIST 1.1 by an Independent Review Committee (IRC).
5. 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. [Through the study completion]
   To assess anti-tumor efficacy of Sunvozertinib using additional endpoints.
6. Part B: AEs/SAEs; Laboratory data; vital signs; physical examination; ECG; echocardiogram/MUGA; pulmonary function test. [Through the study completion]
   To determine the safety and tolerability of Sunvozertinib.
7. Part B: Plasma Sunvozertinib and metabolite concentration and derived PK parameters if deemed appropriately. [Through the study completion]
   To characterize the PK of Sunvozertinib.

Eligibility Criteria

Ages Eligible for Study	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	Aged at least 18 years old, be able to provide a signed and dated, written informed consent. With documented histological or cytological confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations. (ECOG) performance status 0-1. Predicted life expectancy ≥ 12 weeks Patient must have measurable disease according to RECIST 1.1. 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. Adequate organ system function. 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: 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. Patients should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease.
Exclusion Criteria	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. 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. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before the first administration. 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. 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. 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. Spinal cord compression or leptomeningeal metastasis. 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). 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. 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. 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. History of hypersensitivity to active or inactive excipients of Sunvozertinib or drugs with a similar chemical structure or class to Sunvozertinib. Women who are pregnant or breast feeding. Involvement in the planning and conduct of the study. 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.

Contacts and Locations

Sponsors and Collaborators	Dizal Pharmaceuticals
Locations	University of California, San Diego (UCSD) - Moores Cancer Center | La Jolla, California, United States, 92093 University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center | Orange, California, United States, 92868 Innovative Clinical Research Institute, LLC | Whittier, California, United States, 90603-2137 University of Colorado Hospital - Anschutz Cancer Pavilion | Aurora, Colorado, United States, 80045 H. Lee Moffitt Cancer Center & Research Institute | Tampa, Florida, United States, 33612 Dana-Farber Cancer Institute | Boston, Massachusetts, United States, 02215 Michigan Center of Medical Research | Farmington Hills, Michigan, United States, 48334 Northwell Health - Centers for Advanced Medicine | New Hyde Park, New York, United States, 11042-1118 Laura and Isaac Perlmutter Cancer Center | New York, New York, United States, 10016 Icahn School of Medicine at Mount Sinai | New York, New York, United States, 10029 The Ohio State University Comprehensive Cancer Center | Columbus, Ohio, United States, 43210-1240 Virginia Cancer Specialists | Fairfax, Virginia, United States, 22031 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, Argentina, 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, Australia, Princess Margaret Cancer Centre | Toronto, Canada, 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, Chile, 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, China, 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, France, 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, Italy, 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, Japan, 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, Korea, Republic of, Hospital Sultan Ismail | Johor Bahru, Malaysia, Hospital Kuala Lumpur | Kuala Lumpur, Malaysia, University Malaya Medical Centre | Kuala Lumpur, Malaysia, 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, Spain, 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, Taiwan,
Investigators	Principal Investigator: Pasi Antero Jänne, M.D & Ph. D, Dana-Farber Cancer Institute

More Information

Additional Relevant MeSH Terms

• Lung Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Respiratory Tract Neoplasms
• Thoracic Neoplasms
• Neoplasms by Site
• Neoplasms
• Lung Diseases
• Respiratory Tract Diseases
• Carcinoma, Bronchogenic
• Bronchial Neoplasms