A Prospective Cohort Study of Zorifertinib as a First-line Treatment in Patients With Epidermal Growth Factor Receptor-mutant Advanced Non-small Cell Lung Cancer With Central Nervous System (CNS) Metastases

NCT07143045 | Recruiting

• 1 other identifier: AZD3759-CIT-401
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 34

Brief Summary

This study is a patient-centered, two-group, three-cohort, multi-center, prospective study to further evaluate the survival benefits and safety of zorifertinib as a first-line treatment in EGFRm+ advanced NSCLC patients with CNS metastases, and to compare the clinical value of zorifertinib with other epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).

Conditions

EGFR Mutant Advanced Non-small Cell Lung Cancer; Central Nervous System (CNS) Metastases

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  The period from the first administration date of the study treatment to the date of death due to any cause.

  up to 36 months

Secondary Outcomes (5)

• Incidence of Adverse Events (AEs) for zorifertinib

  up to 36 months

• Incidence of Dose Adjustments for zorifertinib

  up to 36 months

• Progression-free survival (PFS)

  every 8 weeks,up to 36 months

• intracranial Progression-free survival (iPFS)

  every 8 weeks,up to 36 months

• Objective Response Rate (ORR)

  every 8 weeks, up to 36 months

Other Outcomes (2)

• The progression-free survival period of the zorifertinib treatment group (PFS2)

  every 8 weeks, up to 36 months

• The Genetic Resistance Status

  up to 36 months

Study Arms (3)

Cohort A

Patients who receive first-line zorifertinib and meet the inclusion/exclusion criteria of the EVEREST study (the EVEREST study is a randomized, open-label, multi-center, Phase II/III study to compare the efficacy and safety of first-line zorifertinib versus gefitinib/erlotinib in EGFR-mutant advanced NSCLC patients with CNS metastases)

Drug: zorifertinib

Cohort B

Patients who receive first-line zorifertinib but do not meet the inclusion/exclusion criteria of the EVEREST study (the EVEREST study is a randomized, open-label, multi-center, Phase II/III study to compare the efficacy and safety of first-line zorifertinib versus gefitinib/erlotinib in EGFR-mutant advanced NSCLC patients with CNS metastases)

Drug: zorifertinib

Cohort C

Patients who receive various other anti-tumor drugs selected by the clinician, excluding zorifertinib, as first-line treatment.

Interventions

zorifertinib DRUG

Cohort A and B will receive zorifertinib as first line treatment

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with advanced non-small cell lung cancer (NSCLC) who have been diagnosed with epidermal growth factor receptor mutation type (EGFRm+) and have central nervous system (CNS) metastasis

You may qualify if:

• Male or female, aged ≥18 years.
• Histologically or cytologically confirmed NSCLC with EGFR sensitizing mutations (including L858R or Exon 19Del), ineligible for curative surgery or radiotherapy.
• CNS metastases diagnosed as brain metastases (BM) and/or leptomeningeal metastases (LM) by imaging and/or cerebrospinal fluid pathological examination.
• Planning to receive zorifertinib (zorifertinib group) or other anti-tumor treatments (other treatment group) as first-line treatment.
• Voluntarily agreeing to participate in this study and signing the informed consent form.

You may not qualify if:

• Currently participating or planning to participate in any interventional clinical study for first-line treatment (patients who have participated in non-interventional, real-world studies may still be included).
• Other reasons that, in the Investigator's opinion, make the patient unsuitable for this study.
• No prior treatment with chemotherapy, EGFR-TKIs, biological therapy, immunotherapy, or any investigational drug that is considered first line treatment for advanced NSCLC.
• Eligible patients are not candidates for definitive surgical resection or radiation of all lesions in the opinion of the treating physician.
• All patients must be stable without any systemic (oral or parenteral) corticosteroid or anticonvulsant therapy for at least 2 weeks prior to study treatment. Inhaled non-absorbable and topical corticosteroid use are permitted as indicated.
• Patients may have prior placement of a properly functioning CNS shunt or Ommaya reservoir.
• ECOG performance status 0 or 1, with no deterioration over the past 2 weeks, and expected survival time ≥ 3 months.
• Women of child-bearing potential (WOCBP) and male patients should agree to take medically acceptable contraception measures while on study treatment and for 3 months following completion of study treatment. All WOCBP must have a negative pregnancy test at screening.
• Patients with measurable CNS lesions must have at least one site of CNS lesion, which has not been previously irradiated, can be accurately measured at baseline as ≥ 10 mm in the longest diameter by MRI, and is suitable for accurate repeated measurements. Measurable extracranial lesions are not required. Patients with non-measurable CNS lesions must have at least one extracranial lesion, which has not been previously irradiated, can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except for lymph nodes which must have a short diameter ≥ 15 mm) by CT/MRI, and is suitable for accurate repeated measurements.
• Prior treatment with EGFR-TKIs (if EGFR-TKIs were used as adjuvant therapy, patients may be enrolled if the time from discontinuation to relapse meets the following requirements: \>6 months for Cohort A, and \>3 months for Cohorts B and C).
• Positive for T790M mutation documented by central or local laboratory using an approved or validated test method, or documented positive KRAS or cMET.
• Patients who have received any investigational drug, biological therapy, or immunotherapy for their malignant tumors within the past 21 days.
• Patients who have had a major surgical procedure (excluding the need for placement of vascular access or a CNS shunt), or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study.
• Presence of only leptomeningeal metastases (LM) disease confirmed by MRI and/or positive cerebrospinal fluid (CSF) pathology, with no brain metastases (BM).
• Prior radiation therapy for CNS metastases that involves measurable or non-measurable sites of disease to assess efficacy.

Sponsors & Collaborators

• Alpha Biopharma (Jiangsu) Co., Ltd.: lead

Study Sites (34)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230000, China

NOT YET RECRUITING

Beijing Tumor Hospital

Beijing, Beijing Municipality, 100000, China

NOT YET RECRUITING

Capital Medical University Affiliated Beijing Chest Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

Chongqing University Affiliated Cancer Hospital

Chongqing, Chongqing Municipality, 404100, China

NOT YET RECRUITING

People's Liberation Army Army Specialized Medical Center

Chongqing, Chongqing Municipality, 404100, China

NOT YET RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350000, China

NOT YET RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 350000, China

NOT YET RECRUITING

Foshan First People's Hospital

Foshan, Guangdong, 510000, China

RECRUITING

Heyou Hospital, Shunde District, Foshan City

Foshan, Guangdong, 528000, China

NOT YET RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

Meizhou People's Hospital

Meizhou, Guangdong, 510000, China

RECRUITING

Affiliated Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

NOT YET RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

NOT YET RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhenzhou, Henan, 450000, China

NOT YET RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

NOT YET RECRUITING

Xiangya Hospital, Central South University

Changsha, Hunan, 41000, China

NOT YET RECRUITING

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, 210000, China

NOT YET RECRUITING

Nanjing Chest Hospital

Nanjing, Jiangsu, 210000, China

NOT YET RECRUITING

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, 225000, China

NOT YET RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

NOT YET RECRUITING

First Hospital of Jilin University

Changchun, Jilin, 130000, China

NOT YET RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, 110000, China

NOT YET RECRUITING

Dalian University of Technology Affiliated Central Hospital (Dalian Central Hospital)

Dalian, Shandong, 116000, China

NOT YET RECRUITING

Qingdao University Affiliated Hospital

Qingdao, Shandong, 266000, China

NOT YET RECRUITING

Shanxi Bethune Hospital

Taiyuan, Shanxi, 030000, China

NOT YET RECRUITING

Shenzhen Hospital, Cancer Hospital, Chinese Academy of Medical Sciences

Shenzhen, Shenzhen, 518000, China

NOT YET RECRUITING

Shenzhen Third People's Hospital

Shenzhen, Shenzhen, 518000, China

NOT YET RECRUITING

Chengdu Third People's Hospital

Chengdu, Sichuan, 610000, China

NOT YET RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuan, 610000, China

NOT YET RECRUITING

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, 30000, China

NOT YET RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650000, China

NOT YET RECRUITING

Yunnan Provincial First People's Hospital

Kunming, Yunnan, 650000, China

NOT YET RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yilong Wu M.D.

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Ge M.D.

CONTACT

+86 (0)21-63862197; john.ge@alphabiopharma.com.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: August 27, 2025
• Study Start: December 29, 2025
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): November 1, 2031
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

CN (34)