Lorlatinib as the First-line Treatment in China Advanced ALK+ NSCLC

NCT06092086 | Recruiting Phase 2

• 1 other identifier: CTONG2203
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II study is aim to investigate the efficacy, resistance mechanism, safety profile of first-line lorlatinib in China advanced ALK+ non-small cell lung cancer (NSCLC). Participants will receive continuous daily PO dosing of lorlatinib 100mg QD.

Conditions

ALK Positive Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• PFS

  Progression Free Survival (PFS) is defined as the time from start of lorlatinib treatment to the date of disease progression as defined by RECIST v1.1 per investigator review or death due to any cause, whichever occurred first.

  From date of first dosing to first documented progression or death from any cause, whichever came first, assessed up to 3 years.

• Resistance mechanism of lorlatinib

  Resistance mechanism of first-line lorlatinib treatment by tumor tissue, and peripheral blood ctDNA (circulating tumor Deoxyribonucleic acid) biomarkers including, but not limited to, ALK gene rearrangement and/or ALK kinase domain mutations as measured by next-generation sequencing (NGS);

  From date of first dosing to first documented progression or death from any cause, whichever came first, assessed up to 3 years.

Study Arms (1)

CROWN Criteria (CC) Cohort、Compassionate use (CU) Cohort

EXPERIMENTAL

Drug: Loratinib

Interventions

Loratinib DRUG

Continuous daily PO dosing of lorlatinib 100mg QD.

Also known as: LORBRENA

CROWN Criteria (CC) Cohort、Compassionate use (CU) Cohort

Eligibility Criteria

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

You may qualify if:

• Diagnosis:
• Study Population: Patients with histologically or cytologically confirmed diagnosis of locally advanced \[(Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 7.0\] ALK-positive NSCLC where ALK status is determined by the Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT Platforms, FISH, PCR, or next generation sequencing (NGS), or circulating tumor DNA (ctDNA).
• Tumor Requirements: At least 1 extracranial measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. CNS metastases are allowed if asymptomatic and:
• Either untreated and not currently requiring corticosteroid treatment, or on a stable or decreasing dose of ≤10 mg QD prednisone or equivalent; or
• Local treatment has been completed with full recovery from the acute effects of radiation therapy or surgery prior to randomization, and if corticosteroid treatment for these metastases has been withdrawn for at least 4 weeks with neurological stability; or
• In case of leptomeningeal disease (LMD) or carcinomatous meningitis (CM) if visualized on magnetic resonance imaging (MRI), or if baseline CSF positive cytology is available.
• Tissue Requirements: All patients must have an archival formalin fixed, paraffin embedded (FFPE) tissue specimen available and collected prior to randomization. If archived tissue is unavailable, then a mandatory de novo biopsy must be performed.
• No prior systemic NSCLC treatment for advanced (Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) disease, including molecularly targeted agents (e.g., ALK TKIs), angiogenesis inhibitors, immunotherapy, or chemotherapy. Prior treatment for earlier Stages of the NSCLC only allowed if completed more than 12 months prior to randomization.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2.
• Age ≥18 years.
• Adequate Bone Marrow Function, including:
• Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 or ≥1.5 x 109/L;
• Platelets ≥100,000/mm3 or ≥100 x 109/L;
• Hemoglobin ≥9 g/dL.
• Adequate Pancreatic Function, including:

You may not qualify if:

• Subjects presenting with any of the following characteristics/conditions will not be included in this clinical study:
• Spinal cord compression unless the patient has good pain control attained through therapy, and there is stabilization or recovery of neurological function for the 4 weeks prior to randomization.
• Major surgery within 4 weeks prior to randomization. Minor surgical procedures (e.g., port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
• Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Patients who complete whole brain irradiation within 4 weeks prior to randomization or palliative radiation therapy outside of the CNS within 48 hours prior to randomization will also not be included in the study.
• Gastrointestinal abnormalities, including inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection or lap band; active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer disease in the past 6 months; malabsorption syndromes.
• Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations.
• Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV) (e.g., in case of known HBsAg or HCV antibody positivity), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness.
• Clinically significant vascular (both arterial and venous) and non-vascular cardiac conditions, (active or within 3 months prior to enrollment), which may include, but are not limited to:
• Arterial disease such as cerebral vascular accident/stroke (including Transient Ischemic Attack -TIA), myocardial infarction, unstable angina;
• Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary embolism;
• Non-vascular cardiac disease such as congestive heart failure (New York Heart Association Classification Class ≥ II), second-degree or third-degree AV block (unless paced) or any AV block with PR \>220 msec; or ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as \<50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read Electrocardiogram (ECG) with QTc \>470 msec, or congenital long QT syndrome.
• Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (e.g., uncontrolled hyperglycemia, current gallstone disease) in the last month prior to randomization.
• History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis.
• Evidence of active malignancy (other than NSCLC, non-melanoma skin cancer, or localized prostate cancer or any in situ cancer which does not currently require treatment) within the last 3 years prior to randomization.
• Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug falls into any of the above categories) within 12 days prior to the first dose of lorlatinib.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (1)

Guangdong Provincial Perople's Hospital

Guangzhou, Guangdong, 023187, China

RECRUITING

Related Publications (1)

• Lin JX, Zhou Q, Yan HH, Liu AW, Wu GW, Chu Q, Du YY, Cui JW, Cheng Y, Yang Y, Xu HP, Tu HY, Wu YL, Liu SM. A Patient-Centric, Open-Label, Multicenter, Phase II Study of Lorlatinib Monotherapy in the First-Line Treatment of Patients With locally Advanced or Metastatic ALK-Positive Non-Small Cell Lung Cancer (CTONG2203). Clin Lung Cancer. 2025 Sep;26(6):515-519. doi: 10.1016/j.cllc.2025.05.014. Epub 2025 May 28.

  PMID: 40541556 DERIVED

MeSH Terms

Interventions

lorlatinib

Study Officials

• Yi-Long Wu, MD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiaxin Lin, PhD

CONTACT

+8618928737479; linjiaxin@gdph.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single drug administration

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: October 23, 2023
• Study Start: August 18, 2023
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2030
• Last Updated: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)