A Study of Lorlatinib in ALK Inhibitor-Treated ALK-Positive NSCLC in China

NCT03909971 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: B7461024NCT03909971
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 21

Brief Summary

A Phase 2, multi center, open label, dual cohort study to evaluate the efficacy and safety of lorlatinib (PF 06463922) monotherapy in ALK inhibitor treated locally advanced or metastatic ALK positive non small cell lung cancer patients in China

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

ALK positive; ALK inhibitor-treated; NSCLC

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Objective Response (Cohort 1)

  Objective response rate (ORR) was defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 relative to the total participants in the analysis population. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as a greater than equal to (\>=) 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Independent Central Radiology (ICR) was used for disease progression assessment.

  From Cycle 1 Day 1 to documented progression of disease by ICR (up to 67 weeks)

Secondary Outcomes (26)

• Percentage of Participants With Objective Response (Cohort 2)

  From Cycle 1 Day 1 to documented progression of disease by ICR (up to 67 weeks)

• Progression-Free Survival (PFS) Based on ICR Assessment

  From first dose (Cycle 1 Day 1) to documented PD by ICR, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure)

• Progression-Free Survival Based on Investigator Assessment

  From first dose (Cycle 1 Day 1) to documented progression of disease by investigator, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure)

• Overall Survival

  From first dose (Cycle 1 Day 1) to date of death due to any cause (up to 271 weeks of treatment exposure)

• Percentage of Participants With Intracranial Objective Response (IC-OR) Based on ICR Assessment

  From first dose (Cycle 1 Day 1) to documented PD by ICR (up to 271 weeks of treatment exposure)

Other Outcomes (1)

• Percentage of Participants With Objective Response (Cohort 1)-Final Analysis

  From first dose (Cycle 1 Day 1) to documented disease progression by ICR (up to 271 weeks of treatment exposure)

Study Arms (1)

Lorlatinib

EXPERIMENTAL

Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

ALK inhibitor-treated ALK-positive NSCL treatment

Also known as: PF-06463922

Lorlatinib

Eligibility Criteria

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

You may qualify if:

• Evidence of histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK positive NSCLC where ALK status has been previously established by the Ventana ALK (D5F3) CDx Assay (Roche Diagnostics), the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular), or the EML4 ALK Fusion Gene Detection Kit (AmoyDx).
• Subject should have:
• (in Cohort 1) Disease progression after crizotinib as the only ALK inhibitor;
• (in Cohort 2) Disease progression after one ALK inhibitor other than crizotinib, with or without prior crizotinib.
• Prior treatment with an ALK inhibitor must have completed 5 half lives prior to study entry.
• All Subjects must have at least 1 measurable extracranial target lesion according to RECIST v1.1 that has not been previously irradiated. CNS metastases are allowed if:
• Asymptomatic: either not currently requiring corticosteroid treatment, or on a stable or decreasing dose of 10 mg QD prednisone or equivalent; or
• Previously diagnosed and treatment has been completed with full recovery from the acute effects of radiation therapy or surgery prior to enrollment, and if corticosteroid treatment for these metastases has been withdrawn for at least 4 weeks with neurological stability.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0, 1, or 2.
• Age 18 years (or 20 years as required by local regulation).
• Adequate bone marrow functions:
• 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:

You may not qualify if:

• Subjects with any of the following characteristics/conditions will not be included in the study:
• More than 1 prior chemotherapy regimen prior to enrollment in advanced/metastatic setting.
• If disease recurred/relapsed within the adjuvant chemotherapy treatment or \<=6 months after the completion of the adjuvant chemotherapy, then the adjuvant chemotherapy is considered as the first line systemic chemotherapy to the disease.
• Systemic anti cancer therapy completed within a minimum of 5 half lives of study enrollment.
• Prior therapy with an antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways, including, but not limited to, anti programmed cell death protein 1 (anti PD 1), anti programmed cell death protein ligand 1 (anti PD L1), anti PD L2, anti cluster of differentiation 137 (anti CD137), or anti cytotoxic T lymphocyte associated antigen 4 (anti CTLA 4) antibody.
• Known epidermal growth factor receptor (EGFR) activating mutations; known prior therapy with EGFR TKI(s) (the prior treatment with brigatinib is allowed as an ALK TKI).
• Major surgery within 4 weeks prior to enrollment. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
• Radiation therapy within 2 weeks prior to enrollment. Palliative radiation must have been completed at least 48 hours prior to enrollment. Stereotactic or partial brain irradiation must have completed at least 2 weeks prior to enrollment. Whole brain irradiation must have completed at least 4 weeks prior to enrollment.
• Spinal cord compression unless the subject has good pain control attained through therapy, and there is complete recovery of neurological function for the 4 weeks prior to enrollment.
• 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 lorlatinib or any component in the formulation; known prior therapy with lorlatinib.
• Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
• Clinically significant cardiovascular disease (both arterial and venous) and non vascular cardiac conditions, (active or within 3 months prior to enrollment, which may include, but not are 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;

Sponsors & Collaborators

• Pfizer: lead

Study Sites (21)

Gaoxin Hospital of The First Affilated Hospital of Anhui Medical University

Hefei, Anhui, 230088, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Fujian Province Oncology Hospital

Fuzhou, Fujian, 350014, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

Location

Hunan Provincial Tumor Hospital/Division of Oncology

Changsha, Hunan, 410013, China

Location

The first hospital of jilin university

Changchun, Jilin, 130021, China

Location

Jilin Provincial Cancer Hospital

Changchun, Jilin, 130103, China

Location

Tangdu Hospital of Fourth Military Medical University

Xi’an, Shanxi, 710000, China

Location

Sichuan Province Cancer Hospital/Department of Pulmonary Tumor

Chengdu, Sichuan, 610041, China

Location

West China Hospital, Sichuan University, Cancer center

Chengdu, Sichuan, 610041, China

Location

The Second Affiliated Hospital of Zhejiang University College of Medicine

Hangzhou, Zhejiang, 310009, China

Location

Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University, Center for Oncology

Hangzhou, Zhejiang, 310016, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Fifth Medical Center of PLA General Hospital

Beijing, 100071, China

Location

Beijing Chest Hospital, Capital Medical University

Beijing, 101149, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 510000, China

Location

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, 310003, China

Location

General Hospital of Eastern Theater Command

Nanjing, China

Location

Shanghai Chest Hospital

Shanghai, 200030, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Zhongshan Hospital, Fudan University

Shanghai, 200032, China

Location

Related Publications (2)

• Lu S, Zhou Q, Liu X, Du Y, Fan Y, Cheng Y, He S, Zhao H, Li H, Wu YL. Updated Efficacy and Safety of Lorlatinib in a Phase 2 Study in Chinese Patients With Previously Treated Advanced ALK-Positive Non-small Cell Lung Cancer. Clin Lung Cancer. 2024 Nov;25(7):e295-e303.e4. doi: 10.1016/j.cllc.2024.04.017. Epub 2024 Apr 30.

  PMID: 38879393 DERIVED

• Niu R, Zhang Y, Pang J, Zhou Q, Lei Y, Du Y. Effective treatment of advanced lung adenocarcinoma with paraneoplastic leukemoid reaction with Lorlatinib: a case report. Front Oncol. 2024 Jan 26;14:1341233. doi: 10.3389/fonc.2024.1341233. eCollection 2024.

  PMID: 38344203 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

lorlatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: April 10, 2019
• Study Start: April 28, 2019
• Primary Completion: August 10, 2020
• Study Completion: October 21, 2024
• Last Updated: November 5, 2025
• Results First Posted: October 26, 2021

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (21)