Real-world Study of Local Therapy Changes During 1L Lorlatinib in Unresectable ALK+ NSCLC (COMLORLA)

A Real-world Study to Explore Therapeutic Changing Mode of Locally Therapy During 1L Lorlatinib Treatment in Unresectable ALK+ NSCLC Patients

This real-word study is designed to prospectively explore whether local treatment (surgery, ablation, radiotherapy and others) can prolong the time to treatment discontinuation during 1L lorlatinib treatment in Chinese patients with unresectable ALK+ NSCLC. Participation in this study is not intended to change the routine treatment received as determined by their attending physicians. Patients will be treated according to the routine medical practice in terms of visit frequency and types of assessments performed.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Cancer, Non-Small Cell
• Intervention / Treatment: Drug: Lorlatinib 100 mg

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Jun Zhao; Phone Number: 86（010）88196456; Email: ohjerry@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

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).

Description

1 Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

1.1. Diagnosis:

1. 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).
2. Tumor Requirements: At least 1 measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. Brain metastases are allowed.

1.2. No prior systemic treatment for advanced (Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) disease.

1.3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, 2 or 3.

1.4. Age ≥18 years. 1.5. Adequate Liver Function, including:

1. Total serum bilirubin ≤1.5 x ULN;
2. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN (≤5.0 x ULN in case of liver metastases).

1.6. Life expectancy at least 6 months. 1.7. Serum pregnancy test (for females of childbearing potential) negative at screening. Female patients of non-childbearing potential must meet at least 1 of the following criteria:

1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause (which may be confirmed with a serum follicle-stimulating hormone [FSH] level confirming the postmenopausal state if appropriate);
2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
3. Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential. 1.8. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

1.9. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures. 2.Exclusion Criteria

Subjects presenting with any of the following characteristics/conditions will not be included in this clinical study:

2.1. 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.

2.2. Radiation therapy within 2 weeks prior to enrollment, 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.

2.3. 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.

2.4. Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations.

2.5. 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.

2.6. 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.

2.7. Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug fall into any of the above categories) within 12 days prior to the first dose of lorlatinib.

1. Known strong CYP3A inhibitors (e.g., strong CYP3A inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville oranges, pomelos], boceprevir, cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, ritonavir alone and with danoprevir or elvitegravir or indinavir or lopinavir or paritaprevir or ombitasvir or dasabuvir or saquinavir or tipranavir, telaprevir, troleandomycin, and voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
2. Known CYP3A substrates with narrow therapeutic index, such as astemizole*, terfenadine*, cisapride*, pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine) (*withdrawn from US market).
3. Known strong CYP3A inducers (e.g., carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's Wort). d. Known P-gp substrates with a narrow therapeutic index (e.g., digoxin).

2.8. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

2.9. Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to treatment discontinuation (TTD)	Time-to treatment discontinuation is defined as the time from start of treatment to the date of discontinuation of these therapeutic methods.	From November 2024 to April 2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	proportion of patients with a Complete Response (CR) or Partial Response (PR) as a best response during the lorlatinib treatment. Responses to treatment will be defined according to investigator	From November 2024 to April 2027
Duration of response (DOR)	time between the first documentation of objective response and the first documentation of disease progression or death from any cause whichever occurred first, for participants with a confirmed objective response of CR or PR.	From November 2024 to April 2027
Time to Progression (TTP)	Based on Investigator's Assessment	From November 2024 to April 2027
Intracranial Objective Response Rate (IC-ORR)	proportion of patients with intracranial objective response of complete response (CR) or partial response (PR) as a best response in the subset of patients with at least 1 intracranial lesion assessed by investigator.	From November 2024 to April 2027
Intracranial Time to Progression (IC-TTP)	Time from inclusion to the date of the first documentation of disease progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases.	From November 2024 to April 2027
Overall Survival (OS)	Time from inclusion to date of death from any cause.	From November 2024 to April 2027
Safety: To explore the adverse events (AEs), the dose modification and the reason for interruption or discontinuation of lorlatinib in first line for Chinese patients with ALK-positive locally advanced or metastatic NSCLC recorded in medical records		From November 2024 to April 2027
Proportion of patients experiencing a 10-points change from baseline in total score for the EORTC QLQ-C30	evaluate Health-related Quality of life (HRQoL) of ALK- positive locally advanced or metastatic NSCLC patients treated with lorlatinib in first-line using the EORTC QLQ-C30 questionnaires	From November 2024 to April 2027
Dynamic molecular response	Mutational Analysis; measured by next-generation sequencing (NGS) if available in real world setting;	From November 2024 to April 2027
Safety and tolerability of the therapeutic changing mode	Safety profile according to CTCAE v.5	From November 2024 to April 2027

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamic ctDNA change during lorlatinib treatment	Plasma samples collected at several timepoints, analyzed by next-generation sequencing	From November 2024 to April 2027
Biomarkers of sensitivity or resistance to lorlatinib in no-prior ALK-TKIs treatment tumor tissue and peripheral blood if available in real world setting		From November 2024 to April 2027

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): November 10, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): October 31, 2030

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 2024YJZ112

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes