NCT04541706

Lorlatinib in ALK Inhibitor Treated Unresectable Advanced/Recurrent ALK-Positive Non Small Cell Lung Cancer Patients in India

Completed Phase 4 Results posted Last updated 20 December 2024

What this trial tests

Phase 4 trial testing Lorlatinib in Advanced Non-Small Cell Lung Cancer in 100 participants. Completed in 20 July 2022.

Timeline

27 August 2020

Primary endpoint
20 July 2022

20 July 2022

Quick facts

Lead sponsor	Pfizer
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	100
Start date	27 August 2020
Primary completion	20 July 2022
Estimated completion	20 July 2022
Sites	12 locations across India

Drugs / interventions tested

• Lorlatinib (lorlatinib) — full drug profile →

Conditions studied

• Advanced Non-Small Cell Lung Cancer — all drugs for Advanced Non-Small Cell Lung Cancer →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Advanced Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · From Day 1 up to 35 days post last dosing date or the date of initiation of a new anticancer therapy (up to 1.9 years)

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily need to have a causal relationship with the treatment or usage. A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. If the investigator did not know whether or not the investigational product caused the event, then the event would be handled as "related to investigational product" for reporting purposes, as defined by the sponsor. If the

All-causality TEAEs

Group	Value	95% CI
Lorlatinib 100 mg QD	94

Treatment-related TEAEs

Group	Value	95% CI
Lorlatinib 100 mg QD	89

Confirmed Objective Responses Rate (ORR) Based on Investigator Assessment Secondary · Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

ORR was defined as the percentage of participants with best overall response as confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR was provided along with the corresponding 95% confidence interval (CI) based on Wilson's Score Method. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the target lesions.

Group	Value	95% CI
Lorlatinib 100 mg QD	41	31.9 – 50.8

Confirmed Intracranial Objective Response Rate (IC-ORR) Based on Investigator Assessment Secondary · Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

IC-ORR was defined as the percentage of participants with intracranial response (ie, best overall intracranial response as confirmed CR or confirmed PR considering only intracranial lesions) relative to participants with central nervous system (CNS) metastases at study entry. IC-ORR was provided along with the corresponding 95% CI based on Wilson's Score Method. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the target lesions.

Group	Value	95% CI
Lorlatinib 100 mg QD	35.7	24.5 – 48.8

Duration of Response (DoR) Secondary · Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

DoR was defined as the time from the first documentation of objective tumor response (confirmed CR or confirmed PR) to the first documentation of disease progression or death due to any cause, whichever occurred first. For participants whose responses proceed from PR to CR, the onset of PR was taken as the onset of response. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the target lesions.

Group	Value	95% CI
Lorlatinib 100 mg QD	NA	NA – NA

Intracranial Duration of Response (IC-DoR) Secondary · Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

IC-DoR was defined as the time from the first documentation of an intracranial objective response (confirmed CR or confirmed PR) to the first documentation of disease progression or death due to any cause, whichever occurred first in the subgroup of participants with brain metastasis at baseline. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the target lesions.

Group	Value	95% CI
Lorlatinib 100 mg QD	NA	11.1 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From Day 1 up to 35 days post last dosing date or the date of initiation of a new anticancer therapy (up to 1.9 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lorlatinib 100 mg QD

Serious: 22/100 (22%)

Deaths: 8/100

Serious adverse events (23 terms)

Reaction	System	Lorlatinib 100 mg QD
COVID-19	Infections and infestations	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—
Cardiac arrest	Cardiac disorders	—
Cardiac tamponade	Cardiac disorders	—
Cardio-respiratory arrest	Cardiac disorders	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—
Sudden death	General disorders	—
COVID-19 pneumonia	Infections and infestations	—
Lower respiratory tract infection	Infections and infestations	—
Pneumonia aspiration	Infections and infestations	—
Suspected COVID-19	Infections and infestations	—
Transfusion reaction	Injury, poisoning and procedural complications	—
Joint swelling	Musculoskeletal and connective tissue disorders	—
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Altered state of consciousness	Nervous system disorders	—
Cognitive disorder	Nervous system disorders	—
Hypersomnia	Nervous system disorders	—
Seizure	Nervous system disorders	—
Acute psychosis	Psychiatric disorders	—
Mania	Psychiatric disorders	—
Dyspnoea at rest	Respiratory, thoracic and mediastinal disorders	—
Respiratory distress	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (17 terms — click to expand)

Reaction	System	Lorlatinib 100 mg QD
Hypertriglyceridaemia	Metabolism and nutrition disorders	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—
Weight increased	Investigations	—
Oedema peripheral	General disorders	—
Anaemia	Blood and lymphatic system disorders	—
Hyperlipidaemia	Metabolism and nutrition disorders	—
Hyperglycaemia	Metabolism and nutrition disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Hypomagnesaemia	Metabolism and nutrition disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Oedema	General disorders	—
Dyslipidaemia	Metabolism and nutrition disorders	—
Hypertension	Vascular disorders	—
Peripheral swelling	General disorders	—
COVID-19	Infections and infestations	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—

Most-reported serious reactions: COVID-19, Dyspnoea, Acute respiratory distress syndrome, Cardiac arrest, Cardiac tamponade, Cardio-respiratory arrest, Gastrointestinal haemorrhage, Sudden death.

Data from ClinicalTrials.gov NCT04541706 adverse events section.

Sponsor's own description

Lorlatinib is a third-generation, oral, reversible, ATP-competitive, macrocyclic TKI of ALK and ROS1. Lorlatinib was specifically designed to penetrate the CNS and to overcome known secondary resistance mutations in the ALK tyrosine kinase domain.

This is a Phase 4, open-label, multicenter, non-randomized, prospective, single arm study to evaluate the safety and tolerability of lorlatinib in adult participants with unresectable advanced and/or recurrent ALK-positive NSCLC with resistance or intolerance to at least 1 prior ALK inhibitor treatment.

This study is being conducted as a post approval study to fulfill Central Drugs Standard Control Organization (CDSCO) request relating to additional information on use of Lorlatinib in Indian patients.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Update on the Treatment of Non-Small Cell Lung Carcinoma (NSCLC).
   Kariri YA. · · 2025 · PMID 41096039 · DOI 10.3390/jcm14196960
2. Phase IV clinical trials for the treatment of non-small cell lung carcinoma (NSCLC): A systemic review from 2020-2025.
   Kariri YA, Alqasmi MH, Alqahtani BS. · · 2025 · PMID 41087063 · DOI 10.15537/smj.2025.46.10.20250385