Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

NCT05740943 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: LORIN
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

A prospective, single-arm, open-label phase 2 study that evaluates the efficacy and safety of induction Lorlatinib in stage III non-small cell lung cancer and explores the clinical feasibility of dynamic ctDNA and multidisciplinary assessment in guiding local treatments.

Conditions

Stage III NSCLC; Surgery

Keywords

ALK fusion; Induction Treatment; Multidisciplinary; ctDNA; Lorlatinib

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  The pathological complete response is defined as the absence of residual tumor in both lung and regional lymph nodes after induction treatment and radical surgery.

  After surgery (approximately 2 weeks)

Secondary Outcomes (6)

• Progression-free Survival (PFS)

  From date of induction treatment till the date of first documented disease progression or death, whichever came first, assessed up to 48 months

• Objective Response Rate (ORR)

  After last dose of induction treatment (approximately 1 week)

• Event-free Survival (EFS)

  From date of radical surgery till the date of first documented disease relapse, assessed up to 48 months

• Dynamic ctDNA alteration

  From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years)

• Overall Survival (OS)

  From date of induction treatment till the date of death from any cause, assessed up to 60 months.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients will receive 12-week induction Lorlatinib followed by radical surgery or local radiotherapy or continue Lorlatinib through MDT and optional consolidation lorlatinib for up to 2 years.

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

Patients were assigned to receive oral lorlatinib at a dose of 100 mg daily in a course of treatment that was measured in cycles of 28 days. 3 cycles of induction treatment will be required for the study.

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age :18 Years to 75 Years;
• ECOG physical score 0-2 points; expected survival time ≥ 1 year;
• Pathologically confirmed diagnosis with Stage III NSCLC which harbored ALK fusion detected by next generation sequencing (NGS) or immunohistochemistry (IHC) with or without FISH. Suspected N2 (station 2/4/7) for stage III disease should be confirmed by either mediastinoscopy or EBUS.
• At least one measurable target lesion according to the RECIST 1.1 standard;
• The main organ function meets the following criteria: 1) blood routine: absolute value of neutrophils ≥ 1.5 × 109 / L, platelets ≥ 75 × 109 / L, hemoglobin ≥ 80 g / L; 2) blood biochemistry: total bilirubin ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal value (if liver metastasis, ≤ upper limit of normal value 5 times), serum creatinine ≤ 1.5 times the upper limit of normal;
• Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.

You may not qualify if:

• Stage I, stage II and metastatic stage IV NSCLC;
• Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
• Patients who have previously used any other anti-tumor drugs or received surgery/radiotherapy;
• Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections.
• Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
• Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
• Patients with low compliance or willingness to take the drugs and surveillance.

Sponsors & Collaborators

• Peking Union Medical College Hospital: collaborator
• Second Xiangya Hospital of Central South University: collaborator
• Guangdong Provincial People's Hospital: lead
• Guangzhou No.12 People's Hospital: collaborator

Study Sites (4)

Peking Union Medical College Hospital

Beijin, Beijin, 100730, China

Location

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

Location

Guangzhou Twelfth People's Hospital

Guangzhou, Guangdong, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

Related Publications (5)

• Zhang C, Li SL, Nie Q, Dong S, Shao Y, Yang XN, Wu YL, Yang Y, Zhong WZ. Neoadjuvant Crizotinib in Resectable Locally Advanced Non-Small Cell Lung Cancer with ALK Rearrangement. J Thorac Oncol. 2019 Apr;14(4):726-731. doi: 10.1016/j.jtho.2018.10.161. Epub 2018 Nov 5.

  PMID: 30408570 BACKGROUND

• Leonetti A, Minari R, Boni L, Gnetti L, Verze M, Ventura L, Musini L, Tognetto M, Tiseo M. Phase II, Open-label, Single-arm, Multicenter Study to Assess the Activity and Safety of Alectinib as Neoadjuvant Treatment in Surgically Resectable Stage III ALK-positive NSCLC: ALNEO Trial. Clin Lung Cancer. 2021 Sep;22(5):473-477. doi: 10.1016/j.cllc.2021.02.014. Epub 2021 Feb 24.

  PMID: 33762169 BACKGROUND

• Zhang C, Yan LX, Jiang BY, Wu YL, Zhong WZ. Feasibility and Safety of Neoadjuvant Alectinib in a Patient With ALK-Positive Locally Advanced NSCLC. J Thorac Oncol. 2020 Jun;15(6):e95-e99. doi: 10.1016/j.jtho.2019.12.133. No abstract available.

  PMID: 32471573 BACKGROUND

• Chaft JE, Dagogo-Jack I, Santini FC, Eng J, Yeap BY, Izar B, Chin E, Jones DR, Kris MG, Shaw AT, Gainor JF. Clinical outcomes of patients with resected, early-stage ALK-positive lung cancer. Lung Cancer. 2018 Aug;122:67-71. doi: 10.1016/j.lungcan.2018.05.020. Epub 2018 May 22.

  PMID: 30032847 BACKGROUND

• Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. doi: 10.1056/NEJMoa2027187.

  PMID: 33207094 BACKGROUND

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

Study Officials

• Wen-Zhao Zhong, MD.

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

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: Head of Pulmonary Surgery

Model Details: A Simon two-stage design was applied. Primary endpoint for this study was pCR. The unacceptable response rate for pCR was less than 20% and desirable response rate was 40%. The error rate for alpha was set as 0.05 and 0.2 for beta. The Optimal assay was chosen and 43 patients were to be enrolled to meet adequate statical power. 13 patients would be enrolled in stage I and at least 3 patients achieved pCR were required to proceed stage II enrollment. Overall, if 12 patients achieved pCR, the study would be determined as positive. 10% drop-off rate should be considered and at least 48 patients should be enrolled.

Study Record Dates

• First Submitted: February 12, 2023
• First Posted: February 23, 2023
• Study Start: March 15, 2023
• Primary Completion: December 31, 2025
• Study Completion: April 30, 2026
• Last Updated: January 20, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)