Lorlatinib Plus Sacituzumab Tirumotecan With Peripheral ctDNA Guidance as First-Line Therapy for ALK Fusion-Positive NSCLC

NCT07750704 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: CTONG2602
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 1

Brief Summary

This investigator-initiated, open-label, prospective Phase II clinical trial, planned to take place across multiple centers in China. We design this trial to evaluate the safety and efficacy of lorlatinib plus sacituzumab tirumotecan based on peripheral blood ctDNA as first-line treatment for ALK fusion NSCLC.

Conditions

ALK Positive Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 1-year PFS rate

  PFS is defined as the time from the start of study treatment to the first documented radiographic disease progression or death from any cause, whichever occurs first (according to RECIST v1.1). The Kaplan-Meier method will be used to estimate the median PFS and its 95% confidence interval, to generate survival curves, and to calculate the 1-year PFS rate

  From date of first dosing to first documented progression or death from any cause, whichever came first, assessed up to 1 year.

Secondary Outcomes (6)

• PFS

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

• ORR

  Up to 2 years

• DCR

  Up to 2 years

• TTR

  Up to 2 years

• DOR

  up to 3 years

Study Arms (3)

baseline ctDNA negative

ACTIVE COMPARATOR

Drug: Lorlatinib

baseline ctDNA positive-lorlatinib

EXPERIMENTAL

Drug: Lorlatinib

baseline ctDNA positive-lorlatinib+sacituzumab tirumotecan

EXPERIMENTAL

Drug: sacituzumab tirumotecan plus lorlatinib

Interventions

Lorlatinib DRUG

lorlatinib 100 mg orally once daily (QD)

baseline ctDNA negative; baseline ctDNA positive-lorlatinib

sacituzumab tirumotecan plus lorlatinib DRUG

lorlatinib 100 mg orally once daily (QD) plus sacituzumab tirumotecan 4 mg/kg administered as an intravenous infusion on Day 1 and Day 15 of each 4-week cycle (Q4W) for 4 cycles

baseline ctDNA positive-lorlatinib+sacituzumab tirumotecan

Eligibility Criteria

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

You may qualify if:

• Patients aged ≥ 18 years at the time of signing the informed consent, regardless of gender;
• Histologically/cytologically confirmed NSCLC, Stage III (locally advanced) or IV (metastatic), unsuitable for curative surgery and/or curative radiotherapy, with or without prior concurrent/sequential chemotherapy;
• No prior systemic therapy for locally advanced or metastatic NSCLC, patients previously treated with curative-intent adjuvant/neoadjuvant chemo or concurrent/sequential chemoradiotherapy for non-metastatic disease are eligible if progression occurred ≥ 12 months after the last treatment;
• Confirmation of ALK fusion by tumor histology, cytology, or blood-based testing;
• ECOG performance status score of 0 or 1 within 7 days prior to the first dose of study drug;
• Estimated survival of ≥ 12 weeks;
• Adequate organ and bone marrow function, without having received blood transfusion, recombinant human thrombopoietin, or colony-stimulating factors within 2 weeks prior to the first dose of study drug.

You may not qualify if:

• Histological or cytological confirmation of mixed small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma components;
• Prior receipt of any of the following therapies (including in the adjuvant or neoadjuvant setting): a) TROP2-targeted therapy; b) Any therapy containing topoisomerase I, including antibody-drug conjugate (ADC) therapy; c) Lorlatinib targeted therapy;
• Presence of factors affecting oral drug administration;
• Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of corneal disease that precludes or delays corneal healing;
• Presence of spinal cord compression. Subjects who have received adequate local treatment (surgery or radiotherapy) and have clinical evidence of symptom relief for ≥ 1 week prior to the first dose may be enrolled;
• Presence of active central nervous system (CNS) metastases. Subjects with stable asymptomatic CNS metastases may be enrolled;
• Presence of other malignancy within 3 years prior to the first dose (except for tumors cured by local therapy or in situ carcinomas that do not require immediate treatment);
• Presence of severe cardiovascular or cerebrovascular disease or cardiovascular risk factors;
• History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid therapy, current ILD or non-infectious pneumonitis, or suspected ILD or non-infectious pneumonitis that cannot be ruled out by imaging at screening;
• Prior antitumor therapy-related toxicities have not recovered to ≤ grade 1 (based on NCI CTCAE v5.0) or to the levels specified in the eligibility criteria (excluding toxicities deemed by the investigator to be of low safety risk, such as alopecia, fatigue, or peripheral neuropathy);
• Active hepatitis B (hepatitis B surface antigen \[HBsAg\] positive, requiring HBV-DNA testing; HBV-DNA ≥ 2000 IU/mL or above the lower limit of detection, whichever is higher) or hepatitis C (positive for hepatitis C antibody with HCV-RNA above the lower limit of detection).

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (1)

Guangdong Provincial Perople's Hospital

Guangzhou, Guangdong, China

Location

MeSH Terms

Interventions

lorlatinib

Study Officials

• Yi-Long Wu, MD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bingfei Xu, MD

CONTACT

13036100430; xubingfei@gdph.org.cn

Study Design

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

Study Record Dates

• First Submitted: August 2, 2026
• First Posted: August 6, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): March 1, 2030
• Last Updated: August 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)