ALK Positive Non-small Cell Lung CancerPhase 2NCT07750704
Lorlatinib Plus Sacituzumab Tirumotecan With Peripheral ctDNA Guidance as First-Line Therapy for ALK Fusion-Positive NSCLC
A Phase 2 study testing Lorlatinib and sacituzumab tirumotecan plus lorlatinib in people with ALK Positive Non-small Cell Lung Cancer, run by Guangdong Association of Clinical Trials at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALK Positive Non-small Cell Lung Cancer
- What is being tested?
- Lorlatinib and sacituzumab tirumotecan plus lorlatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 1 siteChina
- Study dates
- Sep 2026to Mar 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
- Patients must have at least one measurable lesion according to RECIST v1.1. Lesions that have been previously irradiated should not be selected as target lesions. Subjects with only skin lesions or bone lesions are not eligible for inclusion;
- 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.
Who cannot join
- 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;
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- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Guangdong Provincial Perople's Hospital
Guangzhou, Guangdong
Bingfei Xu, MD, 13036100430, xubingfei@gdph.org.cn
Yi-Long Wu, MD
About this study
Official title: Lorlatinib Combined With Sacituzumab Tirumotecan Based on Peripheral Blood ctDNA as First-Line Treatment for Patients With ALK Fusion-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Prospective, Open-Label, Multicenter Study
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.
Read the detailed description
All enrolled subjects are patients with locally advanced or metastatic ALK fusion NSCLC who are not candidates for curative therapy. This study plans to enroll approximately 153 eligible subjects, who will be stratified into a ctDNA-positive group and a ctDNA-negative group based on baseline peripheral blood ctDNA status. Subjects in the ctDNA-negative group will receive lorlatinib monotherapy. Subjects in the ctDNA-positive group will be randomized in a 1:1 ratio to receive either lorlatinib combined with sacituzumab tirumotecan or lorlatinib monotherapy. Each treatment cycle consists of 4 weeks (28 days). Subjects receiving lorlatinib monotherapy will receive lorlatinib 100 mg orally once daily (QD). Subjects receiving the combination therapy will receive 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.
- Conditions
- ALK Positive Non-small Cell Lung Cancer
- Being tested
- Lorlatinib, sacituzumab tirumotecan plus lorlatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LorlatinibDrug
lorlatinib 100 mg orally once daily (QD)
sacituzumab tirumotecan plus lorlatinibDrug
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
| Study group | Role | What they receive |
|---|---|---|
| baseline ctDNA negative | Active comparator | Not described Receives: Drug: Lorlatinib |
| baseline ctDNA positive-lorlatinib | Experimental | Not described Receives: Drug: Lorlatinib |
| baseline ctDNA positive-lorlatinib+sacituzumab tirumotecan | Experimental | Not described Receives: Drug: sacituzumab tirumotecan plus lorlatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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.
Measured: From date of first dosing to first documented progression or death from any cause, whichever came first, assessed up to 3 years.
ORR
The objective response rate (ORR) is defined as the proportion of subjects in the analysis population who achieve a complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST version 1.1 criteria.
Measured: Up to 2 years
DCR
The disease control rate (DCR) is defined as the proportion of subjects who achieve complete response (CR), partial response (PR), or stable disease (SD) as assessed by the investigator according to RECIST version 1.1 criteria.
Measured: Up to 2 years
TTR
Time to response (TTR) is defined as the interval from the first dose to the first documented complete response (CR) or partial response (PR), as assessed by the investigator according to RECIST version 1.1 criteria.
Measured: Up to 2 years
DOR
Duration of response (DOR) is defined as the time interval from the first documented response to disease progression or death (whichever occurs first), as assessed by the investigator according to RECIST version 1.1 criteria.
Measured: up to 3 years
OS
Overall survival (OS) is defined as the time from the start of study treatment to death from any cause.
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2029 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALK Positive Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 153 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Association of Clinical Trials
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yi-Long Wu, Guangdong Association of Clinical Trials
- Investigators
- Yi-Long Wu, MD, Principal investigator, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07750704
- Sponsor's protocol ID
- CTONG2602
- Status last verified
- Aug 2026
- First submitted
- 2 Aug 2026
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No