ALK Positive Non-small Cell Lung Cancer
Conditions
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.
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.
Interventions
DRUGLorlatinib
lorlatinib 100 mg orally once daily (QD)
DRUGsacituzumab tirumotecan plus lorlatinib
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
Sponsors
Guangdong Association of Clinical Trials
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥ 18 years at the time of signing the informed consent, regardless of gender; 2. 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; 3. 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; 4. Confirmation of ALK fusion by tumor histology, cytology, or blood-based testing; 5. 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; 6. ECOG performance status score of 0 or 1 within 7 days prior to the first dose of study drug; 7. Estimated survival of ≥ 12 weeks; 8. 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.
Exclusion criteria
1. Histological or cytological confirmation of mixed small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma components; 2. 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; 3. Presence of factors affecting oral drug administration; 4. Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of corneal disease that precludes or delays corneal healing; 5. 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; 6. Presence of active central nervous system (CNS) metastases. Subjects with stable asymptomatic CNS metastases may be enrolled; 7. 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); 8. Presence of severe cardiovascular or cerebrovascular disease or cardiovascular risk factors; 9. 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; 10. 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); 11. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From date of first dosing to first documented progression or death from any cause, whichever came first, assessed up to 3 years. | 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. |
| ORR | Up to 2 years | 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. |
| DCR | Up to 2 years | 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. |
| TTR | Up to 2 years | 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. |
| DOR | up to 3 years | 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. |
| OS | up to 5 years | Overall survival (OS) is defined as the time from the start of study treatment to death from any cause. |
Countries
China
Contacts
CONTACTBingfei Xu, MD
PRINCIPAL_INVESTIGATORYi-Long Wu, MD
Guangdong Provincial People's Hospital
Outcome results
None listed