Extrapulmonary Neuroendocrine Carcinoma
Conditions
Brief summary
This trial is a Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of QLC5508 versus investigator's choice chemotherapy in participants with advanced EP-NEC that has failed after at least one prior platinum-based chemotherapy regimen.
Interventions
DRUGInvestigator's Choice Chemotherapy (FOLFIRI or FOLFOX regimen)
FOLFIRI regimen: Irinotecan 180 mg/m² intravenous infusion on Day 1 and Day 15, leucovorin 400 mg/m² intravenous infusion on Day 1 and Day 15, and fluorouracil 400 mg/m² intravenous push on Day 1 and Day 15, followed by fluorouracil 2400 mg/m² via continuous intravenous infusion over 46-48 hours, once every 2 weeks. Each treatment cycle is 4 weeks. FOLFOX regimen: oxaliplatin 85 mg/m² intravenous infusion on Day 1 and Day 15, leucovorin 400 mg/m² intravenous infusion on Day 1 and Day 15, and fluorouracil 400 mg/m² intravenous push on Day 1 and Day 15, followed by fluorouracil 2400 mg/m² via continuous intravenous infusion over 46-48 hours, once every 2 weeks. Each treatment cycle is 4 weeks.
DRUGQLC5508
QLC5508 will be administered intravenously once every 2 weeks. Each treatment cycle is 4 weeks.
Sponsors
Qilu Pharmaceutical Co., Ltd.
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. Voluntarily consent to participate in this study and sign the informed consent form. 2. Males and females aged ≥18 years old; 3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1; 4. Estimated survival time of more than 3 months. 5. A serum pregnancy test must be performed within 7 days prior to randomization for premenopausal women of childbearing potential, and the result must be negative and must not be lactating; All enrolled patients and the partners should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment. 6. Capable of understanding trial requirements, willing and able to comply with trial and follow-up procedures. 7. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0 (v6.0). 8. Voluntarily sign the written informed consent form and comply with the protocol requirements. 9. Histologically or cytologically confirmed advanced extrapulmonary neuroendocrine carcinoma (EP-NEC) 10. Has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) as assessed by the investigator. 11. Sufficient bone marrow and organ function.
Exclusion criteria
1. Diagnosis of other primary malignancies within 5 years prior to signing the informed consent form. 2. Patients diagnosed with Merkel cell carcinoma or medullary thyroid carcinoma. 3. Brain metastases (unless asymptomatic and no progression confirmed by imaging ≥4 weeks prior to randomization); Presence of leptomeningeal metastases or brainstem metastases; Spinal cord compression (identified via imaging, regardless of symptoms). 4. Previous or ongoing treatment with topoisomerase I inhibitors 5. Having previously received B7-H3-targeted therapy. 6. Insufficient washout of prior anticancer therapies prior to randomization. 7. Having underwent major organ surgery (excluding biopsy) or significant trauma within 4 weeks prior to randomization; Requiring elective surgery during the study. 8. Having received live vaccine or live attenuated vaccine within 4 weeks before study randomization. 9. Having received treatment with systemic corticosteroids (prednisone at \>10 mg/day, or similar drugs at equivalent dose) or other immunosuppressive agents within 14 days prior to randomization. 10. Moderate to severe pulmonary disease significantly impairing lung function, including idiopathic pulmonary fibrosis, autoimmune/connective tissue disorders with lung involvement, or prior pneumonectomy. 11. Having a history of interstitial lung disease (ILD)/ non-infectious pneumonitis that required corticosteroids, current ILD/ non-infectious pneumonitis, or suspected ILD/ non-infectious pneumonitis that cannot be ruled out by imaging at screening; 12. Active tuberculosis; Autoimmune diseases not in clinical remission, other acquired or congenital immunodeficiency diseases; Having a history of allogeneic stem cell, bone marrow, or organ transplantation. 13. Serious infections (e.g., bacteremia, or severe pneumonia) within 4 weeks prior to randomization; Active infection requiring systemic antibiotic therapy within 1 weeks prior to randomization; 14. Having positive results in virus serology tests (hepatitis B virus infection participants receiving antiviral treatment other than interferon are allowed to be enrolled). 15. Uncontrolled or significant cardiovascular disease. 16. Clinically uncontrolled third-space effusion. 17. Drug abuse. 18. Having alcohol or drug dependence. 19. Poor compliance as per investigator discretion; Any other medical conditions that may interfere with study participation or the results of the clinical study as per the discretion of investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to approximately 48 months | OS is defined as the duration from the date of randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to approximately 48 months | PFS is defined as the duration from the date of randomization to the date of first documented progressive disease (PD) based on investigator assessment, or death from any cause, whichever occurs first. |
| Objective response rate (ORR) | Up to approximately 48 months | ORR is defined as the percentage of participants achieved complete response or partial response as assessed according to RECIST v1.1 criteria. |
| Duration of response (DOR) | Up to approximately 48 months | DOR is defined as the duration from the first documented objective response to the first documented disease progression or death from any cause, whichever occurs first. |
| Disease control rate (DCR) | Up to approximately 48 months | DCR is defined as the percentage of participants achieved complete response, partial response, or stable disease as assessed according to RECIST v1.1 criteria. |
| Treatment Emergent Adverse Event (TEAE) | Up to approximately 48 months | TEAEs are defined as any adverse event (AE) that occurs after the initiation of study treatment, or any pre-existing condition that worsens in severity or frequency after the initiation of study treatment, regardless of the causal relationship to the study treatment. TEAEs will be graded and summarized by type, frequency, and severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 6.0. |
Contacts
CONTACTHong Sun, Bachelor
Outcome results
None listed