DCSZ11, HNSCC, Solid Tumors
Conditions
Brief summary
To evaluate the safety and efficacy of DCSZ11 in combination with standard therapy in patients with advanced or metastatic solid tumors.
Interventions
DRUGLow Dose DCSZ11
Patients will receive DCSZ11 at 600 mg every three weeks (Q3W).
DRUGMedium Dose DCSZ11
Patients will receive DCSZ11 at 800 mg Q3W.
DRUGHigh Dose DCSZ11
Patients will receive DCSZ11 at 1200 mg Q3W.
DRUGStandard Treatment
The available standard treatment for head and neck cancer patients.
Sponsors
West China Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This single-center, open-label, single-arm trial employs a dose-escalation framework to assess DCSZ11's safety and biological activity when co-administered with guideline-directed standard therapy in advanced solid tumor patients. All participants will maintain fixed chemotherapy/immunotherapy regimens specific to their malignancy, with sole dose variation occurring for DCSZ11. Three subjects in the lead-in cohort will initiate DCSZ11 at 600 mg triweekly. Sequential cohorts will escalate to 800 mg and 1200 mg administered Q3W. The 800 mg tier derives from prior clinical evidence (NCT05785754) evaluating DCSZ11-pembrolizumab combinations. Incorporation of the 600 mg cohort facilitates refined escalation protocols and enhanced resolution in safety/tolerability profiling. Dose-limiting toxicities (DLTs) will undergo surveillance through a 21-day monitoring window. Escalation decisions will implement the Bayesian Optimal Interval (BOIN) methodology, with DLT classifications adhering to
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged ≥18 years. 2. Willing and able to provide written informed consent for the study. 3. Patients with histologically confirmed advanced or metastatic solid tumors. Note: Patients must have guideline-eligible standard chemotherapy and immunotherapy options available.Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) must have PD-L1 Combined Positive Score (CPS) ≥1.Lung cancer patients with known actionable driver gene mutations/genomic aberrations (e.g., EGFR sensitizing mutations, BRAF V600E mutation, ROS1 rearrangements, NTRK gene fusions, ALK rearrangements) are excluded.Prior adjuvant or neoadjuvant chemotherapy is permitted, provided ≥6 months have elapsed between the last dose of chemotherapy/immunotherapy and documented recurrent disease.Gastric cancer patients must be HER2-negative. 4. Patients must have at least one measurable lesion per RECIST 1.1 criteria. Lesions located in previously irradiated areas may be considered measurable if there is objective evidence of progression in those lesions prior to study enrollment. 5. Patients with previously treated central nervous system (CNS) metastases are eligible provided they meet all the following criteria: 1. Stability (i.e., no evidence of progression on magnetic resonance imaging \[MRI\]) for ≥4 weeks prior to the first dose of study drug, and 2. All neurological symptoms have returned to baseline, and 3. No requirement for steroid therapy for at least 14 days prior to the first dose of study intervention. Patients with signs or symptoms suggestive of CNS metastases must undergo brain imaging within 2 weeks prior to the first dose of study drug to confirm the absence of detectable CNS disease. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Adequate organ function and bone marrow reserve per laboratory assessments within 10 days prior to first study drug administration: 1. Bone marrow function: * Absolute neutrophil count (ANC) ≥1,500/µL * Hemoglobin ≥9 g/dL (must be achieved without erythropoietin dependency AND without packed red blood cell \[pRBC\] transfusion within the preceding 2 weeks) * Platelet count ≥100,000/µL 2. Hepatic function: * Total serum bilirubin ≤1.5 × upper limit of normal (ULN); or direct bilirubin ≤ULN for patients with total bilirubin \>1.5 × ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN if liver metastases present) 3. Renal function: * Estimated creatinine clearance ≥30 mL/min (per Cockcroft-Gault formula) 8. PD-L1 status must be available for all patients via approved immunohistochemistry assay. 9. Resolution of all prior treatment-related toxicities to Grade ≤1 or baseline, or determination as irreversible sequelae. \*Note: Grade ≤2 neuropathy and/or hearing loss, alopecia of any grade, or autoimmune endocrinopathies on stable replacement therapy are permitted.\* 10. Female patients must agree to refrain from breastfeeding for 5 months after last study dose and satisfy one of: 1. Postmenopausal for ≥1 year prior to screening, or 2. Surgically sterile, or 3. Agreement to use one highly effective contraceptive method plus one additional barrier method from signing informed consent form (ICF) until 5 months after last study dose, or 4. Practice true abstinence\* when consistent with preferred lifestyle Periodic abstinence, withdrawal, spermicide-only, or lactational amenorrhea are unacceptable. Female/male condoms must not be used concomitantly. 11. Male patients, even surgically sterilized (i.e., post-vasectomy), must agree to either: 1. Use effective barrier contraception from ICF signing until 2 months after last DCSZ11 dose, or 2. Practice true abstinence\* when consistent with preferred lifestyle Exclusions as per Criterion 10. 12. Willingness and ability to comply with scheduled visits and procedures per protocol.
Exclusion criteria
1. Systemic anticancer therapy or investigational products within 6 months prior to first study dose. \*Note: Low-dose corticosteroids (oral prednisolone ≤10 mg daily or equivalent) and therapy with bisphosphonates or RANK ligand (RANKL) inhibitors are permitted.\* 2. Extensive radiotherapy (RT) ≤6 months prior to treatment initiation (\*≤7 days for palliative local RT outside chest/brain\*) OR unresolved RT-related toxicity requiring corticosteroids. 3. Second primary malignancy within 3 years, except: Adequately treated basal cell/locally confined squamous skin cancer Localized prostate cancer Carcinoma in situ of cervix/breast Resected colorectal adenomatous polyps Other malignancies not requiring active anticancer therapy. 4. Known active CNS metastases and/or carcinomatous meningitis. 5. Major surgery within 4 weeks or minor surgery within 2 weeks prior to first dose. All wounds must be fully healed without infection/dehiscence, with full recovery and no ongoing surgical complications. 6. Known hypersensitivity to any component of the study drug(s). 7. Prior immunotherapy discontinued due to: Grade ≥3 immune-related adverse events (irAEs) (except endocrinopathies controlled with replacement) Grade 2 myocarditis OR recurrent Grade 2 pneumonitis. 8. Active autoimmune disease requiring systemic immunosuppression within 2 years. Exempt: Physiologic hormone replacement (thyroxine, insulin, corticosteroids for adrenal/pituitary insufficiency). 9. Immunodeficiency diagnosis OR chronic systemic steroids (\>10 mg prednisolone-equivalent/day) or other immunosuppressants within 7 days prior to first dose. 10. History of lung RT \>30 Gy within 6 months prior to treatment. 11. History of (non-infectious) pneumonitis/interstitial lung disease (ILD) requiring steroids OR current pneumonitis/ILD. 12. History of allogeneic tissue/solid organ transplantation. 13. Live/live-attenuated vaccines within 4 weeks prior to treatment initiation. Inactivated vaccines permitted. 14. Active infection requiring systemic therapy. 15. Hepatitis B surface antigen (HBsAg)-positive with detectable HBV DNA. 16. Hepatitis C virus (HCV) infection with detectable HCV RNA at screening. 17. History within ≤6 months prior to first dose of: NYHA Class III/IV congestive heart failure Unstable angina Myocardial infarction Symptomatic ischemic heart disease Uncontrolled hypertension despite optimal therapy Persistent symptomatic arrhythmia \>Grade 2 Pericardial effusion/restrictive cardiomyopathy. Permitted: Chronic atrial fibrillation on stable anticoagulation. 18. Any condition compromising informed consent, confounding results, or limiting protocol compliance-including medical/psychiatric/social factors-that, per investigator judgment, contraindicates participation. 19. Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 2 years | The ratio of participants assessed with complete response (CR) or partial response(PR) as a best overall response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | 2 years | The ratio of subjects assessed with CR or PR or stable disease (SD) as a best overalresponse. |
| DRR (Durable Response Rate) | 2 years | DRR is defined as the proportion of objective response (CR and PR as determined by the investigator) lasting at least 6 months at any time within 12 months of initiation of treatment. |
| DOR (Duration of Response) | 2 years | DOR is defined as the time from the date when the PR is first recorded or better to the date when the disease progression is first recorded (for the responder, i.e., PR or better). Responders who did not record disease progress will be censored on the date that the last assessment was SD or better. |
| TTR (Response Time） | 2 years | TTR is defined as the time from the date of the first administration to the date of the first record of the objective tumor response (CR and PR determined by the investigator). |
| PFS (progression-free survival) | 2 years | PFS is defined as the duration until disease progression or death in participants fromthe first dose of immunization. |
| OS (Overall Survival) | 2 years | 0S is defined as the duration until death in participants from the first dose ofimmunization. |
| TTP (Time to Progression) | 2 years | TTP is defined as the time from the date of first dose to the date of first documented disease progression, as defined by standard disease criteria. |
Countries
China
Contacts
CONTACTXingchen Peng, Professor
CONTACTZiyu Xu
PRINCIPAL_INVESTIGATORXingchen Peng, Professor
West China Hospital
Outcome results
None listed