A Phase I Study to Evaluate the Safety and Preliminary Efficacy of [225Ac]Ac-DOTATATE Injection Combined With Tislelizumab in the Maintenance Treatment Period for Patients of Extensive-stage Small Cell Lung Cancer (ES-SCLC) With Somatostatin Receptors (SSTR)+ as First-line Treatment
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Peking University Cancer Hospital & Institute
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- During the dose expansion phase, the efficacy of [225Ac]Ac-DOTATATE injection at the RP2D dose for maintenance treatment in first-line therapy for SSTR-positive ES-SCLC patients when used in combination with tislelizumab was evaluated.
Overview
Brief Summary
This is a phase I study to evaluate the safety and preliminary efficacy of [225Ac]Ac-DOTATATE injection combined with tislelizumab in the maintenance treatment period for patients of extensive-stage small cell lung cancer (ES-SCLC) with somatostatin receptors (SSTR)+ as first-line treatment.Patients with ES-SCLC who have completed the induction therapy of first-line standard treatment and are yet to enter the maintenance treatment period are planned to be enrolled.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must have the ability to understand and sign an approved informed consent form (ICF).
- •Patients must be \>= 18 and \<＝80 years of age.
- •Extensive-stage small cell lung cancer that requires histopathological or cytological confirmation.
- •Presence of at least 1 measurable site of disease (based on RECIST 1.1).
- •ECOG score of 0 or
- •SSTR-PET positive.
- •Sufficient bone marrow capacity and organ function:
- •Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 ml/min (Cockcroft Gault formula).
- •Hemoglobin≥90g/L, neutrophil count ≥1.5×10\^9/L, platelets≥100×10\^9/L. Serum total bilirubin ≤1.5×ULN. Serum albumin ≥30g/L. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5×ULN，or ALT/AST≤5×ULN with liver metastases.
- •Partially activated prothrombin time (APTT) ≤1.5 x ULN.
Exclusion Criteria
- •Pregnant or lactating females.
- •Received systemic antitumor therapy such as targeted therapy, immunotherapy, antitumor herbal therapy, chemotherapy within 4 weeks prior to initiation of study treatment.
- •Uncontrolled congestive heart failure.
- •uncontrolled diabetes mellitus, including baseline fasting glucose \> 2 x ULN.
- •Known hypersensitivity to Lutetium\[177Lu\] Oxodotreotide Injection or \[225Ac\]Ac-DOTATATE Injection and their excipients.
- •Other treatment options (e.g., chemotherapy, targeted therapy) that, in the opinion of the investigator, are more appropriate for the patient than the treatment provided in the study based on the patient's disease characteristics.
- •Unsuitable for the study for any reason, in the opinion of the investigator.
Arms & Interventions
[225Ac]Ac-DOTATATE
The subjects received the [225Ac]Ac-DOTATATE injection combined with tislelizumab. The tislelizumab was administered at a fixed dose of 200mg on day 1, and was given every 3 weeks. The [225Ac]Ac-DOTATATE injection was administered once every 6 (±1) weeks, with a maximum of 4 administrations.
Intervention: [225Ac]Ac-DOTATATE (Drug)
Outcomes
Primary Outcomes
During the dose expansion phase, the efficacy of [225Ac]Ac-DOTATATE injection at the RP2D dose for maintenance treatment in first-line therapy for SSTR-positive ES-SCLC patients when used in combination with tislelizumab was evaluated.
Time Frame: 12 months after last dose administration
PFS
During the dose escalation phase, the efficacy of [225Ac]Ac-DOTATATE injection at the RP2D dose for maintenance treatment in first-line therapy for SSTR-positive ES-SCLC patients when used in combination with tislelizumab was evaluated.
Time Frame: 6 months after last dose administration
Incidence and severity of adverse events (AEs) DLT MTD RP2D
Secondary Outcomes
- During the dose escalation phase, the efficacy of [225Ac]Ac-DOTATATE injection for use as a maintenance treatment in the first-line therapy of SSTR-positive ES-SCLC patients when combined with tislelizumab was evaluated.(12 months after last dose administration)
- During the dose expansion phase, other efficacy endpoint indicators will be evaluated.(12 months after last dose administration)
- During the dose expansion phase, the safety is evaluated.(6 months after last dose administration)