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

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.

Interventions

• Drug [225Ac]Ac-DOTATATE
  During the dose escalation phase, the "3+3" dose escalation method was adopted. There were two dose groups: the single-dose administration dose of the first dose group was 90 kBq/kg, and that of the second dose group was 120 kBq/kg.During the dose expansion phase, the subjects received the RP2D dose of the \[225Ac\]Ac-DOTATATE injection. The administration method, combination therapy, etc. were all the same as those in the dose escalation phase.

Primary outcome measures

• 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]
• 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]

Secondary outcome measures (9)

• 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. [Time frame: 12 months after last dose administration]
• 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. [Time frame: 12 months after last dose administration]
• 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. [Time frame: 12 months after last dose administration]
• 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. [Time frame: 12 months after last dose administration]
• During the dose expansion phase, other efficacy endpoint indicators will be evaluated. [Time frame: 12 months after last dose administration]
• During the dose expansion phase, other efficacy endpoint indicators will be evaluated. [Time frame: 12 months after last dose administration]
• During the dose expansion phase, other efficacy endpoint indicators will be evaluated. [Time frame: 12 months after last dose administration]
• During the dose expansion phase, other efficacy endpoint indicators will be evaluated. [Time frame: 12 months after last dose administration]
• During the dose expansion phase, the safety is evaluated. [Time frame: 6 months after last dose administration]

Eligibility criteria

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 1.
• 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.

• Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, IUDs, etc., during treatment and within 6 months of the last use of the trial drug.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Cancer Hospital & Institute — Beijing

Identifiers

NCT: NCT07413042 · IIT-XT024-1-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗