A Phase II, Open-Label, Single-Arm, Prospective Clinical Study to Investigate the Efficacy and Safety of Tislelizumab Combined With Anlotinib as Maintenance Therapy Following Tislelizumab and Chemotherapy for Treatment Naïve Extensive Stage Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Anlotinib
- Conditions
- Extensive Stage Small Cell Lung Cancer
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- 1-year PFS rate assessed by investigator in maintenance phase-patient analysis set per RECIST v1.1.
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open-label, single-arm, prospective phase 2 study, evaluating the efficacy and safety of tislelizumab combined with Anlotinib as maintenance therapy following tislelizumab and chemotherapy for treatment naïve extensive stage small cell lung cancer.
Detailed Description
The study included screening period, treatment period (including induction and maintenance), safety follow-up and survival follow-up periods. Induction treatment will be administered on a Q3W cycle for 4 cycles. Following induction treatment, patients who have received 4 cycles of tislelizumab and platinum-based chemotherapy and meet the following criteria will enter a maintenance treatment phase with tislelizumab and Anlotinib. Patients have an ongoing response per RECIST v1.1 criteria of SD or better assessed by the investigator according to RECIST v1.1（Patients will be eligible to enter maintenance phase if chemotherapy interruption due to toxicity, but at least 3 cycles of tislelizumab combined with chemotherapy are completed and assessed as CR, PR or SD according to RECISTv1.1 criteria）. Excluded patients with central cavitary ES-SCLC, or tumor invading or adjacent to large vessels as shown by imaging, and likely to invade large vessels and cause fatal bleeding assessed by the investigator. During the maintenance treatment period prophylactic cranial irradiation (PCI) is permitted as per local standard of care. Treatment may continue until 1) disease progression as assessed by the investigator per RECIST v1.1, 2) loss of clinical benefit as assessed by the investigator, 3) unacceptable toxicity, or 4) withdrawal of informed consent, whichever occurs first, 5) study treatment duration reached 2 years (including induction and maintenance period). Per investigator's discretion, patients who may continue to benefit from study treatment after progressive disease must meet the following criteria in order to be treated and documented in the study records: Absence of symptoms and signs indicating clinically significant progression of disease and absence of worsening of laboratory values indicating disease progression. Stable ECOG performance status ≤ 1 Absence of rapid progression of disease or of progressive tumor at critical anatomical sites (eg,cord compression) that requires urgent alternative medical intervention Investigators must obtain written informed consent for treatment beyond radiologic disease. Study treatment will be administered for up to 2 years (including induction and mantenance period).
Investigators
Fan Yun, MD
Director of department
Zhejiang Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed ES-SCLC, defined by the American Joint Committee on Cancer (AJCC) 8th edition or the Veterans Administration Lung Study Group (VALG) staging system.
- •No prior treatment for ES-SCLC. (Patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of ≥ 6 months between the completion of chemotherapy, radiotherapy, or chemoradiotherapy and diagnosis of ES-SCLC).
- •ECOG performance status ≤
- •Life expectancy ≥ 3 months.
- •Adequate organ function as indicated by the following laboratory values (obtained ≤ 7 days before first dose):
- •Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L，hemoglobin ≥ 90 g/L.
- •International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x upper limit of normal (ULN).
- •Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
- •Serum total bilirubin ≤ 1.5 x ULN.
- •Aspartate and alanine aminotransferase (AST and ALT) ≤ 2.5 x ULN, or AST and ALT ≤ 5 x ULN for patients with liver metastases.
Exclusion Criteria
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis:
- •Patients with a history of treated and, at the time of screening, asymptomatic central nervous system (CNS) metastases are eligible if they meet all the following:
- •only supratentorial metastases allowed.
- •No radiotherapy for the central nervous system within 14 days prior to screening.
- •Untreated and Asymptomatic patients with brain metastasis brain metastases can be included in the study after judgment by the investigators, but regular brain imaging examinations of the disease site are required.
- •Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints.
- •Received prior anti-VEGF or VEGFR TKI agents including but not limited to Anlotinib.
- •Treatment with any approved systemic anti-cancer therapy or systemic immune-stimulatory agents (including but not limited to interferons, interleukin IL-2, and tumor necrosis factor) within 28 days prior to initiation of study treatment.
- •Clinically uncontrolled pleural effusion, ascites, pericardial effusion that requires treatment and may affect study treatment estimated by investigator.
- •History of allergic reactions to any study drugs or any component of the preparation or any component of the container.
Arms & Interventions
Tislelizumab combined with Anlotinib
Intervention: Anlotinib
Tislelizumab combined with Anlotinib
Intervention: Tislelizumab
Outcomes
Primary Outcomes
1-year PFS rate assessed by investigator in maintenance phase-patient analysis set per RECIST v1.1.
Time Frame: Start of maintenance therapy until 1-year follow-up
PFS is defined as the time from the first dose of study drug(s) in maintenance phase to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever occurs first.
Secondary Outcomes
- TEAE(up to 2 year)
- DCR(up to 2 year)
- PFS(up to 2 year)
- ORR(up to 2 year)
- OS(up to 2 year)
- DOR(up to 2 year)