Trilaciclib Prior to Chemotherapy Plus Tislelizumab as 1L Treatment for Advanced Squamous Non-Small-Cell Lung Cancer

A Phase II, Randomized, Open-label Trial of Trilaciclib Prior to Chemotherapy Plus Tislelizumab as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer

The purpose of this study is to explore the myeloprotective effects of trilaciclib in advanced squamous non-small cell lung cancer patients receiving a combination therapy of chemotherapy(carboplatin+paclitaxel) and immune checkpoint inhibitor (tislelizumab), as well as enhancing antitumor efficacy and possible immunological synergies.

This is a phase 2 clinical trial that is randomized, controlled, multicenter, and prospective in design. A total of 132 patients with advanced, untreated squamous non-small cell lung cancer will be randomly assigned 1:1 to receive or not receive Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction). Following induction, patients will receive or not receive trilaciclib with tislelizumab for every 3 weeks until PD, intolerable toxicity, withdrawal, or death. If subsequent chemotherapy is indicated for patients after first-line progression, trilaciclib will be provided to observe the myeloprotective effect in second-line treatment. The study is expected to commence recruitment in mainland China in about May 2023. It is expected that the trial will end in December 2025.

Inclusion Criteria:

• 1. Age ≥ 18 years old and ≤ 75 years old, male or female;
• 2. Unresectable stage ⅢB and Ⅳ squamous non-small cell lung cancer confirmed by histology or cytology;
• 3. Have not received systemic anti-tumor therapy for advanced tumors in the past;
• 4. There is at least one measurable lesion that meets the RECIST1.1 criteria;
• 5. Patients with asymptomatic brain metastases or stable symptoms after treatment of brain metastases;
• 6. Laboratory tests meet the following criteria: Hemoglobin ≥ 100 G/L (female), 110 G/L (male) Neutrophil count ≥ 2 × 10^9/L Platelet count ≥ 100 × 10^9/L; Creatinine ≤ 15 mg/L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula); Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 3 × ULN or ≤ 5 × ULN (for patients with liver metastases); Albumin ≥ 30g/L;
• 7.ECOG PS score 0-1;
• 8. Expected survival time ≥ 3 months;
• 9. Women: All women with potential fertility must have negative serum pregnancy test results during the screening period, and must take reliable contraceptive measures from the signing of informed consent to 3 months after the last administration;
• 10. Understand and sign the informed consent form.

Exclusion Criteria:

• 1. Patients with the following diseases: Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive); Interstitial lung disease/lung inflammation; Active, suspected autoimmune disease requiring systemic treatment in the past 2 years;
• 2. Vaccination of live attenuated vaccine within 4 weeks before enrollment, or expected to require vaccination of live attenuated vaccine during the study period;
• 3. Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA class III or IV);
• 4. Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment 5. QTcF > 480 msec at screening and > 500 msec for patients with ventricular pacemakers
• 6. Previous hematopoietic stem cell or bone marrow transplantation
• 7.Hypersensitivity to the study drug or its components;
• 8. Those who are not considered suitable to participate in the study by the investigator.