Clinical trial NCT05900921: Trilaciclib Prior to Chemotherapy Plus Tislelizumab as 1L Treatment for Advanced Squamous Non-Small-Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Advanced Squamous Non-Small-Cell Lung Cancer
Lead sponsor: Sichuan University
Sponsor class: OTHER
Collaborators: name: Chengdu First People's Hospital
name: Chengdu Second people's hospital
name: Chengdu Seventh People's Hospital
name: Mianyang Central Hospital
name: Shanxi Provincial Cancer Hospital
name: Shandong Cancer Hospital and Institute
name: Heilongjiang Provincial Cancer Hospital
name: Enshi Central Hospital
name: Neijiang Hospital of Traditional Chinese Medicine
First posted: 2023-06-13
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: incidence of grade ≥3 Neutrophil count decreased
timeFrame: Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator
Secondary outcomes:
measure: 1. incidence of other indicators of Myelosuppression(Grade 4 Neutrophil count decreased, grade 3 or 4 thrombocytopenia, grade 3 or 4 anemia, febrile neutropenia)
timeFrame: Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator
measure: Usage rate of Supportive Intervention(Granulocyte colony-stimulating factor (G-CSF), platelet transfusion, red blood cell transfusion (week 5 and later), erythropoietin (ESA), iron, recombinant human interleukin-11, and/or thrombopoietin (TPO))
timeFrame: Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator
measure: Progress free survival (PFS)
timeFrame: untill Progressive Disease(PD) or death(up to 24 months)
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to 24 months)
measure: Objective Response Rate (ORR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
Study officials:
affiliation: West China Hospital
name: Yongsheng Wang
role: PRINCIPAL_INVESTIGATOR
References: