A Phase II, Prospective, Randomized, Open Label, Multi-center Study of Tislelizumab Combined With Anlotinib and Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant With Resectable Stage II-IIIB Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Immunochemotherapy combined with antiangiogenic
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Tang-Du Hospital
- Enrollment
- 178
- Locations
- 1
- Primary Endpoint
- pathological complete response (pCR) in Intent-to-Treat (ITT) analysis set
- Status
- Not Yet Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a Phase II, prospective, randomized, open label, controlled, multi-center study, aim to evaluate the activity of Tislelizumab and Anlotinib and chemotherapy compared with Tislelizumab and chemotherapy before surgery, followed by Tislelizumab alone as adjuvant therapy. The primary objective of this study is to evaluate and compare pathological complete response rate(pCR).
Investigators
Eligibility Criteria
Inclusion Criteria
- •aged 18\~75 years old
- •histologically confirmed stage IIA to stage IIIB (IIIB term T2/3/4N2) non-small cell lung cancer (staging based on AJCC 9th edition)
- •ECOG PS score of 0-1;
- •patients are asked to provide an archived tumor tissue sample (FFPE tissue block or approximately ≥ 6 freshly cut unstained FFPE sections) and a pathology report of this baseline sample for PD-L1 and other biomarker analysis). Biopsy samples are requested at baseline if there are no available archival samples or samples are unavailable.
- •Adequate organ and marrow function
- •expected survival ≥ 3 months;
- •be evaluated by a thoracic surgeon and confirmed to be eligible for R0 resection for the purpose of radical treatment
- •At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline
Exclusion Criteria
- •those with a known history of CNS metastases;
- •patients with EGFR mutations or ALK translocations;
- •those with imaging (CT or MRI) showing tumor invasion of a major blood vessel (e.g., pulmonary artery or superior vena cava) or those with a high likelihood of fatal hemorrhage due to tumor invasion of a major blood vessel during the follow-up study;
- •prior treatment with immune checkpoint inhibitors, including but not limited to anti-CTLA-4, anti-PD-1 and anti-PD-L1 therapeutic antibodies, and OX-40;
- •previous systemic antivascular therapy;
- •current participation in an interventional clinical trial or receipt of another investigational drug or medical intervention within 4 weeks;
- •presence of active hemoptysis, active diverticulitis, abdominal abscess, gastrointestinal obstruction (or other factors affecting the absorption of oral medications such as inability to swallow, nausea and vomiting, abnormal physiologic function, malabsorption syndrome, etc.) that require clinical intervention
- •the presence of any signs or history of bleeding constitution; the presence of unhealed wounds, ulcers, or fractures in patients who have experienced any bleeding or hemorrhagic event ≥ CTCAE Grade 3 within 4 weeks prior to enrollment;
- •class III-IV congestive heart failure with poorly controlled and clinically significant arrhythmias (including QTcF ≥450ms in men and ≥470ms in women);
- •difficult-to-control hypertension;
Arms & Interventions
Tislelizumab with anlotinib and platinum-based chemotherapy + Adjuvant Tislelizumab
Intervention/treatment: Tislelizumab 200mg iv，d1，q3w， Anlotinib 10mg，po，qd1-14，q3w， Cisplatin 75 mg/m\^2 by IV infusion Q3W, given on cycle day 1 Carboplatin AUC of 5 on Day 1 of each 3-week cycle Paclitaxel 175mg/m2 on Day 1 of each 3-week cycle(SQ only) Albumin-bound paclitaxel 260mg/m2，on D1 IV infusion Q3W or 130mg/m2 on D1D8 IV infusion Q3W for each cycle(SQ only) Pemetrexed 500 mg/m2 on Day 1 of each 3-week cycle(NSQ only) Adjuvant: 4 weeks(±7 Days) following surgery, participants receive no more than 16 cycles (cycle length: 3 weeks) of Tislelizumab \[200 mg, IV; given on cycle day 1\].
Intervention: Immunochemotherapy combined with antiangiogenic
Tislelizumab with platinum-based chemotherapy + Adjuvant Tislelizumab
Tislelizumab 200mg iv，d1，q3w， Cisplatin 75 mg/m\^2 by IV infusion Q3W, given on cycle day 1 Carboplatin AUC of 5 on Day 1 of each 3-week cycle Paclitaxel 175mg/m2 on Day 1 of each 3-week cycle(SQ only) Albumin-bound paclitaxel 260mg/m2，on D1 IV infusion Q3W or 130mg/m2 on D1D8 IV infusion Q3W for each cycle(SQ only) Pemetrexed 500 mg/m2 on Day 1 of each 3-week cycle(NSQ only) Adjuvant: 4 weeks(±7 Days) following surgery, participants receive no more than 16 cycles (cycle length: 3 weeks) of Tislelizumab \[200 mg, IV; given on cycle day 1\].
Intervention: Immunochemotherapy
Outcomes
Primary Outcomes
pathological complete response (pCR) in Intent-to-Treat (ITT) analysis set
Time Frame: through study completion, an average of 1 year
pathological complete response (pCR): defined as no residual tumor cells in the surgically resected tumor specimen and all sampled regional lymph nodes after neoadjuvant treatment.