Neoadjuvant Camrelizumab Plus Apatinib or Platinum-based Chemotherapy for Potentially Resectable (Resectable and Initially Unresectable) II-III Non-small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Camrelizumab
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Enrollment
- 89
- Locations
- 1
- Primary Endpoint
- Major pathologic response (MPR)
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
Immunotherapy with anti-programmed death 1 (PD-1) antibodies has revolutionized the treatment of metastatic and advanced NSCLC, but its application in neoadjuvant setting has not been well established. Results from a pilot clinical study reported the safety and feasibility of neoadjuvant PD-1 blockade. There are several neoadjuvant immunotherapy (NEOSTAR, LCMC3, NADIM, IMpower131) ongoing, and the preliminary results are reported in 2019 American Society of Clinical Oncology, which show promising therapeutic prospect. However, the therapeutic response rate (major pathologic response [MPR]) are not so good (20% - 45%) for PD-1 inhibitor monotherapy. To improve the therapeutic response, the investigators design a multiple-canter, open-label, phase II trial for stage II-III potentially resectable (resectable and initially unresectale) NSCLC. The participants will receive neoadjuvant PD-1 inhibitor (camrelizumab) combined with antiangiogenic drug (apatinib) or platinum-based chemotherapy.
Detailed Description
Detailed Description: This is a multiple-canter, open-label, phase II trial, 2-4 cycles treatment will be planned as neo-adjuvant therapy for NSCLC participants in stage II-III. Study design: Participants: Newly diagnosed Resectable and Initially Unresectale II-III NSCLC without EGFR/ALK mutation. Treatment: Group A：camrelizumab 200 mg q3w i.v. for 2-4 cycles, platinum-based chemotherapy q3w i.v for 2-4 cycles before surgery. Group B：camrelizumab 200 mg q3w i.v. for 2-4 cycles, apatinib 250mg qd po 3w/cycle for 2-4 cycles before surgery; Endpoints: Primary objectives are to assess MPR and safety. Secondary objective is to assess 2-year overall survival (OS), disease-free survival (DFS), OS etc. Exploratory end point is to explore biomarkers.
Investigators
Peng Zhang
Director of thoracic department
Shanghai Pulmonary Hospital, Shanghai, China
Eligibility Criteria
Inclusion Criteria
- •Aged 18-75 years;
- •Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1;
- •Histological or cytological diagnosis of NSCLC by needle biopsy, and clinical stage II-III according to the TNM classification (8th edition) validated by radiological examination or EBUS;
- •At least 1 measurable lesion according to RECIST 1.1;
- •Life expectancy is at least 12 weeks;
- •Adequate hematological function, liver function and renal function:
- •Hemoglobin ≤ 90 g/L (which can be maintained or exceeded by blood transfusion);
- •Absolute neutrophil count (ANC) ≤ 1.5 \*10\^9/L;
- •Platelet count ≤ 100 \* 10\^9/L;
- •Total bilirubin ≤ 1.5 times of upper limit of normal (ULN);
Exclusion Criteria
- •The patient has undergone any systemic anti-cancer treatment for NSCLC, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment, immunotherapy or Chinese medicine treatment, etc. (excluding the malignant tumors that were resected radically and did not recurrent more than 5 years);
- •Non-squamous cell carcinoma with EGFR active mutation positive or ALK rearrangement;
- •The patient suffered from other cancers (except cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor \[including Ta and Tis\]) within 5 years before the enrollment;
- •The patient suffers from any active autoimmune disease or have the history of autoimmune disease, such as uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy), tuberculosis; Note: The patients with complete remission of childhood asthma and without any interventions in adult life could be included. The patients with skin diseases (like vitiligo, psoriasis or alopecia) who do not need systematic therapy could be included.
- •Suffering or having the history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiological pneumonia, drug-induced pneumonia, radiologically confirmed active pneumonia, or severe impairment of lung function;
- •Participants who were systemically treated with corticosteroids (prednisone or other corticosteroids \>10 mg/ day) or other immunosuppressive agents within 2 weeks prior to first administration. In the absence of active autoimmune disease, inhaled or topical corticosteroids and adrenal hormone replacement therapy with a dose of less than 10 mg/ day of prednisone are permitted;
- •Allergy to the test drug;
- •The patient is a carrier of active hepatitis B, hepatitis C or HIV;
- •Pregnancy or breast-feeding women; child-bearing participants who could not or are unwilling to take contraceptive measures.
- •Patients with eurological or psychiatric disorders history were lack of treatment compliance;
Arms & Interventions
camrelizumab + apatinib
Neoadjuvant treatment stage: camrelizumab 200mg, q3w, i.v., 2-4 cycles; apatinib 250 mg, qd, p.o. 3 weeks per cycle, 2-4 cycles, then receive chest CT evaluation. Surgery stage: the patients will receive radical surgery 3-4 weeks after the neoadjuvant treatment. Adjuvant treatment stage: according to the NCCN guidelines.
Intervention: Camrelizumab
camrelizumab + platinum-based chemotherapy
Neoadjuvant treatment stage: camrelizumab 200mg, q3w, i.v., 2-4 cycles; platinum-based chemotherapy (squamous: carboplatin AUC5, gemcitabine 1000mg/m2; non-squamous: carboplatin AUC5, pemetrexed 500mg/m2) q3w, i.v., 2-4 cycles, then receive chest CT evaluation. Surgery stage: the patients will receive radical surgery 3-4 weeks after the neoadjuvant treatment. Adjuvant treatment stage: according to the NCCN guidelines.
Intervention: Camrelizumab
Outcomes
Primary Outcomes
Major pathologic response (MPR)
Time Frame: up to 5 months
MPR is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery.
Secondary Outcomes
- 2-year OS(up to 27 months)
- Objective response rate (ORR)(up to 4 months)
- Disease-free survival (DFS)(up to 60 months)
- Overall survival (OS)(up to 63 months)
- Safety: frequency of severe adverse events(up to 6 months)