ICIs Neoadjuvant Therapy in Resectable Non-Small-Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab
- Conditions
- High-Risk Resectable NSCLC
- Sponsor
- Second Affiliated Hospital, School of Medicine, Zhejiang University
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Safety and Adverse effects
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting.
Detailed Description
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 or anti-PD-L1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically proven non-small-cell lung cancer (core biopsy required).
- •Squamous or non-squamous histology.
- •Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at The Second Affiliated Hospital Zhejiang University School of Medicine.
- •Either a formalin fixed paraffin block or a minimum of fifteen 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling). This can be obtained from archived tissues, or from a new biopsy if needed.
- •Stage - High risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at The Second Affiliated Hospital Zhejiang University School of Medicine. This may include clinical stage IA3 (≥2cm), II and IIIA(see Appendix A). Subjects with N3 nodal involvement are not included.
- •ECOG performance status 0-
- •Adequate organ function as follows:
- •Leukocytes ≥ 2,000/mm
- •Absolute neutrophil count (ANC) ≥ 1000/mm
- •Platelet count ≥ 100,000/mm
Exclusion Criteria
- •Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- •Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
- •Administration of chemotherapy or any other cancer therapy in the pre-operative period.
- •Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia).
- •Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
- •Subjects with a history of symptomatic interstitial lung disease.
- •Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
- •Known positive history or positive test for Human Immunodeficiency Virus or
- •Acquired ImmunoDeficiency Syndrome (AIDS).
- •History of allergy to study drug components.
Arms & Interventions
Single arm
Intervention: Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab
Outcomes
Primary Outcomes
Safety and Adverse effects
Time Frame: 8 weeks
Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites. Safety will also be measured by recording Grade 3 and 4 CTCAE 4.03 listed adverse events that occur while a subject is participating in the study.
Secondary Outcomes
- Radiographic Response(5 weeks)
- Pathologic Response(6 weeks)
- Rate of Enrollment(8 weeks)