Overview

Neoadjuvant Nivolumab in Resectable Non-Small-Cell Lung Cancer

Status:
Recruiting
Trial end date:
2027-10-31
Target enrollment:
0
Participant gender:
All
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 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Treatments:
Antibodies, Monoclonal
Nivolumab
Pembrolizumab
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 0-1.

- Adequate organ function as follows:

- Leukocytes ≥ 2,000/mm3.

- Absolute neutrophil count (ANC) ≥ 1000/mm3.

- Platelet count ≥ 100,000/mm3.

- Hemoglobin ≥ 9 g/dL.

- Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥40 mL/min (if using the
Cockcroft-Gault formula below):

Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL.

Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL.

- Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total
bilirubin < 3.0 mg/dL).

- AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 3 times the upper limit of normal.

- Subjects must have adequate lung function to permit surgical resection determined
by pre-enrollment pulmonary function tests to include DLCO.

- The effects of nivolumab on the developing human fetus are unknown. For this reason,
women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation and for up to 23 weeks after the
last dose of nivolumab. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately. Sexually active fertile men must use effective barrier
birth control if their partners are WOCBP for up to 31 weeks after the last dose of
nivolumab. WOCBP must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within two weeks of registration.
Women must not be breastfeeding.

- Patient understands the study regimen, its requirements, risks and discomforts and is
able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC
approved written informed consent form in accordance with regulatory and institutional
guidelines must be obtained before the performance of any protocol related procedures
that are not part of normal patient care. Subjects must be competent to report AEs,
understand the drug dosing schedule and use of medications to control AEs.

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.

- Women who are pregnant or nursing.

- Men with female partners (WOCBP) that are not willing to use contraception.

- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or
any other antibody targeting T cell co-regulatory pathways).

- Underlying medical conditions that, in the Investigator's opinion, will make the
administration of study drug hazardous or obscure the interpretation of toxicity or
adverse events.

- Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for
treatment of either a psychiatric or physical (e.g. infectious disease) illness.