Atezolizumab as Induction Therapy in Non-small Cell Lung Cancer (PRINCEPS)

  • STATUS
    Recruiting
  • days left to enroll
    86
  • participants needed
    60
  • sponsor
    Gustave Roussy, Cancer Campus, Grand Paris
Updated on 25 February 2022
ct scan
platelet count
measurable disease
serum bilirubin level
metastasis
neutrophil count
pembrolizumab
cancer chemotherapy
mk-3475
adjuvant chemotherapy
atezolizumab
lung carcinoma

Summary

Based on the efficacy of immunotherapies in advanced disease with a reasonable safety profile/tolerability we could hypothetisize that, immunotherapy should work best in the situation of minimal residual disease, Two clinical trials are ongoing to test the role of immunotherapeutic agents in the adjuvant setting: PEARLS trial, a randomized phase III trial with anti-PD1 monoclonal antibody pembrolizumab (MK-3475 or pembrolizumab) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy, and the second randomized phase III trial (NCT02273375) will evaluate the efficacy of an anti-PD-L1 (MEDI 4736) for a maximum of 12 months versus placebo as adjuvant therapy in completed resected stage IB-IIIA NSCLC and completed standard ACT.

The role of immunotherapeutic approaches for NSCLC in the neoadjuvant setting is currently unknown. However, based on the survival efficacy of immunotherapeutic strategies in advanced NSCLC where the tumor has not been removed which could produce higher immunogenicity and based on the efficacy of neoadjuvant treatments in NSCLC, we propose to test the safety and efficacy of atezolizumab as neoadjuvant therapy in subjects diagnosed with stage I, II, or IIIA (non N2) NSCLC and who are deemed suitable for surgical resection.

Clinical staging of NSCLC is based on computed tomography (CT) of the chest and upper abdomen, brain CT or magnetic resonance imaging and 18F-FDG PETscan to rule out metastatic disease and assess the potential for curative-intent resection. Adjuvant chemotherapy will be performed according the standard clinical guidelines.

Details
Condition Nonsmall Cell Lung Cancer
Treatment Atezolizumab
Clinical Study IdentifierNCT02994576
SponsorGustave Roussy, Cancer Campus, Grand Paris
Last Modified on25 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 18 years
Histologically documented NSCLC
Clinical Stage IA ( 2 cm)-IIIA non N2 NSCLC eligible for surgical resection
Initial work-up including petscan and MRI for staging
Measurable disease, as defined by RECIST v1.1
Apt to surgical resection by a lobectomy or bilobectomy procedure
ECOG performance status of 0 or 1 (appendix 3)
Adequate hematologic and organ function, defined by the following laboratory results obtained within 14 days prior to registration
White blood cell (WBC) counts > 2.5 x 109/L
Absolut neutrophil count (ANC) 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to Day 1)
Platelet count 100 x 109/L
Hemoglobin 9.0 g/dL. Patients may be transfused to meet this criterion
AST, ALT, and alkaline phosphatase 2.5 X the upper limit of normal (ULN)
Serum bilirubin 1.5 X ULN. Patients with known Gilbert disease who have serum bilirubin level 3 X ULN may be enrolled
International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT) 1.5 X ULN -This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose
Creatinine clearance 60 mL/min on the basis of the Modification of Diet in Renal Disease (MDRD)
Serum albumin 2.5 g/dL
Calcemia 2.65 mmol/L or Ca 10 mg/dL
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days before the registration and must be willing to use two methods of contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for 5 months after last study drug administration. Sexually active males and their female partners must agree to use two methods of accepted and effective contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study
Information delivered to the patient and informed consent form signed by the patient
Ability to comply with the protocol procedures
Patient affiliated to a social security system or beneficiary of the same

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from study
entry
History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma for at least five years before registration
Prior therapy for lung cancer
Pregnant and breast feeding women
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab product
History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjgren's syndrome, Guillain-Barr syndrome, multiple sclerosis, Type I diabetes mellitus, vasculitis, or glomerulonephritis (see Appendix 5 for a more comprehensive list of autoimmune diseases). Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
History of HIV infection
Patients with active hepatitis B (chronic or acute) or hepatitis C Patients with past/resolved HBV infection (defined as the presence of anti-hepatitis B core antibody, IgG anti-HBs + and absence of HbsAg) are eligible. HBV DNA should be obtainedin these patients prior to Day 1
Patients positive for HCV antibody are eligible only if PCR is negative for
HCV RNA
Active tuberculosis
Severe infections within 4 weeks prior to registration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
Signs or symptoms of infection within 2 weeks prior to registration
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
Major surgical procedure other than for diagnosis within 28 days prior to registration or anticipation of need for a major surgical procedure during the course of the study
Prior allogeneic stem cell or solid organ transplant
History of any hematological disease not considered in complete remission for at least five years before registration
Administration of a live, attenuated vaccine within 4 weeks before registration or anticipation that such a live attenuated vaccine will be required during the study or for 5 months after study drug administration. Influenza vaccination should be given during influenza season only (approximately October to March)
Patients must not receive live, attenuated influenza vaccine (e.g., FluMist)
within 4 weeks prior to registration or at any time during the study
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior registration
Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to registration
Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the coordinating investigator. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed
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