NSCLC avancé ou métastatique

CHUV

I

Any number of prior treatments

Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC) + cyclophosphamide + SOC treatment

Only patients receiving the maintenance/continuation of SOC treatment options mentioned below are permitted to enter the study.

CHUV

To determine the feasibility and safety of DC vaccine (autologous moDCs pulsed with NeoAg peptides [PEP-DC]) given in combination with low dose cyclophosphamide in patients with advanced or metastatic NSCLC who do not show progression after SOC therapy.

Inclusion criteria at screening

1. Histologically confirmed diagnosis of the NSCLC
2. Patients with metastatic, recurrent and/or unresectable NSCLC from stage IIIA (not amenable to radical treatment) to stage IVB provided they have not experienced disease progression on their current standard-of-care therapy at screening, as compared to the tumor assessment at the initiation of standard-of-care therapy as confirmed by CT/MRI.
3. Patients may have received any number of prior treatments without restriction and any prior immunotherapy before enrollment to the study. However, only patients receiving the maintenance/continuation of SOC treatment options mentioned below are permitted to enter the study.
4. Patient may receive only the following maintenance/continuation of SOC therapy during study treatment, as indicated in each case .
   a. Cohort 1: advanced or metastatic NSCLC of any histology without any actionable oncogenic driver treated by SOC. Maintenance pemetrexed and/or maintenance pemetrexed + pembrolizumab, pembrolizumab alone, nivolumab, or atezolizumab is allowed.
   b. Cohort 2: advanced or metastatic NSCLC with actionable oncogenic driver such as EGFR or ALK or ROS-1 -rearrangement, currently receiving osimertinib, alectinib, lorlatinib or crizotinib as per SOC in each disease entity
5. Top 10 personalized peptides (PEP) for the preparation of PEP-DC vaccine has been determined before screening.
6. Patients >18 years of age
7. ECOG performance status 0 or 1
8. Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 21 days prior registration.
9. Willing and able to comply with study procedures
   10.For women of childbearing potential (WOCBP: sexually mature women who have not undergone a hysterectomy, have not been naturally post-menopausal for at least 12 consecutive months or have a serum follicle-stimulating hormone (FSH) < 40 mIU/ml):
   a. Agreement to follow instructions for method(s) of contraception for the couple
   b. WOCBP must have a negative urine pregnancy test within 7 days, before registration.
   11.For men and their female partners: agreement to follow instructions for method(s) of contraception for the couple.
10. Patient is able to undergo leukapheresis

Exclusion criteria at screening

1. Pregnant or breast-feeding women
2. Other malignancy within 2 years prior study enrollment, except for those treated with surgical intervention as curative intent in remission.
3. Current, recent (within 4 weeks prior registration), or planned participation in an experimental drug study
4. Patients who show signs of progression according to RECIST 1.1 at screening
5. Planned SOC therapy other than the following:
   • Cohort 1: Maintenance pemetrexed and/or maintenance pemetrexed + pembrolizumab, pembrolizumab alone, nivolumab or atezolizumab
   • Cohort 2: osimertinib, alectinib, lorlatinib or crizotinib
6. Known hypersensitivity to any component of the study treatment
7. Any contraindication for using cyclophosphamide
8. Treatment with systemic immunosuppressive medications within 4 weeks prior vaccination. Patients who has to receive steroid treatment as premedication before premetrexed are eligible.
9. Administration of a live, attenuated vaccine within 8 weeks before registration.
   Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior registration or at any time during the study.
10. Positive serology defined by the following laboratory results:
    • Positive test for HIV
    • Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening).
     Patients with past/resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible, if HBV DNA test is negative.
     HBV DNA must be obtained in patients with positive hepatitis B core antibody prior start of study treatment.
    • Patients with active hepatitis C. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
11. Severe infections within 8 weeks prior registration including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or signs or symptoms of infection requiring oral or IV antibiotics within 8 weeks prior registration.
    • Patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic obstructive pulmonary disease exacerbation or for dental extraction) are eligible.
12. 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
13. Treatment with systemic immunostimulatory agents (including but not limited to IFN-α, IL-2) for any reason within 4 weeks or five half-lives of the drug, whichever is shorter, prior to registration.
14. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior registration.
    • Patients who are receiving acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) or physiologic replacement doses (i.e., prednisone 5−7.5 mg/day, or other) for adrenal insufficiency may be enrolled in the study.
    • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.