Non-small cell lung cancer (NSCLC) with PDL1 expression =50% which does not achieve tumour clearance with anti-PD1 treatment Cancer
Conditions
Interventions
The NEOVACC doggybone personalised cancer vaccines (dbPCV) will be administered by PharmaJet Stratis Needle-free injection system. Participants will receive a 2mg/ml dose of dbPCV in 2 divided doses
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Written and informed consent obtained from the participant and agreement from the participant to comply with the requirements of the trial. 2. Aged = 18 years old. 3. Histologically proven advanced or recurrent NSCLC with PDL1 expression =50% and where anti-PD1 immunotherapy is licensed as standard of care treatment. 4. Has completed at least 3 cycles of SOC IO and demonstrates partial response, stable disease or progression deemed to be such that can wait for production of PCV. 5. Tumour accessible for sufficient sample to be taken for research e.g. surgical biopsy or repeat core biopsies (6 passes) in the opinion of the treating oncologist and physician performing the biopsy. 6. Considered fit enough to undergo trial specific procedures. 7. ECOG performance status of 0-1. 8. Venous access sufficient for collection of the blood/apheresis samples.
Exclusion criteria
Exclusion criteria: 1. Demonstrated a complete response from previous treatments according to RECIST criteria. 2. In the physician’s view are likely to have sufficient benefit from anti-PD1 treatment alone. 3. Evidence of rapid disease progression, who cannot wait for vaccine production and must seek alternative treatment options. 4. Active autoimmune disease likely to pose a risk for the safe administration of anti-PD1 or other immune activating agents; exceptions to this are atopic dermatitis and psoriasis not requiring systemic treatment. Topical and inhaled steroids are allowed. 5. Significant immune related adverse event requiring anti-PD1 to be stopped or necessitating ongoing systemic immunosuppressive treatment. Patients who have required mycophenolate or infliximab for management of IO related toxicities are not eligible. 6. Currently receiving any form of chemotherapy and have received chemotherapy in the previous 9 weeks prior to screening. 7. Any other experimental medications during trial participation and within 30 days of consent. 8. History of confirmed inflammatory bowel disease. 9. Previous organ transplantation. 10. Known brain metastases. 11. Greater than 10mg Prednisolone equivalent per day unless for replacement purposes (e.g. adrenal insufficiency). 12. Active or previous malignancies of other types, which in the Investigator’s opinion would mean they are not a good candidate for the clinical trial; specifically excluded are patients with malignancies that even in the early stages carry a high immunosuppressive burden (for example CLL, Multiple myeloma). 13. Received anti-PD1 or anti-PD-L1 in prior line of treatment. 14. Other vaccination within a week of trial vaccination. 15. Known diagnosis of HIV or active hepatitis B or C. Participants who are HBV carriers and receiving anti-viral prophylaxis are excluded. 16. Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the Investigator, may affect the participant’s ability to provide informed consent and undergo trial procedures. 17. Women of child bearing potential (WOCBP) who are currently pregnant, lactating or breastfeeding. 18. WOCBP or participants with partners of child bearing potential who are unable or unwilling to use contraception during the trial. 19. Known allergy to any component of the IMP.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility of making and delivering the dbDNA vaccines is measured by confirming whether the NEOVACC personalised vaccines (dbPCV) were delivered in a timely manner at the time of first vaccination. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measures: 1. Safety and tolerability of vaccination in combination with anti-PD1 is measured using adverse event reporting and clinical, biochemical and radiological assessments from first vaccination to end of treatment (up to 2 years as standard of care anti-PD1 treatment). 2. Overall Response Rate is measured using CT scan chest/abdomen/pelvis at screening, baseline, week 12, week 24 and then every 12 weeks during treatment and at the end of trial, as per standard of care imaging. 3. Time to disease progression is measured using CT scan chest/abdomen/pelvis at screening, baseline, week 12, week 24 and then every 12 weeks during treatment and at the end of trial, as per standard of care imaging. 4. Overall survival is measured at the end of trial. Exploratory Outcome Measure: Vaccine induced T cell response is measured using ELISPOT on blood samples, ELISA on plasma samples, single cell RNA and TCR sequencing in blood and tissue samples; and immunofluorescence of protein expression in tissue. This will be measured throughout the trial using blood samples, tissue sampling after 6 doses of the dbDNA vaccine, and FPE tissue related to skin or bowel toxicities collected as part of standard of care and surplus to diagnostic requirement. | — |
Countries
England, United Kingdom
Contacts
Public ContactHelen Eccleson
Outcome results
None listed