Browsing Over 392 Presentations
Q&A (ID 1)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Q&A (ID 2)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Break (ID 3)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Q&A (ID 4)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Q&A (ID 5)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Break (ID 6)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Q&A (ID 7)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Q&A (ID 8)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Panel session (ID 9)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
Conclusions (ID 10)
- Tullia C. Bruno (Pittsburgh, PA, United States of America)
LBA6 - UCPVax therapeutic vaccination promotes cytotoxic and Th1 polarized antitumor CD4 T cells and epitope spreading in patients with advanced non-small cell lung cancer (ID 11)
- Olivier Adotevi (Besancon, France)
Abstract
Background
The stimulation of antitumor CD4 T helper response represents a critical requirement for therapeutic cancer vaccine effectiveness. In this context, we developed a Th1-inducer anticancer peptide vaccine derived from telomerase called UCPVax (Dosset et al. Clin Can Res 2012). The safety and efficacy of UCPVax therapeutic vaccination were recently reported in metastatic non-small cell lung cancer (NSCLC) phase I/II trial (Adotévi et al., J Clin Oncol 2022, NCT02818426). Here, we described the immunological responses promoted by UCPVax.
Methods
Immune monitoring was performed in 52 patients with refractory metastatic NSCLC previously vaccinated with three doses of UCPVax for six times (one per week) followed by boost every two months for one year. Blood samples were collected before and at different times after vaccination. Vaccine-specific CD4 T cell responses and epitope spreading were evaluated by IFN-γ ELISPOT assay. MHC class II pentamer staining and intracellular cytokine secretion assay were used for the assessment of phenotype function and polarization of antigen specific CD4 T cells. Vaccine induced antibody response was measured by ELISA.
Results
Seventy % of patients mounted strong UCP-specific CD4 T cells after vaccination regardless the dose level. UCPVax induced de novo and strong UCP-specific CD4 T-cell response and the intensity of the response increased according to the number of vaccinations. The UCP-specific CD4 T cells were effector memory phenotype, showed cytotoxic potential and (IFN-γ,TNF-a, IL-2)+ Th1 polarization which were maintained in long-term responders. Increased level of antibody response against UCP was found in 45% of patients which was correlated to the number of UCP-CD4 T cells. Furthermore, UCPVax induced epitope spread responses against various tumor antigens in most of patients analyzed. Finally, patients displayed polyfunctional anti-UCP CD4 response and epitope spreading had a better survival.
Conclusions
UCPVax vaccination promotes highly functional and long-lasting tumor specific CD4 T cell responses associated with the improvement of patients’ survival.
Clinical trial identification
NCT02818426.
Legal entity responsible for the study
O. Adotevi.
Funding
National Cancer Institute INCa France PHRC program.
Disclosure
O. Adotevi: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Non-Financial Interests, Personal, Principal Investigator: MSD. V. Westeel: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Amgen, Lilly, MSD, BMS. C. Borg: Financial Interests, Personal, Advisory Role: MSD Oncology, Roche; Financial Interests, Institutional, Sponsor/Funding: Bayer. All other authors have declared no conflicts of interest.
LBA2 - Phase II study of PD-L1 Expression Guidance on Neoadjuvant (NA) Nivolumab (Nivo) Monotherapy with or without platinum-doublet Chemotherapy in Resectable NSCLC (ID 13)
- Si-Yang Liu (Guangzhou, China)
Abstract
Background
We profiled clinical and biomarker data from this prospective, multicenter, phase II study evaluating the efficacy and safety of NA nivo with or without platinum-doublet chemotherapy based on PD-L1 status (NCT04015778).
Methods
Patients (pts) had resectable clinical stage IIA-IIIB (AJCC 8th) NSCLC and ECOG PS 0/1 with no EGFR/ALK variations. Pts received mono-nivo 360mg treatment (tx) for ≤3 cycles q3w or nivo 360mg + nab-paclitaxel 185mg/m2 (d1, d8) + carboplatin AUC5 for ≤3 cycles q3w based on PD-L1 status. Primary endpoint was major pathological response (MPR: ≤10% viable tumor cells). Key secondary endpoints included pathologic complete response (pCR), objective response rate (ORR, RECIST v1.1), adverse events (AEs) including treatment-related (TRAE) and immune-related (irAE). We correlated PD-L1 status and perioperative ctDNA presence with pCR and event-free survival (EFS).
Results
From 08/08/2019 to 08/16/2021 52 pts were accrued and 46 had surgery (surg outcome in the table). The pre-surg ORR was 51.9% (27/52) with 2 CR. 25/46 (54.3%) achieved MPR of which 13 (28.3%) were pCR. In PD-L1 ≥ 50% group mono-nivo achieved 18.2% MPR while chemoimmunotherapy achieved 80%. AEs occurred in all pts during NA tx, including irAEs in 36/52 (69.2%) and 3 pts discontinued NA tx. 45 (97.8%) pts had sufficient tissue for tumor-informed MRD. MRD was detected in 84.4% in pre-NA (n=38), 91.1% in post-NA (n=41) and 80.0% in post-surg samples (n=36). Significant ctDNA clearance post-NA was seen in pts with pCR vs non- pCR (OR=8.56, 95% CI: 1.22-Inf, p=0.03). With a median follow-up of 25.1 months (95% CI: 22.4-27.7m), 2yr-EFS rate for pts with MRD– (both post-NA and -surg) vs. MRD+ (either post-NA or -surg) was 86.6% vs 47.3% (HR, 0.20; 95% CI: 0.04, 0.94; p=0.02).
Parameter A1 A2 B1 B2 Sum Enrolled 12 12 16 12 52 PD-L1 ≥ 50% ≥ 50% 1-49% ≤ 1% Regimen Mono-nivo Combination Combination Combination No surg 1 2 1 1 6 PD irAE irAE 1 Declined 1 PD Delayed surg < 2w 3 0 1 1 Median week from last NA to surg 4 5 5 5 R0 11 10 14 11 46 Minimally invasive (MI) 11 (23.9) 9 (19.6) 13 (28.3) 11 (23.9) 44 (95.7) MI to thoracotomy 0 1 1 0 2 (4.3) Lobectomy 10 (21.7) 6 (13.0) 12 (26.1) 11 (23.9) 37 (80.4) Pneumonectomy 0 1 1 0 2 (4.3) Other 1 3 1 0 5 Lymph node Downstaging 4 (8.7) 7 (15.2) 7 (15.2) 8 (17.4) 26 (56.5) pCR (%) 18.2 50.0 21.4 27.3 MPR (%) 18.2 80.0 64.3 54.5 Pre-NA (+) 5 (14.7) 9 (26.5) 11 (32.3) 9 (26.5) 34 ctDNA clearance (%) 14.3 77.8 69.2 66.7 Post-surg (-) 4 (14.3) 8 (28.6) 11 (39.3) 5 (17.8) 28
Conclusions
We prefer chemoimmunotherapy as neoadjuvant treatment regardless of PD-L1 expression. ctDNA clearance would be a predictor of favorable pathological and survival outcomes.
Clinical trial identification
NCT04015778.
Legal entity responsible for the study
Chinese Thoracic Oncology Group, CTONG.
Funding
Bristol Myers Squibb.
Disclosure
W. Zhong: Non-Financial Interests, Personal, Board Member in the Educational Committee (mainly participated in educational event organization): International Association for the Study of Lung Cancer (IASLC). Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi, Yunhan; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). All other authors have declared no conflicts of interest.