Founded in 1964, the American Society of Clinical Oncology (ASCO) is the world's leading professional organization for physicians, researchers and specialists in the field of oncology.
Major annual event for clinical research and innovation in oncology, the ASCO International Conference is held every year in Chicago. Several tens of thousands of international specialists meet there to present research that aimed at improving treatment standards and patient care. https://conferences.asco.org/
For the 2025 edition, our team was involved in the following studies:
Maintenance with OSE2101 plus FOLFIRI vs FOLFIRI alone after FOLFIRINOX (FFX) induction in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC): Primary endpoint results of a randomized TEDOPAM GERCOR D17-01 PRODIGE 63 trial.
Authors: Anthony Turpin, Emmanuel Mitry, Olivier Bouche, Yves Rinaldi, Christophe Borg, Jean-Philippe Metges, Gael Roth, Thierry Lecomte, Christophe Tournigand, Isabelle Trouilloud, You Heng Lam, Clélia Coutzac, François Ghiringhelli, Christophe Louvet, Vincent Hautefeuille, Aurélien Lambert, Marielle Guillet, Marie-Line Garcia-Larnicol, Julie Henriques, Cindy Neuzillet
Background:
OSE2101 is an off the shelf vaccine made of 10 synthetic HLA-A2-restricted peptides targeting 5 tumor associated antigens. This multicenter, randomized, non-comparative, phase II study assessed FOLFIRI ± OSE2101 maintenance in aPDAC Pts without progression after 8 cycles of FFX.
Methods:
Eligible aPDAC Pts were randomized to FOLFIRI (Arm A) or FOLFIRI + OSE2101 (Arm B: subcutaneous injection on D1, D15, Q4W/6 doses then Q8W to M12 then Q12W up to M24). Stratification factors: tumor stage (locally advanced vs metastatic), best response to FFX (partial or complete response [CR, PR] vs stable disease [SD]), and center. Primary endpoint: overall survival (OS) rate at M12 in evaluable Pts (M12-OS; Fleming 2-stage design, H0: 25%; H1: 50%, 1-sided alpha: 2.5%, power: 90%); secondary endpoints: progression-free survival (PFS; RECIST v1.1), best response, duration of disease control (DDC), and safety.
Results:
107 Pts (ITT) were randomized (53/Arm A, 54/Arm B) between 04/2021 and 05/2023. Median age 64 years (range:37-81), 53% men, 69% had metastases, 36%/64% had PR/SD to prior FFX. No evidence of imbalance in Pt characteristics was observed between arms. Median number of OSE2101 injections was 7.5 (1-14). Median treatment duration of FOLFIRI was 5.4 months in both arms. At data cut-off (Dec 9, 2024), median follow-up was 21.4 months with 101 evaluable Pts for M12-OS (49/Arm A, 52/Arm B; 4 consent withdrawals, 1 Pt’s decision, 1 treatment interruption >4 weeks). Number of death events (n/%) was 19/35.8% in Arm A and 18/33.3% in Arm B. M12-OS (95%CI) was 61% (46.2%-74.8%) in Arm A and 65% (50.9%-78.0%) in Arm B. Median (95%CI) OS and PFS (ITT) were 17.3 months (10.6–23.2) and 8.2 months (5.3–11.6) in Arm A, and 15.5 months (12.4–19.3) and 7.8 months (5.4–10.6) in Arm B. Other secondary endpoints are described in Table. Among 33 Pts with SD to prior FFX in Arm B, 6 (18%) had CR/PR (1/5) when adding OSE2101 to FOLFIRI vs 5 (no CR) among 35 Pts in Arm A. In the safety population, 7 SAEs/6 Pts (12%) in Arm A and 22 SAEs/14 Pts (26%) in Arm B were reported. No unexpected SAEs were observed with OSE2101 except 1 inappropriate administration, and no evidence of increased toxicity of FOLFIRI with OSE2101.
Conclusions:
TEDOPAM met its primary objective with minimal toxicity and positive outcomes of adding OSE2101 cancer vaccine to maintenance FOLFIRI, albeit mitigated by unexpectedly favorable OS in the control arm. Two complete responses were observed when adding OSE2101. Further follow-up is ongoing and translational analysis planned.
ITT | Arm A N=53 | Arm B N=54 |
Best response, n (%) | | |
CR | 0 (0.0) | 2 (3.7) |
PR | 12 (22.6) | 10 (18.5) |
SD | 28 (52.8) | 34 (63.0) |
Progressive disease (PD) | 8 (15.1) | 8 (14.8) |
Missing | 5 (9.5) | 0 (0.0) |
DC rate, n (%) | 40 (75.5) | 46 (85.2) |
DDC (95% Cl) | 8.8 (6.2-12.9) | 9.8 (6.8-14.8) |
A phase II study of an anti-telomerase CD4+ T-helper vaccine (UCPVax) with or without temozolomide in newly diagnosed glioblastoma.
Authors: Antoine Carpentier, Stefania Cuzzubbo, Aurelia Meurisse, Clotilde Verlut, Jean David Fumet, Laura Boullerot, Charlotte Bronnimann, Emmeline Tabouret, Renata Ursu, Claudia Barsan, Catherine Belin, Alice Hervieu, Marion Jacquin, Melanie Moltenis, Anne-Laure Clairet, Christine Fagnoni-Legat, François Ghiringhelli, Dewi Vernerey, Caroline Laheurte, Olivier Adotevi
Background:
UCPVax is a therapeutic vaccine designed to stimulate CD4+ helper T cell responses against telomerase (TERT), a protein highly expressed in glioblastoma (GBM). Temozolomide (TMZ), a standard chemotherapeutic agent in the treatment of GBM, has been shown to induce CD4+ T-cell lymphopenia, which could potentially impair the immune response to the vaccine. We conducted a multicenter, 2-cohort, phase IIa study to evaluate the immunogenicity and efficacy of UCPVax, with or without TMZ, as adjuvant therapy in patients with newly diagnosed GBM following chemoradiation.
Methods:
Patients with non-mutated IDH1 glioblastoma (GBM) were enrolled one month after completing concurrent radiotherapy and temozolomide (TMZ). Cohort A received the vaccine alone, without additional TMZ, while Cohort B was treated with both the vaccine and six monthly cycles of TMZ. The primary endpoint was the induction of TERT-specific CD4+ T cell responses, assessed ex vivo using the INF-γ ELISpot assay. Secondary endpoints included epitope spreading, clinical outcomes, and safety.
Results:
Thirty-one GBM patients with unmethylated MGMT status were included in cohort A, and 30 patients (50% with unmethylated MGMT status) were included in cohort B. The vaccine was well tolerated, with no vaccine-related serious adverse events. Vaccine-expanded TERT-specific CD4+ T cells were detectable ex vivo in 25/30 (83%) of patients in cohort A (no additional TMZ) and in 18/26 69% of patients in cohort B (treated with additional TMZ). Epitope spreading was induced in 29 out of 55 evaluable patients (52.7%), corresponding to 15/26 (57.7%) in cohort A and 14/29 (48%) in cohort B. Median overall survival (OS) was significantly improved in patients who developed an epitope spread response compared to those who did not (19.3 vs. 12.8 months, P = 0.03). In the 44 patients with measurable disease at the time of inclusion, the radiological response rate (RR) was 34%, including minor responses. In patients who developed epitope spreading after vaccination (n = 22), the RR was 50%, compared to 18.7% in patients without epitope spreading (P = 0.05). Furthermore, tumor-infiltrating lymphocytes against TERT were detected in 3 vaccinated patients who underwent surgery at recurrence.
Conclusions:
UCPVax demonstrated robust immunogenicity, even when co-administered with TMZ, and was associated with improved overall survival (OS) in GBM patients who developed an epitope spreading response. These findings support further clinical investigation of TERT-derived CD4+ helper vaccine in GBM patients.
About Sophie PAGET-BAILLY
Sophie Paget-Bailly is a research engineer in epidemiology and clinical research. She passed with honours the East of France inter-region master’s degree in public health and occupational and environmental risks. During the master’s degree’s internship in the Interregional Epidemiology Unit of Bourgogne/Franche-Comté, she realized a quantitative health risk assessment in the context of chemical contamination of groundwater. She defended a PhD in Public Health and Epidemiology in Paris XI University, Doctoral School 420, working in the Centre for Research in Epidemiology and Population Health in Villejuif, France. Her PhD research focused on occupational exposures and head and neck cancer.