Abstract 2536
Background
TG4001 is a vaccine targeting HPV E6 and E7. It has shown to provide histological clearance of cervical pre-cancerous lesions (Harper DM et al. 2019). We aimed to evaluate in the Ph Ib part the safety of TG4001 in combination with avelumab in HPV 16-positive cancers (NCT03260023).
Methods
Patients with HPV-16 positive cancers who had received ≤ 2 prior regimens for R/M disease were enrolled to either one of the two doses of the vaccine (5x106 and 5x107 pfu). TG4001 was administered SC weekly for 6 weeks, every 2 weeks up to M6, and every 12 weeks thereafter. Avelumab was given IV at 10mg/kg every 2 weeks. Tumor response was assessed by RECIST 1.1. For translational and immunological assessments, PBMC samples were collected longitudinally and tissue samples were collected at baseline and D43.
Results
Nine patients with oropharyngeal (5), anal (2), cervical (1) or vaginal (1) cancer, were enrolled in this trial, 3 patients on the low dose and 6 patients on the high dose of TG4001. No dose-limiting toxicity and no SAE have been observed. 3 patients had a confirmed partial response according to RECIST1.1. 3/5 evaluable patients for T-cell response by ELISPOT displayed detectable peripheric responses against E6 and/or E7 after treatment, and an overall trend to decreased circulating regulatory T cells (Treg). At the tissue level, 4/5 evaluable patients showed an increase of CD8 infiltration and/or a decrease in infiltrated Treg/CD8 ratio at day 43. The percentage of PD-L1+ cells doubled in all low or moderate expressors. The phenotypic findings were supported by increased expression of genes associated with both adaptive and innate immunity and with a shift from a “cold” tumor to a “hot” tumor gene signature.
Conclusions
The combination of TG4001 and avelumab is safe and provides anti-tumor activity in HPV-16+ cancer patients. The treatment induces immune changes in patients with poor baseline immune contexture. The combination is being evaluated in the ongoing Ph II part.
Clinical trial identification
NCT03260023.
Editorial acknowledgement
Legal entity responsible for the study
Transgene SA.
Funding
Transgene.
Disclosure
C. Le Tourneau: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: GSK. J. Delord: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Research grant / Funding (institution): MSD; Advisory / Consultancy: EMD Serono; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): AstraZeneca. P. Cassier: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Research grant / Funding (institution): Blueprint Medicines; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Research grant / Funding (institution): Taiho Pharmaceuticals; Research grant / Funding (institution): Toray Industries; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Innate Pharma; Research grant / Funding (institution): Janssen. D. Loirat: Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD. A. Tavernaro: Full / Part-time employment: Transgene SA. B. Bastien: Full / Part-time employment, Employed by sponsor of the study: Transgene SA. K. Bendjama: Shareholder / Stockholder / Stock options, Full / Part-time employment: Transgene.
Resources from the same session
2507 - KEYLYNK-010: Phase 3 Study of Pembrolizumab (pembro) Plus Olaparib (OLA) vs Enzalutamide (ENZA) or Abiraterone (ABI) in ENZA- or ABI-Pretreated Patients (pts) With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Had Progression on Chemotherapy (CTx)
Presenter: Evan Yu
Session: Poster Display session 3
Resources:
Abstract
2944 - PROSTRATEGY: A Spanish Genitourinary Oncology Group (SOGUG) multi-arm multistage (MAMS) phase III trial of immunotherapy strategies in high-volume metastasic hormone-sensitive prostate cancer.
Presenter: Jose Arranz Arija
Session: Poster Display session 3
Resources:
Abstract
3535 - A phase 1 study of AMG 160, a half-life extended bispecific T cell engager (HLE BiTE) immuno-oncology therapy targeting PSMA, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Ben Tran
Session: Poster Display session 3
Resources:
Abstract
4951 - ProBio: An outcome-adaptive, multi-arm, open-label, multiple assignment randomised controlled biomarker-driven trial in patients with metastatic castration-resistant prostate cancer (EudraCT: 2018-002350-78, NCT03903835)
Presenter: Johan Lindberg
Session: Poster Display session 3
Resources:
Abstract
2892 - A phase 3 randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (NCT03748641)
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
2427 - The Extended/Phase II Study of Safety And Tolerability Of Proxalutamide (GT0918) In Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Who Failed Either Abiraterone (Abi) Or Enzalutamide (Enza)
Presenter: Nicholas Vogelzang
Session: Poster Display session 3
Resources:
Abstract
3224 - Addition of an oral docetaxel treatment (ModraDoc006/r) to androgen deprivation therapy (ADT) and intensity-modulated radiation therapy (IMRT) in patients with high risk N+M0 prostate cancer
Presenter: Marit Vermunt
Session: Poster Display session 3
Resources:
Abstract
3312 - A phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy with LHRH agonist or antagonist versus anti-androgen therapy with apalutamide in patients with biochemical progression after radical prostatectomy.
Presenter: Piet Dirix
Session: Poster Display session 3
Resources:
Abstract
2829 - Health-Related Quality of Life (HRQoL) and Updated Follow-Up From KEYNOTE-057: Phase 2 Study of Pembrolizumab (pembro) for Patients (pts) With High-Risk (HR) Non–Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guérin (BCG)
Presenter: Ronald de Wit
Session: Poster Display session 3
Resources:
Abstract
2673 - Clinical activity of vofatamab (V), an FGFR3 selective antibody in combination with pembrolizumab (P) in metastatic urothelial carcinoma (mUC), updated interim analysis of FIERCE-22
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract