(1) Mørk SK (2) Skadborg SK (3) Albieri B (4) Draghi A (5) Bol K (6) Kadivar M (7) Westergaard MCW (8) Stoltenborg Granh¿j J (9) Borch A (10) Petersen NV (11) Thuesen N (12) Rasmussen IS (13) Andreasen LV (14) Dohn RB (15) Yde CW (16) Noergaard N (17) Lorentzen T (18) Soerensen AB (19) Kleine-Kohlbrecher D (20) Jespersen A (21) Christensen D (22) Kringelum J (23) Donia M (24) Hadrup SR (25) Marie Svane I
Mørk et al. report the feasibility, safety, efficacy, and immunogenicity of the dose-escalation phase of a personalized neoantigen vaccine, EVX-01-CAF09b, in addition to anti-PD-1 therapy in patients with metastatic melanoma. The combination was safe, well tolerated, and capable of eliciting T cell responses, without vaccine-related serious adverse events. Vaccine neoantigen-specific CD4+ and CD8+ T cell responses were elicited at all dose levels, and objective tumor responses were observed in 66% of patients. The number of immunogenic peptides and PIONEER epitope quality scores were predictive of clinical responses and longer PFS.
Contributed by Shishir Pant
(1) Mørk SK (2) Skadborg SK (3) Albieri B (4) Draghi A (5) Bol K (6) Kadivar M (7) Westergaard MCW (8) Stoltenborg Granh¿j J (9) Borch A (10) Petersen NV (11) Thuesen N (12) Rasmussen IS (13) Andreasen LV (14) Dohn RB (15) Yde CW (16) Noergaard N (17) Lorentzen T (18) Soerensen AB (19) Kleine-Kohlbrecher D (20) Jespersen A (21) Christensen D (22) Kringelum J (23) Donia M (24) Hadrup SR (25) Marie Svane I
Mørk et al. report the feasibility, safety, efficacy, and immunogenicity of the dose-escalation phase of a personalized neoantigen vaccine, EVX-01-CAF09b, in addition to anti-PD-1 therapy in patients with metastatic melanoma. The combination was safe, well tolerated, and capable of eliciting T cell responses, without vaccine-related serious adverse events. Vaccine neoantigen-specific CD4+ and CD8+ T cell responses were elicited at all dose levels, and objective tumor responses were observed in 66% of patients. The number of immunogenic peptides and PIONEER epitope quality scores were predictive of clinical responses and longer PFS.
Contributed by Shishir Pant
BACKGROUND: Neoantigens can serve as targets for T cell-mediated antitumor immunity via personalized neopeptide vaccines. Interim data from our clinical study NCT03715985 showed that the personalized peptide-based neoantigen vaccine EVX-01, formulated in the liposomal adjuvant, CAF09b, was safe and able to elicit EVX-01-specific T cell responses in patients with metastatic melanoma. Here, we present results from the dose-escalation part of the study, evaluating the feasibility, safety, efficacy, and immunogenicity of EVX-01 in addition to anti-PD-1 therapy. METHODS: Patients with metastatic melanoma on anti-PD-1 therapy were treated in three cohorts with increasing vaccine dosages (twofold and fourfold). Tumor-derived neoantigens were selected by the AI platform PIONEER and used in personalized therapeutic cancer peptide vaccines EVX-01. Vaccines were administered at 2-week intervals for a total of three intraperitoneal and three intramuscular injections. The study's primary endpoint was safety and tolerability. Additional endpoints were immunological responses, survival, and objective response rates. RESULTS: Compared with the base dose level previously reported, no new vaccine-related serious adverse events were observed during dose escalation of EVX-01 in combination with an anti-PD-1 agent given according to local guidelines. Two patients at the third dose level (fourfold dose) developed grade 3 toxicity, most likely related to pembrolizumab. Overall, 8 out of the 12 patients had objective clinical responses (6 partial response (PR) and 2 CR), with all 4 patients at the highest dose level having a CR (1 CR, 3 PR). EVX-01 induced peptide-specific CD4+ and/or CD8+T cell responses in all treated patients, with CD4+T cells as the dominating responses. The magnitude of immune responses measured by IFN-_ ELISpot assay correlated with individual peptide doses. A significant correlation between the PIONEER quality score and induced T cell immunogenicity was detected, while better CRs correlated with both the number of immunogenic EVX-01 peptides and the PIONEER quality score. CONCLUSION: Immunization with EVX-01-CAF09b in addition to anti-PD-1 therapy was shown to be safe and well tolerated and elicit vaccine neoantigen-specific CD4+and CD8+ T cell responses at all dose levels. In addition, objective tumor responses were observed in 67% of patients. The results encourage further assessment of the antitumor efficacy of EVX-01 in combination with anti-PD-1 therapy.
Author Info: (1) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark sofie.kirial.moerk@regionh.dk. (2) Department of He
Author Info: (1) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark sofie.kirial.moerk@regionh.dk. (2) Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark. (3) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark. (4) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark. (5) Medical Oncology, Radboudumc, Nijmegen, The Netherlands. (6) Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark. (7) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark. (8) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark. (9) Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark. (10) Evaxion Biotech, Copenhagen, Denmark. (11) Evaxion Biotech, Copenhagen, Denmark. (12) Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. (13) Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. (14) Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. (15) Genomic Medicine, Rigshospitalet, Copenhagen, Denmark. (16) Department of Urology, Copenhagen University Hospital, Herlev, Denmark. (17) Department of Gastroenterology, Copenhagen University Hospital, Herlev, Denmark. (18) Evaxion Biotech, Copenhagen, Denmark. (19) Evaxion Biotech, Copenhagen, Denmark. (20) Evaxion Biotech, Copenhagen, Denmark. (21) Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. (22) Evaxion Biotech, Copenhagen, Denmark. (23) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark. (24) Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark. (25) Department of Oncology, Copenhagen University Hospital, National Center for Cancer Immune Therapy (CCIT-DK), Herlev, Denmark.
Citation: J Immunother Cancer 2024 May 23 12: Epub05/23/2024