Table 1.
Clinical Trials of Personalized Therapeutic Cancer Vaccines
| NCT No., Patients Expected (Trial Status): ClinicalTrials.gov | Sponsors | Antigen Platform | Antigen Selection Algorithm | Delivery | Dose and Schedule | Indication | Combination Therapy | Biomarkers | Endpoints | References |
|---|---|---|---|---|---|---|---|---|---|---|
| NCT03289962, n = 770 (phase 1 recruiting, 2020 completion) | BioNTech and Genentech | neoantigen mRNA | MHC class I & II prediction, mutations ranked by HLA allele-specific antigen binding affinity | i.v. infusion RNA-lipoplex, size and charge optimized | 25–100 μg qw prime + boosters | multiple solid tumors | atezolizumab | IFN-γ ELISPOT, flow cytometry, TCR analysis, T cell killing | AEs, imAEs, DLTs, ORR, DOR, PFS, OS | 60 |
| NCT03815058, n = 132 (phase 2 recruiting, 2022 completion) | BioNTech and Genentech | neoantigen mRNA | ˆ | ˆ | not specified; qw prime + boosters | melanoma | pembrolizumab | ˆ | AEs, ORR DOR, PFS, OS | 61 |
| NCT03313778, n = 90 (phase 1 recruiting, 2021 completion) | Moderna and Merck | neoantigen mRNA | based on HLA type; analyzes IEDB data for immunogenicity prediction | intramuscular via lipid nanoparticles | 40–1, 000 μg nine q3w cycles | multiple solid tumors | pembrolizumab | neoantigen-specific T cell response | AEs, DLTs, RFS, DOR, PFS, OS | 62 |
| NCT03897881, n = 150 (phase 2 recruiting, 2023 completion) | Moderna and Merck | neoantigen mRNA | ˆ | ˆ | 1,000 μg nine q3w cycles | melanoma | pembrolizumab | ˆ | AEs, RFS, DMFS, OS | 63 |
| NCT03948763, n = 100 (phase 1 recruiting, 2024 completion) | Moderna and Merck | TAAs mRNA | targets four most prevalent KRAS mutations | ˆ | not specified | CRC, NSCLC, pancreatic | pembrolizumab | T cell receptor clonality and diversity | AEs, DLTs, discontinuation, ORR | 64,65 |
| NCT03380871, n = 15 (phase 1 active, not recruiting, 2021 completion) | Neon Therapeutics and Merck | neoantigen peptides | Recon bioinformatics engine quantifies epitope quality from mass spectrometry binding to predict peptide presentation | subcutaneous (up to four sites) with poly(ICLC) | 5 priming doses then qw + boosters | NSCLC | pembrolizumab, pemetrexed, carboplatin | IFN-γ ELISPOT, T cell phenotyping | AEs, SAEs, ORR, DOR, RCR, CBR, PFS, OS | 66 |
| NCT02897765, n = 55 (phase 1 active not recruiting, 2020 completion) | Neon Therapeutics and BMS | neoantigen peptides | ˆ | ˆ | not specified | multiple solid tumors | nivolumab | IFN-γ ELISPOT, cytokines, flow cytometry | AEs, SAEs, ORR, DOR, RCR, CBR, PFS, OS | 67 and P.A. Ott et al., 2019, Soc. Immunother. Cancer, conference |
| NCT03639714, n = 214 (phase 1/2 recruiting, 2022 completion) | Gritstone Oncology and BMS | neoantigen adenovirus vector + self-amplifying mRNA | Edge, novel AI model for antigen prediction for optimal immunogenicity/T cell recognition | intramuscular via viral vector | ChAdV prime 1 × 1012 vp SAM boosts 30–300 μg | NSCLC, MSS-CRC, EC, BC | nivolumab ipilimumab | ex vivo ELISPOT | AEs, immune response, ORR, DOR, CBR, PFS, OS | 68 |
| NCT03953235, n = 144 (phase 1/2 recruiting, 2023 completion) | Gritstone Oncology and BMS | neoantigen tumor-specific shared neoantigen peptides | ˆ | ˆ | not specified | NSCLC, CRC, pancreatic, other solid tumors | ˆ | ex vivo ELISPOT | ˆ | 69,70 |
| NCT02992977, n = 5 (phase 1 terminated in 2019) | Agenus | neoantigen peptides linked to heat shock protein | AIM algorithm for ID and immunogenicity prediction in vitro mass spectrometry validation | subcutaneous peptides are linked to recombinant HSP70 protein carrier + QS-21 Stimulon adjuvant | 30–240 μg of AutoSynVax + 50 μg of QS adjuvant q2w up to 1 year | melanoma, NSCLC, bladder, TNBC, RCC, HNC, CRC, solid tumors | none | ELISPOT, cytokines | AEs, T cell response, ORR, PFS, OS | 71 |
| NCT03673020, n = 3 (phase 1 recruiting, 2020 completion) | Agenus | neoantigen peptides linked to heat shock protein | ˆ | ˆ | 50 μg + 240 μg of Hsc70 + 50 μg of QS q2w | multiple solid tumors | none | ˆ | AEs. time of recurrence | 71 |
| NCT03633110, n = 99 (phase 1/2 recruiting, 2022 completion) | Genocea | neoantigen peptides | Atlas proprietary system, ex vivo assay for ID, epitope prediction based on predicted binding to HLA | subcutaneous with Hiltonol poly(ICLC) adjuvant | not specified; days 1, 22, and 43 with boosters at weeks 12 and 24 | melanoma, NSCLC, RCC, HNC, UC | nivolumab or pembrolizumab | IFN-γ ELISPOT, cytokines, immuno-phenotyping | anti-tumor activity | 72 |
| NCT03265080, n = 5 (phase 1 active not recruiting, 2020 completion) | Advaxis Immunotherapies and Amgen | neoantigen Listeria monocytogenes- secreting TAAs | MINE system, machine learning to predict and weigh rankings, allele frequency, tumor drivers, MHC binding | i.v. infusion −15 min attenuated bacterial vector + adjuvant fusion protein tLLO-NEO | 1 × 108–1 x 109 CFU, q3w for 2 years | NSCLC, MSS-CRC, HNC, UC | pembrolizumab | ELISPOT, cytokines | AEs, ORR, DOR, DCR, PFS, OS | 73 |
| NCT03847519, n = 74 (phase 1/2 recruiting, 2023 completion) | Advaxis Immunotherapies and Personalis | TAAs (public or shared hotspots) Listeria monocytogenes secreting TAA | ˆ + ImmunoID NeXT deep analysis platform | ˆ | ˆ | NSCLC | pembrolizumab | ELISPOT, cytokines, gene expression, immuno-sequencing of T cell repertoire | AEs, anti-tumor activity, PFS, OS | 74 |
| NCT02325557, n = 51 (phase 1/2 completed 2018) | Advaxis Immunotherapies and Merck | TAAs Listeria monocytogenes-secreting TAAs | MINE system with machine learning to predict and weigh rankings, allele frequency, tumor drivers, MHC binding | ˆ | 1 x 109–1 × 1010 CFU q3w for 2 years | prostate | pembrolizumab | ELISPOT, gene expression, flow cytometry, TCR sequencing | AEs, immune responses, PSA, anti-tumor activity, PFS, PROs | 75 |
| NCT03189030, n = 28 (phase 1 active, not recruiting, 2020 completion) | Aduro Biotech | TAAs Listeria monocytogenes- secreting TAAs | ZoomX workflow for neoantigen ID and selection | i.v. infusion −1 h with live attenuated Listeria monocytogenes | 1 × 108–1 × 109 CFU q3w 17 injections per year | MSS-CRC | none | IFN-γ ELISPOT | AEs | 76 |
| NCT01675765, n = 60 (phase 1completed 2019) | Aduro Biotech | TAAs Listeria monocytogenes- secreting TAAs | ˆ | ˆ | 1 × 109 CFU two infusions q2w apart followed by two boosts q3w | malignant pleural mesothelioma | pemetrexed, cisplatin | IFN-γ ELISPOT, flow cytometry | AEs, immune responses, serum mesothelin, ORR, TTP, OS | 77 |
| NCT03548467, n = 65 (phase 1/2 recruiting, 2023 completion) | Vaccibody and Nektar- Therapeutic | neoantigen DNA plasmid | NeoSELECT neoepitope selection for high-frequency, high-quality neoepitopes | intramuscular needle-free jet injection DNA plasmid pUMVC4a vector | 3 mg of multiple dose induction q4w until week 50, 14 injections | melanoma NSCLC, RCC, UC, SCCHN | bempegaldesleukin | IFN-γ ELISPOT, flow cytometry | AEs, immune responses, ORR, DOR, PFS | J. Krauss et al., 2019, Soc. Immunother. Cancer, conference |
| NCT03552718, n = 16 (phase 1 recruiting, 2020 completion) | NantBioscience | neoantigen yeast based | not specified | injectable suspension recombinant yeast-based vector | not specified | CRC, BC, HNC, NSCLC, pancreatic, liver | none | not specified | AEs, RR, DFS, PFS, OS | 78,79 |
| NCT03164772, n = 56 (phase 1/2 recruiting, 2024 completion) | CureVac, Boehringer Ingelheim, and MedImmune | neoantigen mRNA | MutSig algorithm and sparse partial correlation estimation algorithm | intradermal injection needle-free lipid nanoparticles | 2 × 200 μL as six components, total of 14 doses in 12 cycles | NSCLC | durvalumab, tremelumumab | ELISPOT, flow cytometry, cytokines, CD8+ T cell response | AEs, ORR, DOR, PFS, OS | 80 |
| NCT03199040, n = 24 (phase 1 recruiting, 2022 completion) | MedImmune and Washington University St. Louis | neoantigen DNA | public tools, including NetMHC, NetMHCpan, and NetChop algorithms to predict binding and epitope processing | intramuscular electroporation administration delivery system with two injections at separate sites | not specified; D1, D29, D57, D85, D113, D141 q3w between injections | TNBC | durvalumab | ELISPOT, flow cytometry | AEs, immune responses | 81 |
| NCT03598816, n = 48 (phase 2 not yet recruiting 2022 completion) | MedImmune and Washington University St. Louis | neoantigen DNA | ˆ | intramuscular electroporation administration delivery system one injection into each deltoid or lateralis, two injections at each vaccination | not specified; C1D1, C1D15, C2D1, C3D1, C4D1, and C5D1 total of six doses with two injections per dose | RCC | durvalumab, tremelumumab | ELISPOT, tetramer staining | AEs, ORR, PFS, OS | 81 |
| NCT02933073, n = 15 (phase 1 recruiting, 2026 completion) | Truvax and University of Connecticut | neoantigen peptides | Epi-Seq pipeline and differential agretopic index to rank epitopes by MHC score differences | not specified | not specified; six injections monthly for 6 months | ovarian | none | immune responses, CD8+ T cell proliferation and phenotyping | AEs, immune responses | 82,83 |
Information was obtained from public documents (scientific literature, posters, patents, and/or corporate presentations); ˆ indicates the same finding as the prior row. AE, adverse event; AI, artificial intelligence; BC, breast cancer; CBR, clinical benefit rate; CFU, colony-forming units; ChAdV chimpanzee adenoviral vector; CRC, colorectal cancer; DCR, disease control rate; DFS, disease-free survival; DLT, dose-limiting toxicity; DMFS, distant metastasis-free survival; DOR, duration of response; EC, endometrial cancer; ELISPOT, enzyme-linked immunospot; HLA, human leukocyte antigen; HNC, head and neck cancer; IEDB, Immune Epitope Database and Analysis Resource; IFN-γ, interferon γ; imAE, immune-mediated adverse event; i.v., intravenous; MHC, major histocompatibility complex; mRNA, messenger RNA; MSS, microsatellite stable; NSCLC, non-small-cell lung cancer; ORR, objective response rate; OS, overall survival; poly(ICLC), carboxymethylcellulose polyinosinic-polycytidylic acid, and poly-l-lysine double-stranded RNA; PFS, progression-free survival; PSA, prostate-specific antigen; PRO, patient reported outcomes; qw, once weekly; q2w, every 2 weeks; q3w, every three weeks; RCC, renal cell carcinoma; RCR, radiologic complete response; RFS relapse-free survival; RP2D, recommended phase 2 dose; RR, relapse rate; SAE, serious adverse event; SAM self-amplifying; SCCHN, squamous cell carcinoma of the head and neck; TAA, tumor-associated antigen; TCR, T cell receptor; TNBC, triple-negative breast cancer; TTP, time to progression; UC, urothelial cancer; VP, viral particles.