Table 2.
Summary of study details of included studies. Full-text articles are marked with asterisks. All data, except safety, are presented for TNBC cohort of each trial.
| Vaccine Name | Study | # Patients (VG 1:CG 2) | Dosing, Route, Intervals | Follow-up Duration (m 3/w 4/d 5) | Key Observations (Efficacy) | Key Observations (Safety) |
|---|---|---|---|---|---|---|
| AE37 | Brown et al., 2020 * | 45 (21:24) | AE37 (500 µg) + GM-CSF (125 µg), x6 q3-4w (VG)/ GM-CSF (125 µg) x6 q3-4w (CG) ID 6 4 boosters q6m |
59.9 m | No statistically significant difference in 5-y 7 DFS 8 (p = 0.226, HR 9 = 0.443); signs of DFS improvement for advanced-stage TNBC patients (p = 0.078, HR = 0.184) |
Safe and well-tolerated, majority of AE 10s of grade 1, no >grade 3 toxicities |
| Peace et al., 2017 | 42 (21:21) | 55 m | Statistically significant difference in DFS (p = 0.0478, HR = 0.26) | Safe and well-tolerated, no >grade 3 AEs | ||
| Peace et al., 2017 | N/S | 46.7 m | Signs of DFS improvement for advanced-stage TNBC patients (p = 0.054) | N/S 11 | ||
| Mittendorf et al., 2016 * | 50 (25:25) | 25 m | No statistically significant difference in 5-y DFS (p = 0.12, HR = 0.403) | Maximum local AEs grade 1/2, no >grade 3 systemic AEs | ||
| Greene et al., 2015 | 51 (25:26) | N/S | No statistically significant difference in 5-y DFS (p = 0.65, HR = 0.42) | N/S | ||
| Mittendorf et al., 2014 | 50 (25:25) | N/S | No statistically significant difference in 5-y DFS (p = 0.12, HR = 0.40) | Safe and well-tolerated, no grade 3 local AEs, 1 pt 12 had grade 3 systemic AE | ||
| Mittendorf et al., 2012 | 36 (13:23) | 22.3 m | No statistically significant difference in 5-y DFS (p = 0.23) | N/S | ||
| GP2 | Brown et al., 2020 * | N/S | GP2 (500 µg) + GM-CSF (125 µg), x6 q3-4w (VG)/ GM-CSF (125 µg), x6 q3-4w (CG) ID 4 boosters q6m |
41.7 m | No statistically significant difference in RR 13 (HR~1.42) | Safe and well-tolerated, majority of AESs of grade 1, no >grade 3 AEs |
| Trappey et al., 2013 | N/S | 24 m | No statistically significant difference in RR (p = 0.251) | Maximum local and systemic AEs similar between groups, no grade 3 systemic AEs | ||
| Nelipepimut-S | Chick et al., 2021 * | 99 (55:44) | trastuzumab (LD 14 8mg/kg, MD 15 6 mg/kg) q3w for 1 y + NPS (1000 µg) + GM-CSF (250 µg), x6 q3w, starting with 3rd trastuzumab dose (VG)/ trastuzumab (LD 8mg/kg, MD 6 mg/kg) q3w for 1 y + GM-CSF (250 µg), x6 q3w, starting with 3rd trastuzumab dose (CG) ID 4 boosters q6m |
36 m | Statistically significant differences in 36-m DFS of total pts (p = 0.01, HR = 0.25), HER2 IHC 16 1+ pts (p = 0.01, HR = 0.17), HLA-A24+ pts (p < 0.01, HR = 0.08), pts with prior NAC 17 (p < 0.01, HR = 0.21) | N/S |
| Clifton et al., 2020 * | 97 (53:44) | 26.1 m | Statistically significant difference in 24-m DFS (p = 0.01, HR = 0.25) | Safe and well-tolerated, no added cardiac or overall AEs, no grade 4/5 AEs | ||
| Clifton et al., 2019 | 97 (53:44) | N/S | Statistically significant difference in 36-m DFS of pts (p = 0.013, HR = 0.262), pts with prior NAC (p = 0.013, HR= 0.226), HER2 IHC 1+ pts (p= 0.014, HR= 0.178), ≥51 y-old pts (p= 0.004, HR= 0.144), stage I/II pts (p = 0.006) | N/S | ||
| Hickerson et al., 2019 | N/S | 25.7 m | Statistically significant difference in 24-m DFS (p = 0.013, HR = 0.26) | Safe, no added cardiac or overall AEs, no grade 4/5 AEs | ||
| Hickerson et al., 2019 | N/S | 19.4 m | Statistically significant difference in 24-m DFS (p = 0.02, HR = 0.26) | Safe, no grade 4/5 AEs | ||
| Hale et al., 2018 | N/S | 18.8 m | Statistically significant difference in 24-m DFS in total (HR = 0.29) and HLA-A24+ pts (p = 0.02, HR = 0.08) | N/S | ||
| Tecemotide | Singer et al., 2020 * | 116 (62:54) | E 18 C 19 (90 mg/m2 and 600 mg/m2 q3w, respectively), and D 20 (100 mg/m2, 3qw) or vice-versa, x4 + cyclophosphamide (300 mg/m2) 3 days before vaccine + tecemotide (930 µg), x8 qw (VG)/ EC (90 mg/m2 and 600 mg/m2 q3w, respectively), and D (100 mg/m2, 3qw) or vice-versa, x4 (CG) SC 21 1 booster 2-3 weeks after last cycle |
29.5 w | No statistically significant differences in either RCB 22 or pCR 23 (data not disclosed) | No different AEs between CG and VC, except for injection site AEs |
| AS/OBI-821 | Huang et al., 2020 * | 45 (28:17) | cyclophosphamide (300 mg/m2) 3 days before vaccine at weeks 1, 5, 9, 13, 17, 25, 37 + AS/OBI-821 (30 µg/100 µg) at weeks 1, 2, 3, 5, 9, 13, 17, 25, 37 (VG)/ cyclophosphamide (300 mg/m2) 3 days before vaccine at weeks 1, 5, 9, 13, 17, 25, 37 + placebo at weeks 1, 2, 3, 5, 9, 13, 17, 25, 37 (CG) SC |
22.3 m | No statistically significant differences in PFS 24 | All injection-site and most non-injection site AEs of grade 1/2, 2 hypersensitivity and 1 fever cases in VG |
| PVX-410 |
Isakoff et al., 2022 | 19 (nr 25) | pembrolizumab 200 mg, q3w starting at 2nd vaccine dose+ PVX-410 (800 µg), x5 qw 2 boosters at w10 and 28 SC |
36.8 m | PFS = 2.3 m, OS 26 = 2.3 m; best overall response was SD 27 in 47% of pts, CBR 28 = 31.6%, no pts had CR 29 /PR 30 | Mostly grade 2 AEs, 2 grade 3 and 1 grade 4 AEs were attributable to pembrolizumab, no grade 5 AEs |
| Isakoff et al., 2020 | 22 (nr) | durvalumab 1500 mg, x2, with 4th and 6th vaccine doses + PVX-410 (800 µg), x6 q2w SC |
15.4 m | PVX-specific responses in 10/12 pts up to w 14 and persisted up to 6 m; 1/22 pt had local and 3/22 pts had metastatic recurrence, 2/22 pts died |
No DLT 31 s, mostly injection site AEs, 2 grade 3 diarrhea and hyponatremia, respectively, no grade 4/5 AEs | |
| H/K-HELP | Nishimura et al., 2011 | N/S | H/K-HELP x4 q2w SC |
N/S | Complete regression of resistant cervical node recurrence in TNBC pt | N/S |
| Ohtake et al., 2014 * | 1 | 71 d | ||||
| Personalized peptide vaccination (PPV) | Toh et al., 2012 | 8 (nr) | 1st cycle: PPV (3mg/each peptide), x6 qw; 2nd cycle: PPV (with re-selected peptides, 3 mg/each peptide), x6 q2w 3rd cycle: PPV (with re-selected peptides, 3 mg/each peptide), q4-8w continued until disease progression SC |
N/S | Total population: 2 pts had CR and 1 pt had PR; no significant difference between TNBC and other subtypes in clinical responses | No vaccine-related SAE 32 s |
| Takahashi et al., 2012 | 8 (nr) | N/S | 6/8 pts received ≥6 vaccine doses; 5/6 pts reached SD, 1/6 pt reached CR |
N/S | ||
| Toh et al., 2013 | 14 (nr) | 20.7 m | Median PFS and OS of TNBC were 8.3 m and 12 m, respectively | No vaccine-related SAEs | ||
| Takahashi et al., 2014 * | 18 (nr) | N/S | 1/18 pt had CR, 1/18 pt had PR; median PFS 7.5 m, median OS 11.1 m; no significant PFS and OS difference between PPV mono (16 pts)/combination chemotherapy (2 pts) (p = 0.467 and 0.347, respectively) | No vaccine-related SAEs | ||
| KRM-19 | Toh et al., 2020 * | 14 (nr) | KRM-19 (19 mg/mL, 1 mg of each peptide), x6 qw SC |
12 m | 6/14 pts had SD, 8/14 had PD 33; median PFS: 1.5 m in 14/14 pts, and 5.8 m in 10/14 pts completing vaccination series; median OS: 11.5 m in 14/14 pts, and 24.4 m in 10/14 pts completing vaccination | Most commonly injection site AEs (9 pts) and lymphocytopenia (4 pts), 5 pts with grade 3, 0 with grade 4, and 2 with grade 5 AEs |
| Toh et al., 2017 | 10 (nr) | N/S | 1/8 pt had PR, 4/8 pts had SD, 3/8 pts had PD; 12.5% ORR 34, 62.5% CBR | 10/10 pts had grade 1/2 injection site AEs, 5/10 pts had grade 2/3 liver function disorder, 3/10 pts had grade 2 bone marrow suppression, 1/10 pt had grade 2 nausea | ||
| Multipeptide active immunotherapy | Marquez-Manriquez et al., 2018 | 10 (nr) | oxaliplatin + doxorubicin (low-dose), x4 q2w + 22 peptides, x4 qw SC |
N/S | All pts entered remission according to CT 35, all pts had significant CD8 response against all peptides | Well-tolerated in all pts, minimal injection site AEs |
| Tumor lysate-pulsed DC 36 vaccine | Santisteban et al., 2021 * | 30 (nr) (17:13) | NAC (dd 37 EC x4 → D x4) + DCV 38, x5 q3w+ x1 the day after surgery + RT 39+ DCV, x4 q2m (VG)/NAC (ddEC x4 → D x4) (CG) ID |
8 y | TNBC pts: pCR 50% (VG) vs. 30.7% (CG); p = 0.255 | No difference in grade 3/4 NAC AEs between groups, no grade ≥ 3 vaccine-relate AEs |
| Elarre et al., 2016 | 30 (nr) | N/S | TNBC pts: pCR 67% (VG) vs. 17% (CG); increased TIL 40s observed in TNBC pts unlike other subtypes (p = 0.01) | N/S | ||
| Urrizola et al., 2020 | N/S | 7.52 y | Total pts (83): statistically significant pCR improvement (p = 0.03) TNBC pts: pCR 50.0% (VG) vs. 30.7% (CG) |
No difference in grade 3/4 NAC AEs between groups, no grade ≥ 3 vaccine-relate AEs | ||
| Antigen-loaded DC vaccine | O’Shaughnessy et al., 2020 | 10 (nr) | ddA 41 C + T 42 Cb 43 + DCV (x4 pre-surgery, x3 post-surgery) IT 44, SC |
N/S | 4/10 pts achieved pCR, 3/10 pts had local macroscopic residual disease, 3/10 pts had MRD 45 | N/S |
| Palucka et al., 2018 | 10 (nr) | 12 | All pts received 4 pre-surgery doses, 7/10 pts received all vaccine doses; 4/10 pts achieved pCR, 3/10 pts had local macroscopic residual disease, 3/10 pts had MRD | N/S | ||
| O’Shaughnessy et al., 2016 | 10 (nr) | N/S | All pts received 4 pre-surgery doses, 4/10 pts received all vaccine doses; 5/10 pts achieved pCR, 3/10 pts had local macroscopic residual disease, 2/10 pts had MRD | 9/10 pts had grade 1/2 injection site AEs | ||
| RO7198457 (iNEST) | Lopez et al., 2020 | 24 (nr) | atezolizumab (1200 mg) q3w+ RO7198457, x9 q1/2w for 12w (induction stage) and q24w (maintenance stage) | N/S | ORR = 4% in the TNBC cohort, and 8% in total pt population (108) | Majority of AEs of grade 1/2, no DLTs |
| p53MVA | Chung et al., 2019 * | 7 (nr) | p53MVA (5.6*108 pfu 46), x3 q3w + pembrolizumab (200 mg), x7 q3w IM 47 |
N/S | 1/7 pt failing all prior therapy lines had regression of cutaneous metastases (pCR), 5/7 pts were removed from the study due to PD at week 10, 1/7 pt had SD for 30 w | 1/11 pts grade 3 adrenal insufficiency, 2/11 pts LFT 48 rise, 1/11 pts grade 5 myocarditis (all mainly related to pembrolizumab) |
| Chung et al., 2018 | N/S | N/S | 1 pt had durable p53-specific CD8 responses along with pCR and SD for >6 m, 1 pt was on study for 35 w, 2 pts had rapidly PD | N/S | ||
| Yuan et al., 2017 * | 1 (case report) | 33 w | Sustained (6 m) and complete regression of cutaneous metastases after 9 w of treatment, minimal dermal relapse at week 33 | Grade 2 nausea, grade 1 vomiting, grade 1 skin rash (possibly related to pembrolizumab) | ||
| NANT cancer vaccine (NCV) | Nangia et al., 2019 | 9 (nr) | Low-dose metronomic chemoradiation + N-803 +PD-L1 49 inhibitor + haNK cells 50 + NCV (3w cycle) N/S route of administration |
N/S | DCR 51 = 78% (7/9 pts with CR + PR + SD); ORR = 56% (5/9 pts with PR + CR); CR in 2 pts (22%) | 4/9 pts had 8 grade ≥3 AEs (of which 2 pts had haNK-associated SAEs) |
| Nangia et al., 2019 | 8 (nr) | N/S | 1/8 pt had CR, 2/8 pts had PR | all pts had at least 1 grade ≥3 AEs, 2/8 pts had grade ≥ 3 haNK-associated AEs | ||
| Carlson et al., 2018 | 3 (nr) | N/S | 2/3 pts had PR | 4 hematologic DLT’s were observed and managed with dose reduction of cisplatin | ||
| Elenagen | Ponomarenko et al., 2020 * | 1 (case report) | Elenagen (1 mg), x5 qw, then q3w until disease progression ± CM 52 F 53 (C 600 mg/m2, M 40 mg/m2, F 600 mg/m2), days 1st and 8th q2w IM |
N/S | PFS = 19 w, 33% partial tumor regression | Grade ½ nausea, grade 2/3 leukopenia and neutropenia |
| Ponomarenko et al., 2017 * | 4 (nr) | N/S | In monotherapy: 2/4 pts had PD; 2/4 pts had SD for 8 & 32 w; in Elenagen + CMF: prolongation of SD in pts with PD (for 24 w) or those with SD (24 w) | Safe with no DLTs/SAEs, only grade 1 injection site AEs, nausea, fatigue, fever |
1 VG: vaccine group; 2 CG: control group; 3 m: month; 4 w: week; 5 d: day; 6 ID: intradermal; 7 y: year; 8 DFS: disease-free survival; 9 HR: hazard ratio; 10 AE: adverse event; 11 N/S: not specified; 12 pt: patient; 13 RR: recurrence risk; 14 LD: loading dose; 15 MD: maintenance dose; 16 IHC: immunohistochemistry; 17 NAC: neoadjuvant chemotherapy; 18 E: epirubicin; 19 C: cyclophosphamide; 20 D: docetaxel; 21 SC: subcutaneous; 22 RCB: residual cancer burden; 23 pCR: pathological complete response; 24 PFS: progression-free survival; 25 nr: non-randomized; 26 OS: overall survival; 27 SD: stable disease; 28 CBR: clinical benefit rate; 29 CR: complete response; 30 PR: partial response; 31 DLT: dose-limiting toxicity; 32 SAE: severe adverse event; 33 PD: progressive disease; 34 ORR: objective response rate; 35 CT: computed tomography; 36 DC: dendritic cell; 37 dd: dose-dense; 38 DCV: dendritic cell vaccination; 39 RT: radiotherapy; 40 TIL: tumor infiltrating lymphocyte; 41 A: doxorubicin; 42 T: paclitaxel; 43 Cb: carboplatin; 44 IT: intratumoral; 45 MRD: microscopic residual disease; 46 pfu: plaque-forming units; 47 IM: intramuscular; 48 LFT: liver function test; 49 PD-L1: programmed death-ligand 1; 50 ha-NK cells: high-affinity natural killer cells; 51 DCR: disease control rate; 52 M: methotrexate; 53 F: fluorouracil.