Table 1.
Select unsuccessful pivotal trials for therapeutic cancer vaccines
| Vaccine platform type | Autologous or allogeneic | Product/compound name | Antigen(s) | Antigen rankinga | Identifier (phase, name) | Patient population | Regimens | Findings | Possible reason(s) for lack of trial success | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| Viral vector | Allogeneic | PANVAC™-VF (falimarev) | MUC1, CEA | 2, 13 | NCT00088660 (phase 3) | Metastatic (stage IV) pancreatic cancer; already failed prior Gem | PANVAC™-VF + GM-CSF vs. BSC or palliative chemotherapy | Primary endpoint (OS) not met | Tumor burden (inappropriate population for vaccine monotherapy) | [15] |
| Viral vector | Allogeneic | PROSTVAC-V/F | PSA | 22 | NCT01322490 (phase 3, PROSPECT) | Asymptomatic/minimally symptomatic mCRPC | PROSTVAC ± GM-CSF vs. placebo |
Primary endpoint (OS): Placebo: 34.3 months PROSTVAC: 34.4 months (HR comparison with placebo: 1.01 [95% CI 0.84–1.20, p = 0.47]) PROSTVAC + GM-CSF: 33.2 months (HR comparison with placebo: 1.02 [95% CI 0.86–1.22, p = 0.59]) |
Insufficient immune response or negative regulatory influences in the TME Ineffective as monotherapy Phase 2 false positive (underpowered for OS comparison) Potential for prolonged OS in the control arm relative to expected due to increasing availability of multiple life-extending treatments since the study was designed |
[16] |
| Viral vector | Allogeneic | CMB305 | NY-ESO-1 | 10 | NCT02609984 (phase 2, IMDZ-C232) | NY-ESO-1 + soft tissue sarcoma | CMB305 + atezolizumab vs. atezolizumab |
Primary endpoints (OS, PFS), CMB305 + atezolizumab vs. atezolizumab: OS: 18.2 months vs. 18.0 months PFS: 2.8 months vs. 1.6 months |
Imbalances in patient/disease characteristics: combination arm had more advanced disease and more prior lines of chemotherapy | [17] |
| Cell-based (tumor cell) | Allogeneic | Belagenpumatucel-L (Lucanix™) | – | – | NCT00676507 (phase 3) | Stage III/IV NSCLC; stable disease following frontline, platinum-based chemotherapy | Belagenpumatucel-L vs. placebo | Primary endpoint (OS), belagenpumatucel-L vs. placebo: median 20.3 months vs. 17.8 months (HR 0.94; 95% CI 0.73–1.20; p = 0.59); at second interim analysis, study was terminated for futility |
Study design (late enrollment after induction therapy; single-agent therapy) Study did not require prior radiation within 6 months of randomization, which may have improved OS |
[18] |
| Cell-based (tumor cell) | Allogeneic | GVAX® | – | – | NCT00089856 (phase 3, VITAL-1) | Metastatic, hormone-refractory prostate cancer | GVAX® vs. docetaxel + prednisone |
Median survival (GVAX® vs. docetaxel + prednisone): 20.7 months vs. 21.7 months (p = 0.78) Study terminated based on futility analysis showing < 30% chance of meeting primary endpoint Terminated early from lack of therapeutic effect |
– | [11, 19] |
| Cell-based (tumor cell) | Allogeneic | GVAX® | – | – | NCT00133224 (phase 3; VITAL-2) | Taxane-naïve, metastatic, hormone-refractory prostate cancer patients with pain | GVAX® + docetaxel vs. docetaxel and prednisone |
OS (GVAX® + docetaxel vs. docetaxel and prednisone): 12.2 months vs. 14.1 months (p = 0.01) Accrual and treatment with GVAX® stopped because of IDMC recommendation Terminated early from lack of therapeutic effect |
– | [11, 19] |
| Cell-based (tumor cell) | Allogeneic | Canvaxin™ (CancerVax) | – | – | NCT00052130 (phase 3, MMAIT-III) | Completely resected stage III melanoma | Canvaxin™ + BCG vs. BCG | Based on DSMB recommendation, study was terminated (low probability demonstrating significant improvement in Canvaxin™-containing treatment arm) | Population heterogeneity (burden of disease, heterogeneity of disease, immunological response) | [20, 21] |
| Cell-based (tumor cell) | Allogeneic | Canvaxin™ (CancerVax) | – | – | NCT00052156 (phase 3, MMAIT-IV) | Completely resected stage IV melanoma | Canvaxin™ + BCG vs. BCG | Primary endpoint (OS), Canvaxin™ + BCG vs. BCG: median 38.6 months vs. 34.9 months (HR 1.04; 95% CI 0.80–1.35; p = 0.77) | High survival in both treatment arms may be a result of selection bias, beneficial effect of metastasectomy, and/or use of BCG in control treatment arm | [20, 22] |
| Cell-based (tumor lysate) | Allogeneic | Melacine (theraccine) | – | – |
– (phase 3) |
Resected, intermediate-thickness, node-negative melanoma | After surgery: Melacine + DETOX adjuvant therapy vs. no further treatment |
Primary endpoint (DFS, OS), vaccine vs. no treatment DFS: 107/300 events (tumor recurrences or deaths) vs. 114/300 (HR 0.92; Cox-adjusted P2 = 0.51) OS: Not mature at time of publication |
Study design (inadequately powered to detect small, clinically meaningful differences; methodology for staging regional nodes) Population heterogeneity |
[23] |
| Cell-based (tumor lysate) | Allogeneic | Melacine (theraccine) | – | – |
– (phase 3) |
Stage IV melanoma with ≥ 1 measurable lesion(s), ECOG PS 0–1 | Melacine vs. DTIC, cisplatin, BCNU, and tamoxifen | Median survival (melacine vs. chemotherapy): 9.4 months vs. 12.3 months (p = 0.16) | – | [24] |
| Cell-based (tumor cell) | Allogeneic | Algenpantucel-L (HyperAcute® platform) | – | – | NCT01072981 (phase 3, IMPRESS) | Surgically resected pancreatic cancer, stage I or II (per AJCC) | Algenpantucel-L + SOC (Gem ± 5FU chemoradiation) vs. SOC alone | Primary endpoint (OS), algenpantucel-L + SOC vs. SOC: 30.4 months vs. 27.3 months; primary endpoint was not achieved | – | [25] |
| Cell-based (virus-augmented tumor cell) | Allogeneic | VMCL | – | – | – | Cutaneous melanoma; stage IIB or stage III (per AJCC); regional nodal involvement without evidence of systemic metastatic disease | VMCL vs. observation |
Median RFS: In eligible patients: 6.9 vs. 3.6 years (HR 0.86; 95% CI 0.70–1.07; p = 0.17) In ITT patients: 6.98 vs. 4.37 years (HR 0.89; 95% CI 0.72–1.09; p = 0.27) Median OS: In eligible patients: 12.6 vs. 7.3 years (HR 0.81; 95% CI 0.64–1.02; p = 0.07) In ITT patients: >8.45 vs. 7.34 years (HR 0.83; 95% CI 0.67–1.04; p = 0.11) |
Better survival of control treatment arm in phase 3 study compared with phase 2 study | [26] |
| Cell-based (virus-augmented tumor cell) | Allogeneic | VMO | – | – |
– (phase 3) |
Stage II melanoma (per IUAC) with positive lymph nodes | VMO vs. control (vaccinia virus alone) | Median disease-free interval, VMO vs. control: 38.0 months vs. 37.0 months (p = 0.99) | Population heterogeneity (potential differences for male vs. female patients) | [27] |
| Cell-based (virus-augmented tumor cell) | Allogeneic | VMO | – | – |
– (phase 3) |
Stage III melanoma (per AJCC) | VMO vs. control (vaccinia virus alone) |
Median disease-free interval, VMO vs. control: 20.7 months vs. 26.9 months (p = 0.61) Median OS, VMO vs. control: 50.2 months vs. 41.3 months (p = 0.79) Median OS, 10-year follow-up, VMO vs. control: 7.71 years vs. 7.95 years (p = 0.70) |
Population heterogeneity (retrospective subset analysis showed that a subgroup of men may have a survival advantage with VMO) | [28, 29] |
| Cell-based (RNA electroporated DC) | Autologous | Rocapuldencel-T (AGS-003) | – | – |
(phase 3, ADAPT) |
Newly diagnosed metastatic RCC | Rocapuldencel-T + standard therapy vs. standard therapy alone | Primary endpoint (OS), rocapuldencel-T + standard therapy vs. standard therapy alone: median 27.7 months vs. 32.4 months (unadjusted HR 1.10; 95% CI 0.83–1.46; adjusted HR 1.06; 95% CI 0.79–1.40) | Insufficient long-term follow-up/potential delayed treatment effect | [30] |
| Cell-based (DC) | Autologous | Peptide-loaded DC vaccine | Several MHC class I- and class II-restricted peptides (9 or 10 mer)b | Includes 44, 8, 20, 16, 14 |
– (phase 3) |
Metastatic (stage IV) melanoma | DC vaccine vs. DTIC |
Primary endpoint (OR): < 6% in both treatment arms Following first interim analysis, study was prematurely closed (recommendation of external Data Monitoring and Safety Board because of extremely low probability of reaching study goals |
Population heterogeneity (significant differences in subgroups defined by performance status and HLA haplotype) | [31] |
| DNA vaccine | Allogeneic | Allovectin-7® (velimogene aliplasmid) | HLA-B7 and β2 microglobulin | – |
(phase 3) |
Recurrent stage III or stage IV melanoma | Allovectin-7® vs. chemotherapy alone (DTIC or TMZ) | No significant improvement in objective response rate at ≥ 24 weeks (primary endpoint) or OS (secondary endpoint); based on this outcome, Allovectin program has been terminated | – | [32–34] |
| Ganglioside | Allogeneic |
GM2-KLH (GMK) |
GM2 | – | EORTC 18961 (phase 3) | Stage II melanoma | GM2-KLH/QS-21 vs. observation after resection of primary tumor >1.5 mm |
Primary endpoint (RFS), GM2-KLH/QS-21 (n = 627) vs. observation (n = 627): Second interim analysis: 135 events vs. 132 events (HR 1.00; 98% CI 0.75–1.34; p = 0.99); trial was stopped for futility Final analysis: 205 vs. 204 events (HR 1.03; 98% CI 0.84–1.25; p = 0.81) |
Vaccination schedule (i.e., impact of multiple vaccinations may be deleterious) | [35] |
| Ganglioside | Allogeneic | GM2-KLH (GMK) | GM2 | – | Intergroup trial E1694/S9512/C509801 (phase 3) | Resected stage IIb/III melanoma (per AJCC) | GM2-KLH/QS-21 vs. HDI therapy |
Primary endpoint (RFS), GM2-KLH/QS-21 vs. HDI therapy: In eligible patients: 151/389 (39%) events vs. 98/385 (25%) events (HR 1.47; 95% CI 1.14–1.90; log-rank one-sided p < 0.05 in favor of HDI [p = 0.0015]) In ITT population: HR 1.49 (p < 0.05 in favor of HDI [p = 0.00045]) P values for RFS crossed protocol-specified lower boundary, resulting in study termination Primary endpoint (OS), GM2-KLH/QS-21 vs. HDI therapy: In eligible patients: (HR 1.52; 95% CI 1.07–2.15; log-rank one-sided p = 0.01 in factor of HDI) In ITT population: HR 1.38 (p = 0.02) |
– | [36] |
| Protein (anti-idiotypic antibody) | Allogeneic | Abagovomab | CA-125 (cleaved and released domain of MUC16) | – | NCT00418574 (phase 3, MIMOSA) | Stage III–IV epithelial ovarian, primary peritoneal, or fallopian tube cancer in first complete clinical remission | Abagovomab vs. placebo | Primary endpoint (RFS), abagovomab (n = 593) vs. placebo (n = 295): 374 recurrence events vs. 180 recurrence events (HR 1.10; 95% CI 0.92–1.32; p = 0.30) | Study design (combination therapies and multi-antigen approaches remain reasonable approaches to study) | [37] |
| Protein (anti-idiotypic antibody) | Allogeneic | BEC2 | GD3 | 40 | NCT00037713 (phase 3, SILVA) | Limited-disease SCLC | BEC2/BCG vs. observation | Primary endpoint (OS), BEC2/BCG vs. observation: median 14.3 vs. 16.4 months (HR 1.12; 95% CI 0.91–1.37; p = 0.28) |
Study design (imbalance in patient characteristics; choice of adjuvant or anti-idiotypic approach; single-antigen approach) Population heterogeneity and study design (GD3 is present in only ~ 60% of SCLC tissues and patients were not stratified by GD3 expression) Insufficient immune response (1/3 of patients developed humoral response) |
[38] |
| Protein (idiotype) | Autologous | MyVax (GTOP-99) | Patient-specific idiotype conjugated to KLH (recombinant DNA technique) | 7 | NCT00017290 (phase 3) | Previously untreated, advanced-stage (Ann Arbor stage III or IV) FL | MyVax + GM-CSF vs. control (KLH + GM-CSF) | Primary endpoint (PFS), MyVax vs. control: HR 0.98, 95% CI 0.72–1.33; p = 0.89 |
Insufficient humoral immune response (immune response observed in 41% of patients) Population heterogeneity (patients with better immune response had better PFS) Study design (choice of adjuvant) |
[39] |
| Protein (idiotype) | Autologous | Mitumprotimut-T (Specifid) | Patient-specific idiotype conjugated to KLH (recombinant DNA technique) | 7 |
– (phase 3) |
Treatment-naïve or relapsed/refractory CD20+ FL, WHO grade 1–3; candidate for rituximab | Mitumprotimut-T + GM-CSF vs. placebo (GM-CSF) | Primary endpoint (TTP), mitumprotimut-T vs. placebo: 9.0 months vs. 12.6 months (HR 1.38; 95% CI 1.05–1.82; p = 0.02) |
Imbalance in FLIPI risk groups Product (antigen and/or adjuvant selection) Insufficient immune response/inhibitory immune microenvironment |
[40] |
| Protein (idiotype) | Autologous | BiovaxID® | Patient-specific idiotype conjugated to KLH (hybridoma technique) | 7 | NCT00091676 (phase 3) | Advanced stage FL in first remission (CR or CR unconfirmed) after chemotherapy | BiovaxID® + GM-CSF vs. control (KLH + GM-CSF) |
Primary endpoint (DFS), BiovaxID® + GM-CSF vs. control: For all 177 randomly assigned patients (includes 60 patients who did not receive vaccination): 23.0 months vs. 20.6 months (HR 0.81; 95% CI 0.56–1.16; p = 0.26) For the 117 patients who received vaccination: 44.2 months vs. 30.6 months (HR 0.62, 95% CI 0.39-0.99; p < 0.05 [p = 0.047]) |
Study design (control treatment arm [KLH + GM-CSF vs. placebo]) Product (tumor Ig isotype may influence immunogenicity of vaccine) |
[41] |
| Protein | Allogeneic | THERATOPE® | STn | 56 | NCT00003638 (phase 3) | MBC; previously received chemotherapy and had CR, PR, or no disease progression | STn-KLH vs. KLH |
Primary endpoints (TTP and OS), STn-KLH vs. KLH: TTP: 3.4 months vs. 3.0 months (Cox p = 0.35) OS: 23.1 months vs. 22.3 months (Cox p = 0.92) |
Study design (KLH as control arm rather than no treatment) Tumor burden (advanced metastatic disease) Treatment duration (continued vaccination beyond primary progression may have been advantageous) |
[42] |
| Protein | Allogeneic | GSK2132231A | Recombinant MAGE-A3 | 8 | NCT00796445 (phase 3, DERMA) | Resected, MAGE-A3-positive, stage III melanoma | GSK2132231A + AS15 vs. placebo |
Primary endpoint (DFS), GSK2132231A + AS15 vs. placebo: In overall population: median 11.0 months vs. 11.2 months (HR 1.01; 95% CI 0.88–1.17; p = 0.86) In patients with potentially predictive gene signature: median 9.9 months vs. 11.6 months (HR 1.11; 95% CI 0.83–1.49; p = 0.48) |
Product (choice of antigen, immunostimulant) Insufficient/absent immune response Target population (too advanced for antigen-specific immunotherapeutic alone) |
[43] |
| Protein | Allogeneic | GSK1572932A | Recombinant MAGE-A3 | 8 | NCT00480025 (phase 3, MAGRIT) | Resected, MAGE-A3-positive, NSCLC | GSK1572932A + AS15 vs. placebo |
Primary endpoint (DFS), GSK1572932A + AS15 vs. placebo: In overall population: median 60.5 months vs. 57.9 months (HR 1.02; 95% CI 0.89–1.18; p = 0.74) In patients who did not receive chemotherapy: median 58.0 months vs. 56.9 months (HR 0.97; 95% CI 0.80–1.18; p = 0.76) In patients with potentially predictive gene signature: not evaluated, as predictive gene signature could not be identified |
Initial positive treatment effect in phase 2 trial may be a result of limited sample size and/or unnoticed imbalances across treatment groups | [44] |
| Protein | Allogeneic | G17DT (Insegia) | Gastrin-17 | – | NCT00044031 (phase 3) | Untreated with locally advanced, recurrent, or metastatic pancreatic cancer | G17DT + Gem vs. placebo + Gem | Primary endpoint (OS), G17DT + Gem vs. placebo + Gem: 178 days vs. 201 days (HR 1.10; p = 0.10) | Population heterogeneity (anti-G17 antibody levels correlated with OS) | [21] |
| Synthetic peptide (length: 25 mer) | Allogeneic | Tecemotide (L-BLP25, StimuVax) | MUC1 | 2 | NCT00409188 (phase 3, STARTc) | Unresectable stage III NSCLC | Tecemotide vs. placebo |
Primary endpoint (OS), tecemotide vs. placebo: 25.8 months vs. 22.4 months (adjusted HR 0.89; 95% CI 0.77–1.03; p = 0.11) |
Population heterogeneity (possibly more favorable effect in patients receiving concurrent as opposed to sequential chemoradiotherapy) Clinical hold potentially resulted in underestimated treatment effect |
[45, 46] |
| Synthetic peptide (length: 25 mer) | Allogeneic | Tecemotide (StimuVax; L-BLP25) | MUC1 | 2 | NCT00925548 (phase 3, STRIDE) | ER-positive and/or PgR-positive, inoperable, locally advanced, recurrent, or metastatic BC in post-menopausal women | Tecemotide + hormonal therapy vs. hormonal therapy | Sponsor permanently terminated trial following clinical hold | Safety concerns | |
| Synthetic peptide (16 mer) | Allogeneic | GV1001 | hTERT | 23 | ISRCTN4382138 (phase 3, TeloVac) | Locally advanced or metastatic pancreatic cancer; ECOG PS 0–2 | Chemotherapy alone (Gem and capecitabine); chemotherapy with sequential GV1001 + GM-CSF; chemotherapy with concurrent GV1001 + GM-CSF |
Primary endpoint (OS): Chemotherapy alone vs. sequential GV1001 + GM-CSF: median 7.9 months vs. 6.9 months (HR 1.19, 98.25% CI 0.97–1.48; p = 0.05) Concurrent GV1001 + GM-CSF: median 8.4 months (HR 1.05; 98.25% CI 0.85–1.29; p = 0.64; overall log-rank of χ22df = 4.3; p = 0.11) |
Nature of disease (early metastasizing, rapidly progressive may limit time to develop immune response; dense stromal reaction may impede/restrict synergistic potential of chemotherapy and GV1001) | [21, 47–49] |
| Synthetic peptide (16 mer) | Allogeneic | GV1001 | hTERT | 23 | NCT00358566 (phase 3, Primovax) | Advanced, unresectable pancreatic cancer; ECOG PS 0–1 | Gem alone vs. Gem with sequential GV1001 + GM-CSF | Preliminary data showed no survival benefit in GV1001 group vs. chemotherapy alone | – | [47, 49] |
| Synthetic peptide (14 mer) | Allogeneic | Rindopepimut (CDX-110) | EGFRvIII | 5 | NCT01480479 (phase 3, ACT IV) | Newly diagnosed, EGFRvIII-expressing glioblastoma | TMZ + rindopepimut + GM-CSF vs. control (TMZ alone) |
Primary endpoint (OS), TMZ + rindopepimut + GM-CSF vs. control: Study was terminated at the second interim analysis for futility In the ITT population: median 17.4 months vs. 17.4 months (HR 0.89, 95% CI 0.75–1.07; p = 0.22) In the MRD population: median 20.1 months vs. 20.0 months (HR 1.01; 95% CI 0.79–1.30; p = 0.93) |
Patients in control treatment arm fared better in this study than matched control datasets Study design (control arm [KLH vs. inactive placebo]; TMZ use [treatment-induced lymphopenia may reduce immunotherapy efficacy]; vaccine started after radiotherapy vs. as early as possible) Product (single antigen rather than multi-peptide vaccine or other combination approaches) |
[50, 51] |
| Synthetic peptide | Allogeneic | Elpamotide | VEGFR2 | 70 | UMIN000002500 (phase 2/3, PEGASUS-PC) | Locally advanced or metastatic pancreatic cancer | Elpamotide + Montanide™ ISA 51 VG vs. placebo (saline + Montanide™ ISA 51 VG) | Primary endpoint (OS), elpamotide + Montanide™ ISA 51 VG vs. placebo: median 8.36 months vs. 8.54 months (HR 0.87; 95% CI 0.49–1.56; H-F p = 0.92) |
Population heterogeneity (subgroup analyses suggested that patients with strong injection site reactions may benefit from the vaccine, but these patients were limited in number) Study design (use of Montanide™ ISA 51 VG in control arm; single vs. multiple tumor targets) |
[52] |
| Synthetic peptides (lengths: 9 mer; 9 mer; 9 mer) | Allogeneic | Peptide vaccine | Tyrosinase, gp100, MART-1/melan-A | 20, 16, 14 | ECOG E4697 study | Locally advanced (stage III) and/or stage IV melanoma with no evidence of disease after complete surgical resection | Peptide vaccine + Montanide™ ISA 51 ± GM-CSF vs. placebo ± GM-CSF | Secondary objective (RFS), peptide vaccine vs. placebo in HLA-A2+ patients: median 11.5 months vs. 9.8 months (HR 0.96; 95% repeated CI 0.74–1.23; p = 0.71) |
Population heterogeneity (sites of metastases, baseline immune status) Insufficient immune response or lack of relevance of immune response Product (adjuvant selection, administration) |
[53] |
| Synthetic peptide (length: 9 mer) | Allogeneic | Nelipepimut-S (E75; NeuVax™) | HER2 | 6 | NCT01479244 (phase 3, PRESENT) | T1–T3, node-positive BC with low to intermediate HER2 expression | Nelipepimut-S + GM-CSF vs. GM-CSF | Primary endpoint (DFS), nelipepimut-S (n = 376) vs. placebo (n = 382): 37 recurrence events vs. 24 recurrence events; no significant difference in DFS events (HR 1.564; 95% CI 0.96–2.55; p = 0.07) | Study design (protocol-specified annual imaging instead of clinical assessment per ASCO guidelines hastened interim analysis [clinical significance of image-only recurrence events unclear]) | [54, 55] |
| Protein-peptide complex | Autologous | Vitespen (HSPPC-96, Oncophage) | gp96-peptide complex | – | NCT00033904 (phase 3) | RCC at high risk of recurrence after nephrectomy | Vitespen vs. observation | Primary endpoint (RFS), vaccine vs. observation: 37.7% (136/361) vs. 39.8% (146/367) (HR 0.92; 95% CI 0.73–1.17; p = 0.51) |
Study design (higher than expected number of patients with metastatic disease) Population heterogeneity (more targeted recruitment may have allowed enrollment of patients with earlier stage disease and better prognosis) |
[56] |
| Protein-peptide complex | Autologous | Vitespen (HSPPC-96, Oncophage) | gp96-peptide complex | – |
(phase 3) |
Stage IV melanoma, with expected resectability of some/all lesions to obtain ≥ 7 g of cancer | Vitespen vs. physician’s choice (DTIC/TMZ and/or IL-2 and surgery) | Primary endpoint (OS), vaccine vs. physician’s choice: HR 1.16; 95% CI 0.69–1.71; p = 0.32 |
Study execution (49% success rate for vaccine production based on suggested minimum threshold of four administrations in animal models) Population heterogeneity (exploratory analyses showed that patients with earlier stages of disease may have benefited from the vaccine) |
[57] |
| Protein-peptide complex | Autologous | Vitespen (HSPPC-96, Oncophage) | gp96-peptide complex | – | NCT01814813 (phase 2) | Surgically resectable, recurrent glioblastoma | Vitespen + bevacizumab vs. bevacizumab alone | Primary endpoint (OS), vaccine + bevacizumab vs. bevacizumab alone at interim analysis: 7.5 months vs. 10.7 months (HR 2.06; 95% CI 1.18–3.60; p = 0.008); study terminated for futility | – | [58] |
| Oncolytic virus | Allogeneic | pexastimogene devacirepvec (Pexa-Vec) | – | – | NCT02562755 (phase 3) | Advanced HCC without prior systemic therapy | Pexa-Vec vs. sorafenib | Interim futility analysis determined that the primary objective (OS) was not likely to be met |
Difficult-to-treat population Immunosuppressive environment (liver) Imbalance between arms in salvage therapies received |
[59] |
AJCC American Joint Committee on Cancer, ASCO American Society of Clinical Oncology, BC breast cancer, BCG bacillus Calmette–Guérin, BCNU carmustine, BSC best supportive care, CEA carcinoembryonic antigen, CI confidence interval, CR complete response, DC dendritic cell, DETOX detoxified Freund’s adjuvant, DFS disease-free survival, DSMB Data and Safety Monitoring Board, DTIC dacarbazine, ECOG PS Eastern Cooperative Oncology Group performance status, EGFRvIII epidermal growth factor receptor variant III, EORTC European Organisation for Research and Treatment of Cancer, ER estrogen receptor, FL follicular lymphoma, FLIPI Follicular Lymphoma International Prognostic Index, Gem gemcitabine, GM-CSF granulocyte-macrophage colony-stimulating factor, HCC hepatocellular carcinoma, HDI high-dose interferon-α-2b, HER2 human epidermal growth factor receptor 2, H-F Harrington-Fleming test, HLA human leukocyte antigen, HR hazard ratio, HSPPC-96 heat shock protein peptide complex-96, hTERT human telomerase reverse transcriptase, IDMC independent data monitoring committee, Ig immunoglobulin, IL-2 interleukin-2, ITT intent-to-treat, IUAC International Union Against Cancer, KLH keyhole limpet hemocyanin, MAGE melanoma-associated antigen, MBC metastatic breast cancer, mCRPC metastatic castration-resistant prostate cancer, MHC major histocompatibility complex, MRD minimal residual disease, MUC1 mucin 1, NSCLC non-small-cell lung cancer, NY-ESO-1 New York esophageal squamous cell carcinoma 1, OR objective response, OS overall survival, PFS progression-free survival, PgR progesterone receptor, PR partial response, PSA prostate-specific antigen, RCC renal cell carcinoma, RFS recurrence-free survival, SCLC small-cell lung cancer, SOC standard of care, STn sialyl-Tn, TME tumor microenvironment, TMZ temozolomide, TTP time to progression, VEGFR2 vascular endothelial growth factor receptor 2, VMCL vaccinia melanoma cell lysate, VMO vaccinia melanoma oncolysate, WHO World Health Organization
aAntigen ranking based on Table 3 of Cheever, et al. Clin Cancer Res. 2009;15(17):5327–37[14]
bMHC class I- and II-restricted peptides included MAGE-1, MAGE-3, tyrosinase, gp100 analog, and MART-1/melan-A analog
cDiscontinuation of clinical development program for tecemotide monotherapy in stage III NSCLC also included phase 3 START2 (NCT02049151) and INSPIRE (NCT01015443) trials.