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. 2017 Sep 4;28(12):2950–2961. doi: 10.1093/annonc/mdx503

Table 1.

Selected completed trials assessing vaccine-based immunotherapeutic approaches in PDAC

Identification Trial and strategy Mechanism of action Study design Results
Lepisto et al. [19] Phase 1/2 study of mucin-1 loaded dendritic cells in adjuvant setting Activation of T cells against Mucin-1 expressing PDAC cells 1 × 106 Dendritic cells loaded with mucin-1 peptide were administered in the adjuvant setting at week 1, week 3, week 6 and 6 months to 12 months Well tolerated with no toxicity. N=4 of 12 patients had 4-year disease-free survival
Bernhardt et al. [21] Phase 1/2 study of telomerase as a cancer vaccine in combination with GM-CSF in advanced stage PDAC patients Induction of T-cell clones reactive to telomerase

  • Arm A: low-dose telomerase.

  • Arm B: intermediate dose telomerase.

  • Arm C: high-dose telomerase

 Well tolerated. Median OS 8.6 months in intermediate group and was significantly better compared with low- and high-dose groups (P=0.006 and P=0.05, respectively)
Middleton et al. [22] Phase III study of telomerase as a cancer vaccine in combination with gemcitabine and capecitabine in advanced stage PDAC patients Induction of T-cell clones reactive to telomerase and enhancement of clinical response to chemotherapy

  • Arm A: chemotherapy alone.

  • Arm B: chemotherapy with sequential telomerase peptide

  • Arm C: chemotherapy with concurrent telomerase peptide

 Neither concurrent or sequential telomerase vaccine therapy improved the clinical outcomes (P=0.6)
Jaffee et al. [28] Phase I study of GVAX alone in stage 1, 2, and 3 PDAC patients Activation of CTLs with GM-CSF secreting PDAC cells

  • Arm A: patients received 1 x 107 vaccine cells

  • Arm B: patients received 5 x 107 vaccine cells

  • Arm C: patients received 10 x 107 vaccine cells

  • Arm D: patients received 50 x 107 vaccine cells

  • Well tolerated.

  • GVAX with a dose of ≥ 10 x 107 vaccine cells induced delayed hypersensitivity reaction and appears to correlate with disease-free survival
Laheru et al. [29] Phase I study of GVAX in combination with low-dose cyclophosphamide (Cy/GVAX) in advanced PDAC Activation of CTLs with GM-CSF secreting PDAC cells and inhibition of regulatory T cells Arm A: six doses of GVAX with 21-day intervals.Arm B: cyclophosphamide 1 day prior to GVAX initiation followed by 6 doses of GVAX Both approaches were well tolerated with minimal toxicity. GVAX in combination with cyclophosphamide demonstrated a tendency toward better clinical outcomes (4.3 versus 2.3 months)
Le et al. [30] Phase II trial of Cy/GVAX in combination with CRS-207, as compared with GVAX alone in advanced stage PDAC patients Activation of CTLs with GM-CSF secreting PDAC cells, mesothelin and inhibition of T regulatory cells

  • Arm A: two doses of Cy/GVAX with subsequent four doses of CRS-207.

  • Arm B: six doses of Cy/GVAX with 21-day intervals

 OS was 6.1 months versus 3.9 months in arm A and arm B, respectively (P=0.02). Enhanced mesothelin specific T-cell clones were associated with a better prognosis
ECLIPSE trial [31] Phase IIb trial of Cy/GVAX in combination with CRS-207 versus GVAX alone versus physician choice chemotherapy in advanced stage PDAC patients Activation of cytotoxic T cells with GM-CSF secreting PDAC cells and inhibition of T regulatory cells

  • Arm A: GVAX and CRS-207

  • Arm B: CSR-207 alone

  • Arm C: physician choice chemotherapy

 No evidence of benefit. OS was 3.8 months, 5.4 months and 4.6 months in GVAX and CRS-207, CSR-207 alone and chemotherapy alone, respectively
Hardacre et al. [33] Phase II trial of Algenpantucel-L in combination with chemotherapy in resectable PDAC Induction of cytotoxic T cells against PDAC cells with hyperacute rejection (hypothetical) Single arm: 100 million vaccine cells injected intradermally for up to 14 vaccinations over 8 months in combination with chemo in adjuvant setting A trend toward improved clinical outcomes. Twelve-month disease-free survival and 12-month overall survival were 62% and 86%, respectively
IMPRESS trial [34] Phase III trial of Algenpantucel-L in combination with chemotherapy versus chemotherapy alone in resected PDAC patients Induction of cytotoxic T cells against PDAC cells with hyperacute rejection (hypothetical)

  • Arm A: up to 18 immunizations of 300 million immunotherapy cells in combination with standard care in adjuvant settings.

  • Arm B: standard care

 No evidence for benefit. Three- and four-year survival were 41.4% versus 42.1% and 32.6% versus 32.7% for the control and study groups, respectively. The median OS was 30.4 and 27.3 months for the control and study group, respectively

PDAC, pancreatic adenocarcinoma; CTL, cytotoxic T cells; DCs, dendritic cells; OS, overall survival; DLT, dose-limiting toxicity.