Table 1.
Selected phase II and III vaccine trials in lung, RCC and melanoma
| Agent and trial | Phase | Design and description | n | Results and comments |
|---|---|---|---|---|
| MAGE-A3 vaccine with AS02 adjuvant37 | II | Randomized trial of vaccine or placebo post resection of stage IB and II MAGE-A3+ NSCLC | 182 | Gene expression profile revealed a 43% reduction of recurrence in vaccine treated group (HR 0.57, 95% CI 0.36–1.2, P = 0.99). Primary end point of disease-free interval was not significantly different between the two groups (HR 0.74, P = 0.107) |
| Liposomal MUC-1 peptide vaccine (L-BLP-25)64 | II | Randomized trial of L-BLP-25 vs BSC in patients with stage IIIB or IV NSCLC with stable or responsive disease post chemotherapy or chemoradiation | 171 | Primary end point of median OS 17.2 months L-BLP-25 vs 13 months BSC (P = 0.066); subgroup analysis: stage IIIB patients OS 30.6 months vs 13.3 months in BSC arm |
| Vacccinia/MUC-1 vaccine (TG4010)69 | II | Randomized trial of cisplatin and vinorlbine with TG4010 vs TG4010 as a single agent until disease progression followed by addition of vinorelbine and cisplatin in patients with MUC-1-positive advanced NSCLC | 65 | Primary end point of response was met only for the concurrent TG4010 and chemotherapy arm; response rate 29.5% |
| Vacccinia/MUC-1 vaccine (TG4010)70 | IIB | Randomized trial of gemcitabine and cisplatin vs the same combination with TG4010 in patients with stage 4 NSCLC | 108 | Patients with normal level of activated NK cells at baseline had an improvement in 6-month PFS and OS. Patients with high levels of active NK cells had increased toxic effects. Primary end point of 6-month PFS met only for the concurrent TG4010 arm (43%), but not significantly different from chemotherapy alone (35%) |
| Allogeneic whole cell NSCLC line vaccine with anti-sense TGF-β (Belagenpumatucel-L)49 | II | Randomized multi-dose trial in NSCLC with low volume stage II, IIIA, IIIB, IV disease | 75 | Response rate 15%; OS, 441 days in advanced-stage disease setting |
| MAGE-A3 NCT00480025 | III | Randomized phase III trial of patients with resected stage IB–IIIA MAGE-A3+ NSCLC post resection or adjuvant chemotherapy | 2,289 | Primary end point: DFS |
| L-BLP-25 NCT00409188 | III | Randomized trial comparing vaccine vs placebo in patients with unresectable stage III with stable or responding disease after chemoradiotherapy | 1,464 | Primary end point: OS not met |
| L-BLP-25 NCT01015443* | III | Randomized trial comparing vaccine vs placebo in patients with unresectable stage III with stable or responding disease after chemoradiotherapy | 420 | Primary end point: OS |
| L-BLP-25 NCT00828009‡ | II | BLP25 vaccine and bevacizumab after chemoradiotherapy for patients with unresectable stage IIIA/B NSCLC | 55 | Primary end point: safety |
| TG4010 NCT01383148 | IIB/III | Randomized trial comparing platinum combination chemotherapy with or without vaccine in patients with stage IV NSCLC | 1,000 | Primary end point: OS |
| Belagenpumatucel-L NCT00676507 | III | Randomized trial of vaccine or placebo in patients with stage IIIA, IIIB or IV NSCLC with stable or responding disease after initial chemotherapy | 506 | Primary endpoint: OS |
| Multipeptide vaccine with GM-CSF adjuvant (IMA901)38 | I | Phase I study of multi-peptide vaccine in advanced RCC, patients must be HLA-A*02+ | 28 | Well tolerated, one partial response |
| Multipeptide vaccine with GM-CSF adjuvant (IMA901)38 | II | Randomized phase II study, patients received vaccine ± immunomodulatory cyclophosphamide. HLA-A*02+ patients | 68 | TREG depletion noted in cyclophosphamide arm. Well tolerated, one PR. Trend toward improved OS in vaccine + low-dose cyclophosphamide arm (HR = 0.57, P = 0.090) |
| Tumour RNA pulsed autologous DCs (AGS-003)55 | II | Single arm phase II study in patients with newly diagnosed clear cell RCC undergoing resection. Vaccine administered + sunitinib | 25 | Well-tolerated. Median PFS from registration for patients receiving at least one dose of AGS-003 was 11.9 months. Median OS from registration not yet reached |
| IMA901 with GM-CSF adjuvant NCT01265901‡ | III | Randomized, controlled study in the first-line setting in combination with sunitinib. Vaccine administered and low-dose cyclophosphamide. Patients must be HLA-A*02+ | 330 | Primary end point: OS secondary end point: OS in patients with favourable gene signature. Enrolment completed |
| RNA-loaded autologous DC vaccine (AGS-003) NCT01582672 | III | Randomized phase III trial of standard of care sunitinib ± vaccine in advanced RCC | 450 | Primary end point: OS |
| Melanoma | ||||
| gp100111 | III | gp100 peptide in montanide + high-dose IL-2 vs IL-2 alone | 185 | Clinical response rate and PFS significantly higher in combination group |
| Allovectin-7 NCT00395070§ | III | Allovectin 7 vs DTIC or temozolomide in unresectable stage III/IV melanoma | ~375 | Primary outcome measures: ORR at ≥24 weeks; secondary outcome measures: safety/tolerability of Allovectin-7; OS |
| MAGE-A3 NCT00796445§ | III | MAGE-A3 vaccine vs placebo in patients with surgically resected stage IIIB/C cutaneous melanoma with macroscopic lymph-node involvement | 1,349 | Secondary outcome measures include Anti-MAGE-A3 and anti-protein D seropositivity status. Primary outcome measure: DFS |
| GVAX melanoma NCT01435499‡ | I | Allogeneic, GM-CSF secreting, whole melanoma cell vaccine administered with or without low-dose cyclophosphamide to patients with resected stage IIB–IV melanoma | 19 | Secondary outcome measures include in vitro correlates of anti-melanoma immunization (serological and cellular immune responses). Primary outcome measures: safety, tolerability; secondary outcome measures: in vitro correlates of anti-melanoma immunization |
| T-Vec74§ | III | T-Vec (attenuated herpes simplex virus) vs GM-CSF | 436 | Durable response rate 16.3% (T-Vec) vs 2.1% (GM-CSF) |
*
Trial status ongoing in Asia.
‡
Trial status ongoing.
§
Completed enrolment.
Abbreviations: BSC, best supportive care; CD, dendritic cells; DFS, disease-free survival; DTIC, dacarbazine; GM-CFS, granulocyte-macrophage colony stimulating factor; HR, hazard ratio; NK, natural killer; NSCLC, non-small-cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; RCC, renal cell carcinoma; RR, relative risk; vs, versus.