Therapeutic vaccines may prove both effective and directed as cancer treatments
Therapeutic vaccines may prove both effective and directed as cancer treatments. One such product, being developed by Immatics Biotechnologies, is based on a selection of naturally presented tumour-associated peptides. Two versions are currently in the clinic – IMA901 for renal cell carcinoma, and IMA910 for colorectal cancer.
In a Phase II trial, 68 patients with clear cell renal cell carcinoma that was HLA-A*02+ and documented progression after first line therapy of either cytokine or a TKI-based therapy were given up to 17 intradermal vaccinations of IMA901 over nine months, along with 75g GM-CSF and/or a single 300mg/m2 infusion of low dose cyclophosphamide as an immunomodulator before the first vaccination.1 After six months, the overall disease control rate was 31% in the group pre-treated with cyclophosphamide, and 12% in the post-TKI group. The safety profile was good, with most adverse events being local injection site reactions.
Further positive Phase II results were seen with IMA910 in patients with HLA-A*02+ advanced colorectal cancer who had shown no progression after 12 weeks of first line oxaliplatin based chemotherapy.2
Ninety-two patients were given a single infusion of cyclophos-phamide prior to the first vaccination; this was given alongside GM-CSF, and either with or without the immunomodulator imiquimod. They were given up to 16 vaccinations over nine months. Most experienced an immune response stimulated by the vaccine, and those in whom both CD8+ and CD4+ responses were triggered did not reach the median survival after more than 28 months of follow-up, compared with 16 months in those who did not.
IMA901 is now undergoing a Phase III trial in renal cell carcinoma in combination with Pfizer’s sunitinib to see if the co-administration will improve survival rates further by sunitinib favourably altering immune regulation via a reduction of Treg and myeloid-derived suppressor cells.3
1. C. Reinhardt et al. J. Clin. Oncol. 2010, 28 (suppl.), Abst. 4529
2. F. Mayer et al. J. Clin. Oncol. 2012, 20 (suppl. 4), Abst. 555
3. B.I. Rini et al. J. Clin. Oncol. 2011, 29 (suppl.), Abst. TPS183