IMA901 Vaccine Offers No Additional Benefit To Sunitinib For Advanced RCC

Overall survival results do not support use of a multipeptide vaccine alongside sunitinib for treatment of advanced and metastatic renal cell carcinoma

medwireNews: The IMPRINT trial has failed to show an overall survival (OS) benefit for the addition of the multipeptide cancer vaccine IMA901 to sunitinib in HLA-A*02-positive patients with advanced or metastatic renal cell carcinoma (RCC).

“Sunitinib monotherapy remains the standard of care in patients with metastatic renal cell carcinoma”, Brian Rini, from Cleveland Clinic Taussig Cancer Institute in Ohio, USA, and co-investigators therefore conclude.

“Additional immune manipulations to substantially improve the magnitude and polarisation of immune responses (eg, in combination with checkpoint inhibition) are needed for IMA901 to have a meaningful clinical effect in this disease”, they write in The Lancet Oncology.

After a median of 33.27 months, OS was a median of 33.17 months for the 204 patients who were randomly assigned to receive sunitinib 50 mg/day with up to 10 intradermal doses of IMA901 4.13 mg plus granulocyte macrophage colony-stimulating factor 75 μg, as well as a single dose of cyclophosphamide 300 mg/m2 3 days before the first vaccination.

But median OS was not reached among the 135 patients who were given only the vascular endothelial growth factor–tyrosine kinase inhibitor (VEGF–TKI), giving a nonsignificant hazard ratio of 1.34.

For patients with a favourable International Metastatic Database Consortium risk, median OS was comparable between the sunitinib plus IMA901 and sunitinib alone treatment groups (not reached vs 33.73 months), while among those with an intermediate risk, median OS was significantly shorter with sunitinib plus IMA901 (27.85 months vs not reached).

“The numerically shorter overall survival in the sunitinib plus IMA901 group than in the sunitinib group might indicate a potentially harmful effect of vaccination”, the researchers comment.

“[H]owever, the more likely explanation is the exceptionally good outcome in the sunitinib monotherapy group, especially in intermediate-risk patients, compared with historical controls.”

Median progression-free survival was a comparable 15.22 months for patients given sunitinib plus IMA901 and 15.12 months for those given sunitinib alone.

Grade 3 or more severe adverse events occurred in 57% of patients given sunitinib plus IMA901 and 47% of those given sunitinib monotherapy, with hypertension, neutropenia and anaemia the most common side effects in both groups. The most common adverse event associated with IMA901 was a mild-to-moderate transient injection site reaction.

Serious adverse events leading to death occurred in 2% of patients given combined therapy, including one case of respiratory failure and circulatory collapse, one oesophageal varices haemorrhage and one cardiac arrest that were all possibly related to sunitinib. The fourth patient died after myocardial infarction.

And 6% of patients given sunitinib alone died, including one cerebrovascular accident that was possibly treatment related, plus single cases of renal failure, oesophageal varices haemorrhage, circulatory collapse, wound infection, ileus and sepsis.

The authors of a linked comment note that the IMPRINT results “strike yet another blow to the concept of vaccine therapy in metastatic renal cell carcinoma” and await findings from the phase III ADAPT trial of sunitinib alone or alongside an autologous dendritic vaccine.

But they emphasize that “[e]ven if a vaccine trial were to have positive results, the bar for first-line therapy in metastatic renal cell carcinoma is likely to rise further soon.”

Sumanta Pal, from the City of Hope Comprehensive Cancer Center in Duarte, California, USA, and co-authors highlight ongoing trials combining agents targeting VEGF and programmed cell death protein 1.

“VEGF–TKIs might even be fully displaced from the front-line setting if superiority of ipilimumab (a CTLA4 inhibitor) plus nivolumab over sunitinib is shown in a phase 3 trial”, they observe.

In addition, the commentators note that the phase II CABOSUN study of first-line sunitinib versus cabozantinib in intermediate- or poor-risk patients with metastases has already met the primary endpoint of improved PFS with the c-Met and VEGF receptor 2 inhibitor cabozantinib.

“If cabozantinib is established as a front-line standard therapy, the relevance of the VEGF–TKI sunitinib in both IMPRINT and ADAPT would be called into question”, they believe.


Rini BI, Stenzl A, Zdrojowy R, et al. IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol; Advance online publication 3 October 2016. DOI:

Pal SK, Agarwal N, Dizman N, Sonpavde G. Vaccine therapy in renal cell carcinoma: attempting to leap over a rising bar.Lancet Oncol; Advance online publication 3 October 2016. DOI:

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