kidneys with blood cells surrounding

SRafiqueKidney cancer—also called renal cell cancer (RCC)—is one of the major types of cancer for which immunotherapies are currently in development [ see our Cancer Immunotherapies – 2015 and U.S. Physician and Payer Forum – Immune Checkpoint Inhibitors reports].

On the third day at EMUC 2015, L. Albiges  (FR) and D. McDermott (US) lectured in the session “Kidney cancer: Novel approaches in advanced RCC” where they discussed, respectively, the role of vaccine therapies and immune checkpoint inhibitors for RCC.

The role of the immune system in RCC is well established. Whilst a number of Phase III trials have looked at the role of immunotherapeutic vaccines in RCC, to date, all of these have been negative studies.  L. Albiges pointed towards three negative Phase III trials for RCC (Reniale, Vitespen and TroVax) where immunologic vaccines failed to demonstrate a clinical efficacy benefit. Further, recent data presented at ESMO for IMA901 added to Sutent (Pfizer’s sunitinib) showed that the multipeptide cancer vaccine also failed to demonstrate OS and PFS in the Phase III first-line study (Rini B, 2015).

However, one Phase III trial of a vaccine in RCC is still ongoing. The autologous dendritic cell vaccine AGS-003 is being evaluated in a Phase III trial in combination with Sutent. L. Albiges highlighted the Phase II data where this vaccine demonstrated a PFS of 11.2 months and MOS of 30.2 months with no additive toxicities associated with the combination with Sutent (Amin A, 2015).

If AGS-003 does indeed demonstrate a significant efficacy benefit in its pivotal Phase III study for RCC (primary endpoint: OS), we expect that it may face other challenges due to its administrative approach – i.e. the need to take a tissue sample and the requirement for leukapheresis may be too cumbersome (and therefore potentially not cost-effective)*. With no positive late-phase studies for immunotherapeutic vaccines to date, the Phase III study of AGS-003 in this indication may seal the fate of this drug class in RCC.

By contrast, immune checkpoint inhibitors have demonstrated a role across many tumor types (including RCC) and DRG expects that role to grow in the future. Indeed, Opdivo (BMS/Ono’s nivolumab) is under priority review by the FDA and has been accepted for review by the EMA for pretreated advanced RCC patients. In his lecture, D. McDermott pointed toward the Phase III CheckMate-025 data for Opdivo vs. Afinitor (Novartis’s everolimus) in RCC that was recently presented at ESMO 2015 – where Opdivo demonstrated OS, PFS, and QOL improvements as well as a long duration of response [see Batman (Opdivo) and Robin (Cometriq) come to rescue renal cell carcinoma].

Unlike other tumor types, in RCC it is unclear whether the immune checkpoint inhibitors benefit a subset of patients. Biomarker development in this indication has been challenging with multiple studies indicating that PDL1 expression is not a reliable for predicting responders.

D. McDermott was firm in his view that combining anti-CTLA and anti-PD1 agents is the way forward for RCC – as exemplified by the combination Yervoy (BMS/Ono’s ipilimumab) and Opdivo for melanoma.  The combination attains higher response rates than either agent alone, though the toxicity is higher, and D. McDermott hopes to see a similar story evolve in RCC – despite the growing list of single-agent trials in this disease.

Experts interviewed by Decision Resources Group for the Cancer Immunotherapies – 2015 report tell us:

  • “Vaccines in general haven’t really worked by themselves in a lot of diseases, but it seems to make sense to combine them with drugs like immune checkpoint inhibitors; these types of combinations are scientifically interesting.” – Interviewed oncologist, United States
  • “At the moment, PD-L1 expression has not been verified as a definitive biomarker. Patients should be included in clinical trials regardless of PD-L1 expression, but it’s crucial that these trials test for PD-L1 expression in participants.” – Interviewed oncologist, Japan

Further insight into the clinical development of immunotherapies for RCC (and other oncology indications) can be found in our 2015 report: Cancer Immunotherapies – 2015 For details on how to optimize U.S. market access strategy, see Physician and Payer Forum: Immune Checkpoint Inhibitors in Oncology” with primary market research from physicians and payers.

*Of note, Provenge, another autologous vaccine with the need for leukapheresis, was FDA and EMA approved for metastatic castrate resistant prostate cancer, however, has since been removed from the market.


Rini B, et al. Results from an open-label, randomized, controlled phase 3 study investigating IMA901 multipeptide cancer vaccine in patients receiving sunitinib as first-line therapy for advanced/metastatic RCC. Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract LBA 17

Amin A. et al. Survival with AGS-003, an autologous dendritic cell–based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results. Journal for Immunotherapy of Cancer 2015, 3:14.


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