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Renal cell carcinoma

Disease ID:811
Name:Renal cell carcinoma
Associated with:3 targets
3 immuno-relevant ligands
Database Links
Disease Ontology: DOID:4450

Targets

FZD8
References:  6
programmed cell death 1 (CD279)
Comments:  A combination therapy of nivolumab plus ipilimumab was granted FDA approval in April 2018, for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma.
References:  3
Ligand interactions: 
Ligand Comments
nivolumab
A combination therapy of nivolumab plus ipilimumab was granted FDA approval in April 2018 , for the treatment of intermediate or poor risk, previously ...
trophoblast glycoprotein
Role:  Trophoblast glycoprotein 5T4 expression is upregulated in many solid tumour types. The clinical efficacy of targeting 5T4-expressing RCC tumours has been evaluated in Phase 2 clinical trials.
References:  1,5,12-13
Ligand interactions: 
Ligand Comments
anatumomab mafenatox
Phase 2 clinical immuno-oncology candidate for advanced RCC.
naptumomab estafenatox
Phase 2/3 clinical immuno-oncology candidate for advanced RCC.

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
anatumomab mafenatox 12
Immuno Disease Comments: Phase 2 clinical immuno-oncology candidate for advanced RCC.
Clinical Use: Anatumomab mafenatox has completed Phase 2 clinical evaluation in patients with advanced renal cell carcinoma [12]. | View clinical data
naptumomab estafenatox 1,5
Immuno Disease Comments: Phase 2/3 clinical immuno-oncology candidate for advanced RCC.
Clinical Use: Naptumomab estafenatox (ABR-217620) has completed Phase 2/3 clinical trial in patients with advanced renal cell carcinoma (see NCT00420888 which assessed ABR-217620 + plus IFN-α vs. IFN-α monotherapy) [1-2,5]. However, the primary endpoint of showing a prolonged overall survival was not met in this trial. According to the Active Biotech webpage for Anyara, they are planning a trial of Anyara in PD-1 inhibitor-refractory solid cancers. | View clinical data
nivolumab 3,9
Immuno Disease Comments: A combination therapy of nivolumab plus ipilimumab was granted FDA approval in April 2018 , for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma
Clinical Use: In December 2014 nivolumab was approved under the FDA's accelerated approval program for the treatment of advanced (metastatic) melanoma, following review of positive clinical trial results [10]. The FDA expanded nivolumab's approval in 2015 to include treatment of advanced (metastatic) squamous and non-squamous non-small cell lung cancer (NSCLC) in patients with disease progression on or after platinum-based chemotherapy. Nivolumab outperformed standard chemotherapy with , in a randomized, open-label, phase III clinical study in patients with previously treated renal-cell carcinoma [8]. Consequently, in November 2015, FDA approval was extended further to include treatment of advanced renal cell carcinoma in patients who have received prior anti-angiogenic therapy.

Combination therapy with and nivolumab has been reported to exhibit >60% objective-response rate (ORR) in treatment-naive advanced melanoma patients with BRAF wild-type tumours [11] (results from Phase 1 study NCT01927419). This is in comparison to ipilimumab alone which provided only 11% confirmed ORR. These findings have been confirmed by Phase 3 study (NCT01844505) results showing significantly longer progression-free survival in patients given the combination therapy vs. the nivolumab only group [7]. Combination ipilimumab/nivolumab therapy has been FDA approved (2015) for the treatment of patients with BRAF V600 wild-type, unresectable or metastatic melanoma [4,7].

In May 2016, the FDA granted accelerated approval for nivolumab to be used as a therapy for patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation . In November 2016, the FDA further expanded approval to include treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy.

February 2017 saw accelerated approval for locally advanced or metastatic urothelial carcinoma, for those patients with disease progression despite receiving platinum-containing chemotherapy. The accelerated approval programme saw nivolumab's authorisation as a treatment for paediatric patients, 12 years and older, with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, , and , in August 2017. Accelerated approval was granted by the FDA in September 2017 for the treatment of patients with hepatocellular carcinoma who have been previously treated with , based on preliminary results from clinical trial NCT01658878.

A combination therapy of nivolumab plus ipilimumab was granted FDA approval in April 2018 , for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma [3], based on results from the CheckMate 214 trial (NCT02231749) [9]. Later in 2018 (August) the FDA approved nivolumab for patients with metastatic small cell lung cancer (SCLC; with progression after platinum-based chemotherapy and at least one other line of therapy) under their accelerated approval program. | View clinical data

References

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1. Eisen T, Hedlund G, Forsberg G, Hawkins R. (2014) Naptumomab estafenatox: targeted immunotherapy with a novel immunotoxin. Curr Oncol Rep, 16 (2): 370. [PMID:24445502]

2. Elkord E, Burt DJ, Sundstedt A, Nordle Ö, Hedlund G, Hawkins RE. (2015) Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α. Oncotarget, 6 (6): 4428-39. [PMID:25669986]

3. FDA. FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. Accessed on 18/04/2018. Modified on 18/04/2018. www.fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm604685.htm?utm_campaign=Oncology%204%2F16%2F2018&utm_medium=email&utm_source=Eloqua&elqTrackId=461a88586a9a4db284ceb54da34a6a23&elq=8b10e118e0b249beb2807c129fc264e8&elqaid=3169&elqat=1&elqCampaignId=2374

4. FDA. Nivolumab in combination with ipilimumab. Accessed on 17/06/2016. Modified on 17/06/2016. US Food and Drug Administration, http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm465274.htm

5. Hawkins RE, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P et al.. (2016) A Randomized Phase II/III Study of Naptumomab Estafenatox + IFNα versus IFNα in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis. Clin. Cancer Res., 22 (13): 3172-81. [PMID:26851187]

6. Janssens N, Andries L, Janicot M, Perera T, Bakker A. (2004) Alteration of frizzled expression in renal cell carcinoma. Tumour Biol., 25 (4): 161-71. [PMID:15557753]

7. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P et al.. (2015) Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N. Engl. J. Med., 373 (1): 23-34. [PMID:26027431]

8. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER et al.. (2015) Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N. Engl. J. Med., 373 (19): 1803-13. [PMID:26406148]

9. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S et al.. (2018) Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N. Engl. J. Med., 378 (14): 1277-1290. [PMID:29562145]

10. O'Sullivan Coyne G, Madan RA, Gulley JL. (2014) Nivolumab: promising survival signal coupled with limited toxicity raises expectations. J. Clin. Oncol., 32 (10): 986-8. [PMID:24590655]

11. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS et al.. (2015) Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med., 372 (21): 2006-17. [PMID:25891304]

12. Shaw DM, Connolly NB, Patel PM, Kilany S, Hedlund G, Nordle O, Forsberg G, Zweit J, Stern PL, Hawkins RE. (2007) A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma. Br. J. Cancer, 96 (4): 567-74. [PMID:17285137]

13. Stern PL, Harrop R. (2017) 5T4 oncofoetal antigen: an attractive target for immune intervention in cancer. Cancer Immunol. Immunother., 66 (4): 415-426. [PMID:27757559]