Lymphoma, Hodgkin, Classic; CHL

Disease ID:1047
Name:Lymphoma, Hodgkin, Classic; CHL
Associated with:1 target
3 immuno-relevant ligands
Synonyms
Hodgkin lymphoma | Hodgkin's lymphoma
Database Links
Disease Ontology: DOID:8567
OMIM: 236000

Targets

CIITA

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
brentuximab vedotin
Immuno Disease Comments: Approved drug for HL.
Clinical Use: Brentuximab vedotin is an anti-neoplastic agent used in the treatment of Hodgkin's lymphoma [7] and systemic anaplastic large cell lymphoma. Several clinical trials are evaluating the combination of brentuximab vedotin with immune checkpoint inhibitors, to assess any synergistic effects as a result of dual targeting. Checkpoint inhibitors being investigated in this way include and (both anti-PD-1), and (anti-CTLA4). Brentuximab vedotin + pembrolizumab (NCT02684292) and brentuximab vedotin + nivolumab (NCT03138499) are both Phase 3 studies in patients with relapsed/refractory classical Hodgkin's lymphoma.

Expanded approvals:
In November 2017, the FDA approved brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, following review of results from the Phase 3 ALCANZA trial (NCT01578499) [2]. In March 2018, the FDA approved the use of brentuximab vedotin for the treatment of patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy. This expansion was based on results from the ECHELON-1 clinical trial (NCT01712490) [1,13]. | View clinical data
Bioactivity Comments: Detailed information contained in the covering patent [5] describes in vitro and in vivo activity of the invention, which supports its anti-CD30 action. However, no affinity data is provided for the interaction between the antibody and its molecular target. | View biological activity
nivolumab
Immuno Disease Comments: Approved drug for cHL.
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 [6]. Combination ipilimumab/nivolumab therapy has been FDA approved (2015) for the treatment of patients with BRAF V600 wild-type, unresectable or metastatic melanoma [4,6].

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
AFM13
Immuno Disease Comments: Phase 2 clinical candidate for relapsed/refractory Hodgkin lymphoma- see NCT02321592
Clinical Use: AFM13 is being evaluated in early stage clinical trials for relapsed/refractory Hodgkin lymphoma and cutaneous T cell lymphoma. It is being tested both as a monotherapy and in combination with the anti-PD-1 checkpoint inhibitor (NCT02665650). Click here to link to ClinicalTrials.gov's full list of AFM13 studies. | View clinical data
Bioactivity Comments: Cytotoxicity of AFM13 is CD30-dependent and it does not bind the CD16B isoform [12]. | View biological activity

References

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1. Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M et al.. (2018) Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N. Engl. J. Med., 378 (4): 331-344. [PMID:29224502]

2. FDA. FDA approves Brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma. Accessed on 10/11/2017. Modified on 10/11/2017. fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm584543.htm?utm_campaign=Oncology%2011%2F9&utm_medium=email&utm_source=Eloqua&elqTrackId=06d11c937bec44c79cd3d453daecb608&elq=4d1b00c5aad64538a4ce8e687b3f3786&elqaid=1289&elqat=1&elqCampaignId=770

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. Francisco JA, Risdon G, Wahl AF, Siegall C. (2006) immunotherapy; fusion proteins; antitumor agents; for treatment and prevention of hodgkin's disease. Patent number: US7090843. Assignee: Seattle Genetics, Inc. Priority date: 09/12/2014. Publication date: 15/08/2006.

6. 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]

7. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A et al.. (2015) Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 385 (9980): 1853-62. [PMID:25796459]

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. Reusch U, Burkhardt C, Fucek I, Le Gall F, Le Gall M, Hoffmann K, Knackmuss SH, Kiprijanov S, Little M, Zhukovsky EA. (2014) A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells. MAbs, 6 (3): 728-39. [PMID:24670809]

13. Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. (2013) Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol., 14 (13): 1348-56. [PMID:24239220]