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Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Checkpoint Inhibitors | Meeting report

The “Great Debate” at Immunotherapy Bridge 2020, December 3rd, 2020

Authors: Paolo A. Ascierto, Joshua Brody, Lisa H. Butterfield, Olivera J. Finn, John Goldberg, Francesco Perrone, Ryan J. Sullivan, Bernard A. Fox, Patrick Hwu, Igor Puzanov

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

As part of the 2020 Immunotherapy Bridge virtual congress (December 2nd–3rd, Italy), the Great Debate session featured counterpoint views from leading experts on three clinical questions in immunotherapy today. The first of these was whether antitumoral vaccination is still a treatment option. The second topic debated whether anti-programmed death (PD)-1/PD-ligand (L)1 blockade should be the backbone for immunotherapy combination. Finally, the use of innovative study designs and surrogate endpoints was considered from both an academic and industry perspective. For each topic, two experts presented the argument and counter-argument in support of two different points of view. As with previous Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their respective personal view. The views summarised in this article are based on available evidence but may reflect personal interpretation of these data, clinical experience and subjective opinion of the speaker.
Literature
1.
go back to reference Hu Z, Ott PA, Wu CJ. Towards personalized, tumor-specific, therapeutic vaccines for cancer. Nat Rev Immunol. 2018;18(3):168–82.CrossRef Hu Z, Ott PA, Wu CJ. Towards personalized, tumor-specific, therapeutic vaccines for cancer. Nat Rev Immunol. 2018;18(3):168–82.CrossRef
2.
go back to reference Wells DK, van Buuren MM, Dang KK, Hubbard-Lucey VM, Sheehan KCF, et al. Key parameters of tumor epitope immunogenicity revealed through a consortium approach improve neoantigen prediction. Cell. 2020;183(3):818-834.e13.CrossRef Wells DK, van Buuren MM, Dang KK, Hubbard-Lucey VM, Sheehan KCF, et al. Key parameters of tumor epitope immunogenicity revealed through a consortium approach improve neoantigen prediction. Cell. 2020;183(3):818-834.e13.CrossRef
3.
go back to reference Butterfield LH, Vujanovic L, Santos PM, Maurer DM, Gambotto A, Lohr J, et al. Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma. J Immunother Cancer. 2019;7(1):113.CrossRef Butterfield LH, Vujanovic L, Santos PM, Maurer DM, Gambotto A, Lohr J, et al. Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma. J Immunother Cancer. 2019;7(1):113.CrossRef
4.
go back to reference Santos PM, Adamik J, Howes TR, Du S, Vujanovic L, Warren S, et al. Impact of checkpoint blockade on cancer vaccine-activated CD8+ T cell responses. J Exp Med. 2020;217(7):e20191369.CrossRef Santos PM, Adamik J, Howes TR, Du S, Vujanovic L, Warren S, et al. Impact of checkpoint blockade on cancer vaccine-activated CD8+ T cell responses. J Exp Med. 2020;217(7):e20191369.CrossRef
5.
go back to reference Maurer DM, Adamik J, Santos PM, Shi J, Shurin MR, Kirkwood JM, et al. Dysregulated NF-κB-dependent ICOSL expression in human dendritic cell vaccines impairs T-cell responses in patients with melanoma. Cancer Immunol Res. 2020;8(12):1554–67.CrossRef Maurer DM, Adamik J, Santos PM, Shi J, Shurin MR, Kirkwood JM, et al. Dysregulated NF-κB-dependent ICOSL expression in human dendritic cell vaccines impairs T-cell responses in patients with melanoma. Cancer Immunol Res. 2020;8(12):1554–67.CrossRef
6.
go back to reference Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565(7738):234–9.CrossRef Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565(7738):234–9.CrossRef
7.
go back to reference Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020;585(7823):107–12.CrossRef Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020;585(7823):107–12.CrossRef
8.
go back to reference Finn OJ. The dawn of vaccines for cancer prevention. Nat Rev Immunol. 2018;18(3):183–94.CrossRef Finn OJ. The dawn of vaccines for cancer prevention. Nat Rev Immunol. 2018;18(3):183–94.CrossRef
9.
go back to reference Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15(17):5323–37.CrossRef Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15(17):5323–37.CrossRef
10.
go back to reference Tan AC, Goubier A, Kohrt HE. A quantitative analysis of therapeutic cancer vaccines in phase 2 or phase 3 trial. J Immunother Cancer. 2015;3:48.CrossRef Tan AC, Goubier A, Kohrt HE. A quantitative analysis of therapeutic cancer vaccines in phase 2 or phase 3 trial. J Immunother Cancer. 2015;3:48.CrossRef
11.
go back to reference Rini BI, Stenzl A, Zdrojowy R, Kogan M, Shkolnik M, Oudard S, 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. 2016;17(11):1599–611.CrossRef Rini BI, Stenzl A, Zdrojowy R, Kogan M, Shkolnik M, Oudard S, 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. 2016;17(11):1599–611.CrossRef
12.
go back to reference Mittendorf EA, Lu B, Melisko M, Price Hiller J, Bondarenko I, Brunt AM, et al. Efficacy and safety analysis of nelipepimut-S vaccine to prevent breast cancer recurrence: a randomized, multicenter, phase III clinical trial. Clin Cancer Res. 2019;25(14):4248–54.CrossRef Mittendorf EA, Lu B, Melisko M, Price Hiller J, Bondarenko I, Brunt AM, et al. Efficacy and safety analysis of nelipepimut-S vaccine to prevent breast cancer recurrence: a randomized, multicenter, phase III clinical trial. Clin Cancer Res. 2019;25(14):4248–54.CrossRef
13.
go back to reference Gulley JL, Borre M, Vogelzang NJ, Ng S, Agarwal N, Parker CC, et al. Phase III trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(13):1051–61.CrossRef Gulley JL, Borre M, Vogelzang NJ, Ng S, Agarwal N, Parker CC, et al. Phase III trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(13):1051–61.CrossRef
14.
go back to reference Berzofsky JA, Terabe M, Wood LV. Strategies to use immune modulators in therapeutic vaccines against cancer. Semin Oncol. 2012;39(3):348–57.CrossRef Berzofsky JA, Terabe M, Wood LV. Strategies to use immune modulators in therapeutic vaccines against cancer. Semin Oncol. 2012;39(3):348–57.CrossRef
15.
go back to reference Kimura T, McKolanis JR, Dzubinski LA, Islam K, Potter DM, Salazar AM, et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila). 2013;6(1):18–26.CrossRef Kimura T, McKolanis JR, Dzubinski LA, Islam K, Potter DM, Salazar AM, et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila). 2013;6(1):18–26.CrossRef
16.
go back to reference Arance Fernandez AM, O’Day SJ, de la Cruz ML, Petrella T, Jamal R, Ny L, et al. Lenvatinib (len) plus pembrolizumab (pembro) for advanced melanoma (MEL) that progressed on a PD-1 or PD-L1 inhibitor: initial results of LEAP-004. Ann Oncol. 2020;31(suppl_4):S1142–215. Arance Fernandez AM, O’Day SJ, de la Cruz ML, Petrella T, Jamal R, Ny L, et al. Lenvatinib (len) plus pembrolizumab (pembro) for advanced melanoma (MEL) that progressed on a PD-1 or PD-L1 inhibitor: initial results of LEAP-004. Ann Oncol. 2020;31(suppl_4):S1142–215.
17.
go back to reference Hong DS, Kurzrock R, Wheler JJ, et al. Phase I dose-escalation study of the multikinase inhibitor lenvatinib in patients with advanced solid tumors and in an expanded cohort of patients with melanoma. Clin Cancer Res. 2015;21(21):4801–10.CrossRef Hong DS, Kurzrock R, Wheler JJ, et al. Phase I dose-escalation study of the multikinase inhibitor lenvatinib in patients with advanced solid tumors and in an expanded cohort of patients with melanoma. Clin Cancer Res. 2015;21(21):4801–10.CrossRef
18.
go back to reference Hong DS, Kurzrock R, Falchook GS, et al. Phase 1b study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma. Oncotarget. 2015;6(40):43127–34.CrossRef Hong DS, Kurzrock R, Falchook GS, et al. Phase 1b study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma. Oncotarget. 2015;6(40):43127–34.CrossRef
19.
go back to reference Sheng X, Yan X, Chi Z, Si L, Cui C, Tang B, et al. Overall survival and biomarker analysis of a phase Ib combination study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) with axitinib in patients with metastatic mucosal melanoma. J Clin Oncol. 2020;38(15_suppl):10007.CrossRef Sheng X, Yan X, Chi Z, Si L, Cui C, Tang B, et al. Overall survival and biomarker analysis of a phase Ib combination study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) with axitinib in patients with metastatic mucosal melanoma. J Clin Oncol. 2020;38(15_suppl):10007.CrossRef
20.
go back to reference Olson D, Luke JJ, Poklepovic AS, Bajaj M, Higgs E, Carll TC, et al. Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial. J Clin Oncol. 2020;38(15_suppl):10004.CrossRef Olson D, Luke JJ, Poklepovic AS, Bajaj M, Higgs E, Carll TC, et al. Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial. J Clin Oncol. 2020;38(15_suppl):10004.CrossRef
21.
go back to reference Da Silva IP, Ahmed T, Lo S, Reijers ILM, Weppler A, Warner AB, et al. Ipilimumab (IPI) alone or in combination with anti-PD-1 (IPI+PD1) in patients (pts) with metastatic melanoma (MM) resistant to PD1 monotherapy. J Clin Oncol. 2020;38(15_suppl):10005.CrossRef Da Silva IP, Ahmed T, Lo S, Reijers ILM, Weppler A, Warner AB, et al. Ipilimumab (IPI) alone or in combination with anti-PD-1 (IPI+PD1) in patients (pts) with metastatic melanoma (MM) resistant to PD1 monotherapy. J Clin Oncol. 2020;38(15_suppl):10005.CrossRef
22.
go back to reference Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.CrossRef Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.CrossRef
23.
go back to reference Dickinson MJ, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, et al. CD20-TCB in relapsed or refractory non-hodgkin lymphoma: durable complete responses and manageable safety observed at clinically relevant doses in phase i dose escalation. EHA Library. 2020;290:S241. Dickinson MJ, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, et al. CD20-TCB in relapsed or refractory non-hodgkin lymphoma: durable complete responses and manageable safety observed at clinically relevant doses in phase i dose escalation. EHA Library. 2020;290:S241.
24.
go back to reference Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S, et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019;25(5):814–24.CrossRef Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S, et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019;25(5):814–24.CrossRef
25.
go back to reference Beatty GL, O’Dwyer PJ, Clark J, Shi JG, Bowman KJ, Scherle PA, et al. First-in-human phase I study of the oral inhibitor of indoleamine 2,3-dioxygenase-1 epacadostat (INCB024360) in patients with advanced solid malignancies. Clin Cancer Res. 2017;23(13):3269–76.CrossRef Beatty GL, O’Dwyer PJ, Clark J, Shi JG, Bowman KJ, Scherle PA, et al. First-in-human phase I study of the oral inhibitor of indoleamine 2,3-dioxygenase-1 epacadostat (INCB024360) in patients with advanced solid malignancies. Clin Cancer Res. 2017;23(13):3269–76.CrossRef
26.
go back to reference Hamid O, Gajewski TF, Frankel AE, Maleski J, Jones MJ, Gangadhar TC, et al. Epacadostat plus pembrolizumab in patients with advanced melanoma: Phase 1 and 2 efficacy and safety results from ECHO-202/KEYNOTE-037. Ann Oncol. 2017;28(Suppl 5):v428–9.CrossRef Hamid O, Gajewski TF, Frankel AE, Maleski J, Jones MJ, Gangadhar TC, et al. Epacadostat plus pembrolizumab in patients with advanced melanoma: Phase 1 and 2 efficacy and safety results from ECHO-202/KEYNOTE-037. Ann Oncol. 2017;28(Suppl 5):v428–9.CrossRef
27.
go back to reference Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, et al. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019;20(8):1083–97.CrossRef Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, et al. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019;20(8):1083–97.CrossRef
28.
go back to reference Park JJH, Siden E, Zoratti MJ, Dron L, Harari O, Singer J, et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials. 2019;20(1):572.CrossRef Park JJH, Siden E, Zoratti MJ, Dron L, Harari O, Singer J, et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials. 2019;20(1):572.CrossRef
29.
go back to reference Prasad V, Kim C, Burotto M, Vandross A. The strength of association between surrogate end points and survival in oncology: a systematic review of trial-level meta-analyses. JAMA Intern Med. 2015;175(8):1389–98.CrossRef Prasad V, Kim C, Burotto M, Vandross A. The strength of association between surrogate end points and survival in oncology: a systematic review of trial-level meta-analyses. JAMA Intern Med. 2015;175(8):1389–98.CrossRef
30.
go back to reference Beaver JA, Howie LJ, Pelosof L, Kim T, Liu J, Goldberg KB, et al. A 25-year experience of us food and drug administration accelerated approval of malignant hematology and oncology drugs and biologics: a review. JAMA Oncol. 2018;4(6):849–56.CrossRef Beaver JA, Howie LJ, Pelosof L, Kim T, Liu J, Goldberg KB, et al. A 25-year experience of us food and drug administration accelerated approval of malignant hematology and oncology drugs and biologics: a review. JAMA Oncol. 2018;4(6):849–56.CrossRef
31.
go back to reference Davis C, Naci H, Gurpinar E, Poplavska E, Pinto A, Aggarwal A. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009–13. BMJ. 2017;359:j4530.CrossRef Davis C, Naci H, Gurpinar E, Poplavska E, Pinto A, Aggarwal A. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009–13. BMJ. 2017;359:j4530.CrossRef
32.
go back to reference Mushti SL, Mulkey F, Sridhara R. Evaluation of overall response rate and progression-free survival as potential surrogate endpoints for overall survival in immunotherapy trials. Clin Cancer Res. 2018;24(10):2268–75.CrossRef Mushti SL, Mulkey F, Sridhara R. Evaluation of overall response rate and progression-free survival as potential surrogate endpoints for overall survival in immunotherapy trials. Clin Cancer Res. 2018;24(10):2268–75.CrossRef
33.
go back to reference Chowdhury S, Mainwaring P, Zhang L, Mundle S, Pollozi E, Gray A, Wildgust M. Systematic review and meta-analysis of correlation of progression-free survival-2 and overall survival in solid tumors. Front Oncol. 2020;14(10):1349.CrossRef Chowdhury S, Mainwaring P, Zhang L, Mundle S, Pollozi E, Gray A, Wildgust M. Systematic review and meta-analysis of correlation of progression-free survival-2 and overall survival in solid tumors. Front Oncol. 2020;14(10):1349.CrossRef
Metadata
Title
The “Great Debate” at Immunotherapy Bridge 2020, December 3rd, 2020
Authors
Paolo A. Ascierto
Joshua Brody
Lisa H. Butterfield
Olivera J. Finn
John Goldberg
Francesco Perrone
Ryan J. Sullivan
Bernard A. Fox
Patrick Hwu
Igor Puzanov
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-02811-8

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