Clinical Trial Protocol

Phase III study of nivolumab alone or combined with ipilimumab as immunotherapy versus standard of care in resectable head and neck squamous cell carcinoma

Department of Otorhinolaryngology & Head & Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Nikolaus Moeckelmann

Department of Otorhinolaryngology & Head & Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Arne Boettcher

Department of Otorhinolaryngology & Head & Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Adrian Muenscher

Department of Otorhinolaryngology & Head & Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Mascha Binder

Department of Internal Medicine IV, University Medical Center Halle (Saale), Germany

Search for more papers by this author

Eik Vettorazzi

Department of Medical Biometry & Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Carsten Bokemeyer

Department of Medical Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Philippe Schafhausen

Department of Medical Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Christian S Betz

Department of Otorhinolaryngology & Head & Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Chia-Jung Busch

*Author for correspondence: Tel.: +49 407 4105 2360;

E-mail Address: cjbusch@uke.de

https://orcid.org/0000-0001-8254-8237

Department of Otorhinolaryngology & Head & Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Search for more papers by this author

Published Online:9 Sep 2020https://doi.org/10.2217/fon-2020-0595

View article

Abstract

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) often requires postoperative chemoradiation with high risk of toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining nivolumab (N), a PD-1-inhibitor and ipilimumab (I), a CTLA4- inhibitor, may improve DFS due to antitumor effects of immunotherapy. The IMSTAR-HN study compares neoadjuvant N and N ± I 6 months after adjuvant therapy versus standard therapy as first-line treatment for LA-HNSCC. Eligible patients have treatment-naive LA-HNSCC, Eastern cooperative oncology group performance score (PS) ≤1 and no distant metastasis. 276 patients will be randomized into two arms. Primary endpoint is DFS and secondary endpoint includes locoregional control (LRC) and overall survival (OS). This study is one of the first in HNSCCs implementing immunotherapy in first-line treatment in a curative setting.

Clinical Trial Registration: NCT03700905 (ClinicalTrials.gov)

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J. Clin. 61(2), 69–90 (2011).
MedlineGoogle Scholar
2. Ragin CC, Modugno F, Gollin SM. The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J. Dent. Res. 86(2), 104–114 (2007).
Medline CASGoogle Scholar
3. Gold KA, Lee HY, Kim ES. Targeted therapies in squamous cell carcinoma of the head and neck. Cancer 115(5), 922–935 (2009).
Medline CASGoogle Scholar
4. Bernier J, Domenge C, Ozsahin M et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N. Engl. J. Med. 350(19), 1945–1952 (2004). • Landmark study of the European Organization for research and treatment of cancer defining risks factors for adjuvant radiochemotherapy in head-and-neck squamous cell carcinoma (HNSCC).
Medline CASGoogle Scholar
5. Bernier J, Cooper JS, Pajak TF et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501). Head Neck 27(10), 843–850 (2005). •• Summarizes role of adjuvant treatment in head-and-neck cancer.
MedlineGoogle Scholar
6. Cooper JS, Pajak TF, Forastiere AA et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 350(19), 1937–1944 (2004). • Landmark study of the radiation therapy oncology group (RTOG) defining risks factors for adjuvant radiochemotherapy in HNSCC.
MedlineGoogle Scholar
7. Ferris RL, BlumenscheinGJr, Fayette J et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 375(19), 1856–1867 (2016). •• Pivotal Phase III trial results that resulted in approval of nivolumabmab for the treatment of recurrent and/or metastatic HNSCC.
MedlineGoogle Scholar
8. Cohen EEW, Bell RB, Bifulco CB et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J. Immunother. Cancer 7(1), 184 (2019).
MedlineGoogle Scholar
9. Hanna GJ, Adkins DR, Zolkind P, Uppaluri R. Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma. Oral Onco. 73, 65–69 (2017). •• Findings of neoadjuvant immunotherapy in HNSCC indicating that neoadjuvant treatment is well tolerated and does not delay surgery in patients with head and neck cancer.
MedlineGoogle Scholar
10. Chaft JE, Forde PM, Smith KN et al. Neoadjuvant nivolumab in early-stage, resectable non-small cell lung cancers. J. Clin. Oncol. 35(Suppl. 15), 8508–8508 (2017).
Google Scholar
11. Ferris RL, Gonçalves A, Baxi SS et al. LBA46An open-label, multicohort, Phase I/II study in patients with virus-associated cancers (CheckMate 358): safety and efficacy of neoadjuvant nivolumab in squamous cell carcinoma of the head and neck (SCCHN). Ann. Oncol. 28(Suppl. 5), v605–v649 (2017). • Preliminary safety and efficacy data concerning neoadjuvant use of nivolumab in HNSCC.
Google Scholar
12. Uppaluri R, Zolkind P, Lin T et al. Neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV negative head and neck squamous cell carcinoma (HNSCC). J. Clin. Oncol. 35(Suppl. 15), 6012–6012 (2017). • Preliminary safety and efficacy data concerning neoadjuvant use of pembrolizumab in HNSCC.
Google Scholar
13. Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373(1), 23–34 (2015).
Medline CASGoogle Scholar
14. Escudier B, Tannir NM, McDermott DF et al. LBA5CheckMate 214: efficacy and safety of nivolumab+ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. Ann. Oncol. 28(Suppl. 5), v605– v649 (2017).
Google Scholar
15. Bjordal K, Kaasa S. Psychometric validation of the EORTC core quality of life questionnaire, 30-item version and a diagnosis-specific module for head and neck cancer patients. Acta Oncol. 31(3), 311–321 (1992).
Medline CASGoogle Scholar
16. Bjordal K, Ahlner-Elmqvist M, Tollesson E et al. Development of a European Organization for Research and Treatment of Cancer (EORTC) questionnaire module to be used in quality of life assessments in head and neck cancer patients. EORTC quality of life study group. Acta Oncol. 33(8), 879–885 (1994).
Medline CASGoogle Scholar
17. Singer S, Araujo C, Arraras JI et al. Measuring quality of life in patients with head and neck cancer: update of the EORTC QLQ-H&N module, Phase III. Head Neck 37(9), 1358–1367 (2014).
MedlineGoogle Scholar

Vol. 16, No. 36

Metrics

Downloaded 676 times

History

Received 9 June 2020

Accepted 10 August 2020

Published online 9 September 2020

Published in print December 2020

Information

Keywords

Author contributions

All co-author participated sufficiently in the work and made substantial contributions to the conception and design of the work; drafted the work or revised it critically for important intellectual content; did final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial & competing interests disclosure

This trial was conducted as an investigator sponsored trial and financial support was received from Bristol-Myers Squibb. CS Betz received honoraria, travel, accomodations and other expenses from Brainlab AG, Merck, Nanobiotix and Bristol-Myers Squibb. CS Betz has been paid for consulting and advisory role by Brainlab AG, Merck, Nanobiotix, Bristol-Myers Squibb and Sanofi-Aventis. M Binder received honoraria, travel, accomodations and other expenses from Bristol-Myers Squibb, Merck, Merck Sharp & Dohme, Sanofi, Hexal, Roche, Celgene and Takeda. M Binder has been paid for consulting and advisory role by Roche, Hexal, Takeda and Bristol-Myers Squibb. A Boettcher has received grants for training and speaker honoraria from Inspire Medical Systems, Inc., as well as training grants from APrevent Biotech GmbH. C Bokemeyer reports personal fees from Sanofi Aventis, Merck KgA, Bristol-Myers Squibb, Merck Sharp & Dohme, Lilly Imclone, Bayer Healthcare, GSO Contract Research, AOK Rheinland-Hamburg and Novartis outside the submitted work. C-J Busch and P Schafhausen received honoraria, travel, accomodations and other expenses from Bristol-Myers Squibb, Merck and Merck Sharp & Dohme. They have been paid for consulting and advisory role by Bristol-Myers Squibb, Merck and Merck Sharp & Dohme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

PDF download