A randomized phase II study on the OPTimization of Immunotherapy in squamous carcinoma of the head and neck (SCCHN) - OPTIM (AIO-KHT-0117)

A randomized phase II study on the OPTimization of Immunotherapy in squamous carcinoma of the head and neck (SCCHN) - OPTIM (AIO-KHT-0117)

abstracts 1173TiP A randomized phase II study on the OPTimization of Immunotherapy in squamous carcinoma of the head and neck (SCCHN) - OPTIM (AIO-K...

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abstracts

1173TiP

A randomized phase II study on the OPTimization of Immunotherapy in squamous carcinoma of the head and neck (SCCHN) - OPTIM (AIO-KHT-0117)

V. Gru¨nwald1, D. Hahn2, J. Alt3, G. Schuch4, P. Ivanyi5 Clinic for Cancer Research and Clinic for Urology, University Hospital Essen Westdeutsches Tumorzentrum, Essen, Germany, 2Hematology and Oncology, Klinikum Stuttgart - Katharinenhospital Klinik f. Onkologie, Stuttgart, Germany, 3III. Medizinische amatologischKlinik und Poliklinik, Universit€ atsmedizin Mainz, Mainz, Germany, 4H€ Onkologische Praxis Altona (HOPA), H€ amatologisch-Onkologische Praxis Altona 5 (HOPA), Hamburg, Germany, Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany 1

Background: In most SCCHN patients receiving palliative treatment with platinumbased chemotherapy, the tumor eventually progresses and requires further treatment options. PD-1 inhibitor nivolumab was authorized in this setting in 2017 after proving superior to single agent chemotherapy in objective response and overall survival. But there are still patients who progress rapidly with nivolumab monotherapy. In this population, prompt escalation of immunotherapy by adding the CTLA-4 antagonist ipilimumab to nivolumab may be beneficial, as this combined checkpoint blockade has proven superior to nivolumab alone in several tumors. It is not clear, though, if

v474 | Head And Neck Cancer, Excluding Thyroid

combined immunotherapy is superior to chemotherapy in this setting of SCCHN patients responding poorly to nivolumab alone. The OPTIM trial investigates this question. Trial design: 280 patients with recurrent or metastatic SCCHN progressing after platinum-based chemotherapy or within 6 months after RCT will be recruited at 24 German sites. All patients initially receive nivolumab monotherapy according to current prescribing information (240 mg Q2W). They are closely followed for tumor progression by radiologic assessment every 4-6 weeks, i.e. at increased frequency compared to standard of care. Patients who progress during the first 24 weeks of nivolumab monotherapy are randomized 1:1 between intensified immunotherapy (nivolumab 3 mg/kg Q2W þ ipilimumab 1 mg/kg Q6W) and chemotherapy (docetaxel 75 mg/m2 Q3W). 157 patients are planned to be randomized. Patients who do not progress during the first 24 weeks of nivolumab monotherapy continue treatment according to standard of care. After randomization, study treatment continues until disease progress or for up to 12 months. The primary endpoint is overall response rate after randomization, hypothesizing that dual checkpoint blockade improves ORR to 25% compared to 10% with docetaxel. Secondary endpoints are overall survival, progression-free survival, safety, and quality of life. Recruitment started in July 2018 and is ongoing. Clinical trial identification: 2017-003349-14. Legal entity responsible for the study: AIO-Studien-gGmbH, Berlin. Funding: Bristol-Myers Squibb. Disclosure: V. Gru¨nwald: Full / Part-time employment: University Hospital Essen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Cerulean; Advisory / Consultancy, Speaker Bureau / Expert testimony: COCS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: EUSAPharm; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): EISAI; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: MedUpdate; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: MedKomAkademie; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: NewConceptOncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson & Johnson; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: PeerVoice; Advisory / Consultancy, Speaker Bureau / Expert testimony: StreamedUp!; Advisory / Consultancy, Speaker Bureau / Expert testimony: ThinkWired!. All other authors have declared no conflicts of interest.

Volume 30 | Supplement 5 | September 2019

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our previous report and our long experience we are quite comfortable with weekly Cisplatin (in the dose of 40 mg/m2), and hypothesize that weekly Cisplatin (40 mg/m2) times 6-7 is non-inferior to 3 weekly Cisplatin 100 mg/m2 times three (days 1,22,43). Trial design: Multicentric Open labelled, non-inferiority randomized controlled phase III trial. Sample size was calculated expecting 60% LRC (loco-regional control) rate at 2 years in control arm, and 65% in experimental arm, with 80%power of study, alpha error 5%, non-inferiority margin of 10%. Based on these parameters each arm will require143 patients (including 10% lost to follow up/protocol violations etc.). Main Inclusion criteria: Newly diagnosed, chemo/radiotherapy naı¨ve, biopsy or cytology proven, locally advanced head and neck squamous cell carcinoma excluding nasopharyngeal carcinoma (stage III and IV without distant metastases). ARM A: Three weekly Cisplatin100 mg/m2 (Day1, 22, 43) to be started on first day of radiation and given on days 1,22,43 ARM B: Weekly Cisplatin40mg/m2 times 6-7 Primary objective: Loco Regional Control Rate at 2 years. Clinical trial identification: CTRI/2018/03/012422 release date 08/03/2018. Legal entity responsible for the study: Atul Sharma. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Annals of Oncology