This is a phase IB/II trial to examine feasibility and safety of checkpoint blockade (aPD1 with or without aCTLA4) neoadjuvant to standard of care (SOC) in advanced stage head and neck squamous cell carcinoma (HNSCC), a patient population in need for improved clinical outcome and in tumors likely to respond to neoadjuvant aPD1 and aCTLA4. In addition, with this research protocol the potential impact of intratumoral hypoxia on tumor infiltrating lymphocyte (TIL) abundance, differentiation and effector function will be assessed, and the potentially divergent effects of T cell checkpoint blockade in areas of hypoxia and normoxia.
The phase Ib is designed as 3 + 3, with primary objective feasibility and toxicity. Of Note: endpoints must be reached in all 6 patients of cohort 1 and 2, before start of the next cohort. The phase II is designed as a single arm design with primary endpoint efficacy. In phase Ib, two cohorts will be used (cohort 1: nivolumab only and cohort 2: nivolumab and ipilimumab neoadjuvant to surgery) to define which neoadjuvant immunotherapy regimen will be taken towards the expansion cohort 3. Thirty-two patients will be treated with nivolumab (240 mg flat dose, week 1 and week 3, twice in total) as a single agent OR the combination of ipilimumab (1 mg/kg) + nivolumab (240mg flat dose) in week 1, and nivolumab 240mg flat dose in week 3, neoadjuvant to SOC (surgery with or without adjuvant (C)RT).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Nivolumab (240 mg flat dose, week 1 and week 3, twice in total) monotherapy, neoadjuvant to SOC (surgery with or without adjuvant (C)RT).
Ipilimumab (1 mg/kg) only in week 1, in combination with nivolumab (240 mg flat dose, week 1 and week 3, twice in total), neoadjuvant to SOC (surgery with or without adjuvant (C)RT).
NKI-AVL
Amsterdam, North Holland, Netherlands
Phase Ib: the number of patients that will not endure a delay in surgery due to neoadjuvant immunotherapy related toxicity OR toxicity due to the treatment of immunotherapy related toxicity.
Time frame: 2.5 years
Phase II: Tumor response to neoadjuvant IT in terms of tumor tissue pathological response at time of surgery compared to RECIST 1.1 (FDG-PET and perfusion and diffusion weighted MRI).
Time frame: 2.5 years
Phase Ib/II: the potential impact of local tumor hypoxia on tumor T-cell abundance and capacity before and after neo-adjuvant immunotherapy, through HX4-PET-guided tumor biopsies from hypoxic and normoxic tumor regions.
Time frame: 2.5 years
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