Nivolumab (NIVO) alone or with ipilimumab (COMBO) immune checkpoint blockade (ICB) prior to curative surgery has shown promising results in multiple tumor types. We completed a phase Ib/II study with neoadjuvant NIVO or COMBO in resectable head and neck squamous cell carcinoma (HNSCC) and show safety, efficacy and correlative biomarker results.
32 stage II-IVB HNSCC patients indicated for curative (salvage) surgery were treated with NIVO (240mg, weeks 1&3, N=6) or NIVO (240mg, weeks 1&3) + IPI (1mg/kg, week 1, N=26) prior to surgery in week 5. Imaging was performed at baseline and week 4. AEs were reported in terms of CTCAE. Pathological response (pR) was defined as % change in viable tumor cells from baseline to on-treatment; ≥90% pR was considered (near-) complete response (pCR). WES and RNAseq were performed on paired tumor biopsies.
32 (31 HPV-negative) patients started treatment (stage II n=3, III n=8, IVA-B n=11, recurrent disease n=10). 6 patients included with recurrent disease had had previous (C)RT. 1 patient discontinued ICB after one course due to patient’s preference. Surgery was not postponed in any patient. 3/32 patients did not undergo surgery: 1 due to unresectable PD and 2 due to reasons unrelated to ICB or disease. Grade 3-4 irAEs in 11/32 patients were well manageable. (Near-)pCR in the primary tumor was seen in 9/29 evaluable patients (31%). Another 31% of patients had 20-89% pR. At 14 months median FU, RFS for patients with (near-)pCR was 100%, significantly better than patients with <90% pR (p=<0.05). Metabolic response assessment with FDG-PET (week 4) was able to identify (near-)pCRs. A baseline AID/APOBEC-associated tumor mutational profile was correlated with (near)pCR (p=<0.05). Finally, (near)pCR tumors were characterized by a decrease in hypoxia gene expression after ICB.
Neoadjuvant ICB was feasible in HNSCC and induced (near)pCR in 31% of evaluable patients at time of surgery, which was accompanied by 100% RFS. Baseline AID/APOBEC-related mutations, on-treatment FDG-PET and resolution of hypoxia need future validation to discover their potential role as biomarkers for (near)pCR after ICB in HNSCC.
NCT03003637.
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital.
Bristol Myers-Squibb.
L. Zuur: Spouse/Financial dependant: Mosadex U.A.; Spouse/Financial dependant: Obvious Pharmaceuticals BV. M.W. van den Brekel: Research grant/Funding (institution), Travel/Accommodation/Expenses: ATOS Medical. S.M. Willems: Research grant/Funding (institution): Roche; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Nextcure. T.N. Schumacher: Full/Part-time employment: Kite Pharma; Leadership role: Kite Pharma; Shareholder/Stockholder/Stock options: AIMM Therapeutics; Shareholder/Stockholder/Stock options: Allogene; Shareholder/Stockholder/Stock options: Merus; Shareholder/Stockholder/Stock options: Kite Pharma; Shareholder/Stockholder/Stock options: Neon Therapeutics; Shareholder/Stockholder/Stock options: Neogene Therapeutics; Shareholder/Stockholder/Stock options: Scenic Biotech; Advisory/Consultancy: AIMM Therapeutics; Advisory/Consultancy: Allogene; Advisory/Consultancy: Merus; Advisory/Consultancy: Neon Therapeutics; Advisory/Consultancy: Neogene Therapeutics; Advisory/Consultancy: Scenic Biotech; Research grant/Funding (self): Merck KgGA; Research grant/Funding (self): MSD; Licensing/Royalties: Kite Pharma; Licensing/Royalties: Neon Therapeutics; Licensing/Royalties: Scenic Biotech; Licensing/Royalties: Immatics. C.U. Blank: Honoraria (self), Paid to the institute: BMS; Honoraria (self), Paid to the institute: MSD; Honoraria (self), Paid to the institute: Roche; Honoraria (self), Paid to the institute: Novartis; Honoraria (self), Paid to the institute: GSK; Honoraria (self), Paid to the institute: AZ; Honoraria (self), Paid to the institute: Pfizer; Honoraria (self), Paid to the institute: Lilly; Honoraria (self), Paid to the institute: Genmab; Honoraria (self), Paid to the institute: Pierre Fabre; Honoraria (self), Paid to CUB: Third Rock Ventures; Shareholder/Stockholder/Stock options: Uniti Cars; Shareholder/Stockholder/Stock options: Immagene BV; Research grant/Funding (self), Paid to the institute: BMS; Research grant/Funding (self), Paid to the institute: Novartis; Research grant/Funding (self), Paid to the institute: NanoString. J.P. de Boer: Advisory/Consultancy: MSD; Research grant/Funding (self), Paid to the institute: Merck KgGa; Travel/Accommodation/Expenses: MSD. J.B.A.G. Haanen: Shareholder/Stockholder/Stock options: Neogene Therapeutics; Research grant/Funding (institution): BMS; Research grant/Funding (institution): MSD; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Neon. All other authors have declared no conflicts of interest.