871P - Randomized phase II trial of nivolumab plus paclitaxel in subjects with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) unable for cisplatin (CP)-based chemotherapy (CT): NIVOTAX TTCC study

Background

Up to 20% of patients (pts) with R/M HNSCC who may need CT + antiPD1 are ineligible for CP. NIVOTAX evaluated the efficacy and safety of nivolumab + paclitaxel (N) in pts with untreated R/M HNSCC ineligible for CP-based CT.

Methods

NIVOTAX is a randomized, non-comparative, open-label, multicenter, phase II trial for previously untreated R/M HNSCC pts CP-based CT ineligible. Randomization was 2:1 to Paclitaxel 80 mg/m2/w up to 12 w + Nivolumab 240 mg/q2w or Cetuximab 250 mg/m2/w, followed by maintenance Nivolumab 480 mg/q4w or Cetuximab/w. Pts were stratified by Karnofsky performance status (KPS) 70% vs ≥80%; PD-L1 CPS ≥1 vs <1; and HPV positivity (+). The primary endpoint was 2-year overall survival (2yOS). A 26% 2yOS rate was assumed for the N arm compared to expected 16% with E (10% gain).

Results

From Jun-2020 to Nov-2021, 141 pts were randomized: 93 to N and 48 to E (57% unfit for CP, 27% CP refractory and 16% cumulative CP dose ≥225mg/m2). Pts characteristics were similar in both arms. Median age 65 years, male (77%), smokers (79%), KPS 70% (36%), PD-L1 CPS ≥1 (78%) and HPV+ (4%). Median follow-up was 12.1 months (m) (26.7 for alive pts). 2yOS was 24.7% (95% confidence interval [95% CI], 15.9-33.5) in N vs 13.4% (3.6-23.2) in E. Median OS, progression free survival (PFS) and overall response rate (ORR) (95% CI) in N and E arms were: 12.2 (9.4-15.0) vs 12.1 (10.5-13.7) m; 5.6 (3.5-7.6) vs 5.3 (2.3-8.3) m; and 37.6% (27.8-47.5) vs 37.5% (23.8-51.2), respectively. Early discontinuation (<12 weeks) occurred in 17 pts (12%): 15 (16%) and 2 (4%) in the N and E arms, respectively. Out of the 17, 12 died, all in N arm: 7 respiratory events (1 COVID 19-related); 3 disease progression, 1 hemorrhage, 1 enolic encephalopathy; none deemed treatment-related. There were no toxicity differences between arms except for rash (16/64%); 55/58% of pt had AEs G>=3 and 12% pt in N had immune-mediated AEs.

Conclusions

A 10% increase in 2yOS was reached in the N arm vs E, although rates were lower than expected. While efficacy outcomes were similar, increased respiratory AEs in the N arm led to higher early discontinuation and mortality. COVID19 pandemic may have contributed on these events.

Clinical trial identification

EudraCT 2019-002922-60 NCT04282109.

Editorial acknowledgement

Authors thanks Juan Luis Sanz (APICES) for his editorial assistance.

Legal entity responsible for the study

Grupo Español de Tratamiento de Tumores de Cabeza y Cuello (TTCC).

Funding

Bristol Myers Squibb.

Disclosure

L. Iglesias Docampo: Financial Interests, Personal, Invited Speaker: MercK, Roche, Eisai; Financial Interests, Personal, Advisory Board: MSD, BMS, Bayer, Ipsen, Lilly. N. Baste Rotllan: Non-Financial Interests, Advisory Role: Eisai, MSD, Merck Serono, BioNTech, Roche, BMS, Exelixis. M. Oliva Bernal: Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Financial Interests, Personal, Advisory Board: Merck, MSD; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Invited Speaker, Teaching activities: MSD, Merck; Financial Interests, Personal, Other, IDMC: Transgene; Financial Interests, Personal and Institutional, Funding: Roche; Financial Interests, Institutional, Local PI: ALX Oncology, MSD, ISA Therapeutics BV, Roche, Ayala Therapeutics, Abbvie, Bayer, Boehringer Ingelheim, Merck, Debiopharm, Seagen, Gilead, Beigene, NYKODE; Financial Interests, Institutional, Funding: GSK; Non-Financial Interests, Institutional, Product Samples: Roche. A. Carral Maseda: Financial Interests, Personal, Advisory Board: Amgen, Bayer, BMS, Servier, Merck KGaA; Financial Interests, Personal, Invited Speaker: Grunenthal, Kyowa Kirin, Lilly, Novartis, Pierre Fabre, Sanofi, MSD; Financial Interests, Institutional, Local PI: G1 Therapeutics, Pierre Fabre, BMS; Non-Financial Interests, Member of Board of Directors: TTCC. A. Medina Colmenero: Financial Interests, Personal, Invited Speaker: Ipsen, MSD, Merck; Financial Interests, Personal, Advisory Board: MSD. B. Cirauqui Cirauqui: Financial Interests, Personal, Other, Training grant: MSD, BMS, Merck; Financial Interests, Personal, Invited Speaker: BMS, Merck, MSD; Financial Interests, Personal, Advisory Board: BMS, MSD, Merck; Non-Financial Interests, Member, Board of directors: TTCC group; Non-Financial Interests, Member: GEICAM, SOLTI, SEOM. V. Arrazubi Arrula: Financial Interests, Personal, Invited Speaker: BMS, Lilly, Beigene, Organon; Financial Interests, Personal, Advisory Board: Bristol, MSD. J. Martinez Trufero: Financial Interests, Personal, Advisory Board, Advisory Board meeting: Pharmamar, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Eisai, Merck, Medicamenta, MSD, Ipsen; Financial Interests, Personal, Advisory Board, Advisory Board Meeting: GSK, Deciphera, Boehringer Ingelheim, Eisai; Financial Interests, Personal, Other, Meeting travel expenses: Roche, PharmaMar; Financial Interests, Institutional, Local PI, Clinical trial: Rain Therapeutics, Blueprint, Lilly, Kariopharm Therapeutics, Syneos Health, Boehringer Ingelheim, Ayala Pharmaceuticals, SynOx Therapeutics, BioNTech, Daiichi Sankyo; Non-Financial Interests, Member of Board of Directors, Spanish group of Sarcoma Research: GEIS Group; Non-Financial Interests, Member of Board of Directors, Spanish Group of Head and Neck cancer Research: TTCC Group. J. Rubió-Casadevall: Financial Interests, Personal, Advisory Board, Advisory board meeting in 2021: Sanofi; Financial Interests, Personal, Advisory Board, Participation in advisory board march 2022: Merck; Financial Interests, Personal, Advisory Board, Participation in advisory board november 2023: Lilly; Financial Interests, Personal, Advisory Board, Advisory board participation June 2020: Novartis. L. Basterretxea: Financial Interests, Personal, Advisory Board: BMS, Ipsen, Astellas, MSD. G. Bruixola: Financial Interests, Personal, Invited Speaker: MSD, Merck, Bristol Myers Squibb; Non-Financial Interests, Principal Investigator, Clinical trial: Gilead Sciences, Bristol Myers Squibb, Debiopharm, Adlay Nortye, Alentis therapeutics. J. Caballero Daroqui: Financial Interests, Institutional, Invited Speaker: Merck KGaA. R. Mesia Nin: Financial Interests, Personal, Advisory Board: Merck, MSD, Bayer, Seattle Genetics, Nanobiotix, Boehringer Ingelheim, Segean; Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Non-Financial Interests, Principal Investigator, Clinical Trial PI: BMS; Non-Financial Interests, Principal Investigator, Observational trial PI: Merck. All other authors have declared no conflicts of interest.