653O - Neoadjuvant nivolumab (N) before chemoradiation (CRT) in high-risk HPV driven oropharynx cancer (OPC) - IMMUNEBOOST-HPV: A multicenter randomized phase II trial

Background

Some patients (pts) with HPV-driven OPC have a less favorable prognosis. We aimed to evaluate the feasibility of N prior to CRT in this population.

Methods

HPV driven OPC pts (p16+ & HPV-DNA+) with advanced disease (T4, N2/N3) or a smoking history >10 p/y were randomly allocated 1:2 to receive cisplatin (Cis)-based CRT or 2 cycles of N 240 mg followed by same CRT. Primary Endpoint is the rate of pts who receive Full Treatment in Due Time (FTDT) defined as: a) 2 N cycles (day 1, day 14-16) b) CRT started between days 28-37 after the 1^st N cycle c) No RT break ≥1 week d) RT dose >95% of theoretical dose e) Cis dose ≥200 mg/m² In the Experimental Arm (EA), the trial was designed with FTDT rate of 88% considered as inacceptable versus an alternative of 98%, type I error of 0.10, and type 2 error of 0.08. HPV16 circulating DNA was quantitatively monitored at baseline and after CRT.

Results

From 07/2019 to 09/2021, 61 pts were randomized: 41 in the EA, 20 in the Control Arm (CA). Median age was 60 years, 77% men, 72% current or former smokers, 57% stage III disease (TNM8). In the EA, 4 pts received < 200mg/m² Cis (2 kidney failures, 2 ototoxicity) and 1 pt had RT-delay (day 38, logistical issues). All pts received the planned RT dose. One pt in the CA had a 9-day RT break (hemorrhage). In total, 36 pts (88%, 95% confidence interval (CI) [74; 96]) of the EA met FTDT criteria, which is < the lower limit of 39 pts set by the protocol. In the CA, 19 pts (95%, 95%CI [75; 99.9]) met FTDT criteria. 14 N-related Adverse Events (AE) occurred in 8 pts including 5 serious AE (ankylosing spondylitis flare-up, hepatic cytolysis, 2 colitis, diabetic ketoacidosis). Two pts in the EA had a partial response after N. Three months after CRT, rates of complete and partial responses were 53% and 45% in the EA and 65% and 35% in the CA. One pt of the EA had a doubtful new lesion (node), not confirmed later. At baseline, HPV16ctDNA was positive in 34 of 47 tested pts. Among them, DNA ranged from 33 to 38275 cp/mL and 21 pts were tested after CRT and all had complete clearance.

Conclusions

N prior to CRT did not reach the expected feasibility aim, due to decreased Cis dose (renal/ototoxicity), potentially related to N. Progression-free and overall survival will be evaluated in both arms.

Clinical trial identification

NCT03838263.

Editorial acknowledgement

Legal entity responsible for the study

Unicancer.

Funding

Partial funding from BMS - study CA209-970.

Disclosure

H. Mirghani: Financial Interests, Institutional, Advisory Role: MSD; Financial Interests, Institutional, Other, Travel, acommodation exepenses: BMS. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics; Financial Interests, Institutional, Invited Speaker: BMS, AstraZeneca, ISA pharmaceutics, MSD, DebioPharma, Ayala, Novartis. H. Pere: Financial Interests, Institutional, Invited Speaker: MSD, Janssen; Financial Interests, Institutional, Advisory Role: Seegen. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Innate Pharma, Merck Serono, Roche; Financial Interests, Institutional, Other, research funding: Seagen; Non-Financial Interests, Principal Investigator: AstraZeneca. L. Geoffrois: Financial Interests, Personal, Advisory Board, Ad Board RCC: Ipsen; Financial Interests, Personal, Invited Speaker: Ipsen, BMS, Merck Serono, MSD; Financial Interests, Personal, Advisory Board, Ad Board Bladder Cancer: Merck Serono; Financial Interests, Personal, Advisory Board, Melanoma: Novartis; Financial Interests, Personal, Advisory Board, Head and Neck/RCC: MSD; Financial Interests, Personal, Advisory Board, Bladder cancer: Pfizer; Financial Interests, Institutional, Invited Speaker: MSD, BMS, Roche; Financial Interests, Institutional, Research Grant: Novartis. F. Clatot: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Role: Merck Serono, MSD, BMS, Roche, Lilly, AstraZeneca. Y. Tao: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, travel: MSD, Merck Serono. C. Badoual: Financial Interests, Personal, Invited Speaker: Merck. A. Auperin: Financial Interests, Personal, Funding: F. Hoffmann-La Roche. All other authors have declared no conflicts of interest.