Abstract 681P
Background
While check point inhibitors (CPI) targeting PD-1 are a standard of care in recurrent or metastatic SCCHN (R/M-SCCHN), the role of anti-CTLA-4 remains uncertain. We evaluated whether escalated therapy targeting PD-1 and CTLA-4 is superior to docetaxel (DOC) in nivolumab-refractory patients (pts).
Methods
This open-label randomized phase II trial compared efficacy and safety of nivolumab + ipilimumab (NIVO/IPI) to docetaxel in RM-SCCHN or carcinoma of nasal sinus. Adult pts with measurable disease after platinum and early progression on NIVO (≤6 months) were randomized. Availability of tumor tissue was mandatory for 1:1 randomization between NIVO 3mg/kg Q2W + IPI 1mg/kg Q6W or DOC 75 mg/m2 Q3W. Primary endpoint: objective response rate (ORR). Sample size was N= 154 (1-sided a= 0.05, P80%). FPI was JUL 2018. Early termination occurred in FEB 2020 due to change of treatment landscape. Descriptive analyses were therefore applied and included progression-free survival (PFS), overall survival (OS) and safety (adverse events (AE) according to CTCAE V4.03).
Results
N=32 pts were randomized: NIVO/IPI, n =14; DOC, n = 17. Median age was 64 yrs. 71.0% were male. 96.8 % had RM-SCCHN. NIVO/IPI vs. DOC achieved an ORR of 0% (0 of 14; 95%CI 0-23.2) and 17.6% (3 of 17; 95%CI 3.8-43.4), respectively. Median and 6-months PFS rate was 1.97 mo. (95%CI, 1.25-2.36), 7.1% vs. 3.66 mo. (95%CI, 1.25-2.3), 25% and median and 1 year OS rates were 3.97 mo. (95%CI, 1.64-18.6), 28.6% vs. 11.9 mo. (95%CI, 1.84-21.0), 44.6% for NIVO/IPI and DOC, respectively. Treatment related (TR)AE were recorded in 38.5% vs. 68.8% and led to discontinuation in 7.7% vs. 18.8% for NIVO/IPI or DOC, respectively. Table: 681P
Key results of OPTIM
| Tumor localization | NIVO/IPI, n=14 | Docetaxel, n=17 | Total, n=32 |
| Oral cavity | 6, 42.9% | 1, 5.9% | 7, 22.6% |
| Oropharynx (OPC) | 5, 35.7% | 7, 41.2% | 12, 38.7% |
| Hypopharynx | 2, 14.3% | 4, 23.5% | 6, 19.4% |
| other | 1, 7.1% | 5, 29.4% | 6, 18.8% |
| P16+ OPC | 1/5, 20.0% | 1/6, 16.7% | 2/11, 18.2% |
| PD-L1: TPS ≥1% | 8, 57.1% | 8, 47.1% | 16, 51.6% |
| Smoking status | |||
| Current or former | 11, 78.6% | 14, 82.3% | 25, 80.6% |
| ORR (n, %) | |||
| CR | 0, 0% | 0, 0% | |
| PR | 0, 0% | 3, 17.6% | |
| SD | 3, 21.4% | 5, 29.4% | |
| PD | 8, 57.1% | 3, 17.6% | |
| NE | 3, 21.4% | 6, 35.3% | |
| PFS, mo (95%CI) | 1.97 (1.25-2.36) | 3.66 (1.25-2.36) | |
| OS, mo. (95%CI) | 3.97 (1.64-18.6) | 11.9 (1.84-21.0) | |
| TRAE (90%CI) | 38.5% (16.6-64.5) | 68.8% (17.8-60.9) | |
| Grade ≥3 TRAE (90%CI) | 15.4% (1.8-41.0) | 37.5% (17.8-60.9) | |
| Discontinuation due to AE | 7.7% | 18.8% |
Conclusions
OPTIM is the first randomized trial to assess NIVO/IPI post IO. NIVO-refractory pts did not respond to salvage NIVO/IPI. Instead, data support the use of DOC after failure of platinum and nivolumab treatments. A major limitation is the early termination of our trial.
Clinical trial identification
NCT03620123.
Editorial acknowledgement
Legal entity responsible for the study
Working Group Medical Oncology (AIO) Clinical Trials GmbH.
Funding
BMS.
Disclosure
V. Gruenwald: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eisai, Ipsen, Janssen-Cilag, Merck Serono, MSD, Pfizer, Roche, Novartis, Astellas; Financial Interests, Personal, Advisory Board: BMS, Eisai, Merck Serono, MSD, Nanobiotix, Pfizer, Roche, Apogepha, EUSA Pharm, Debiopharm, Oncorena, PCI Biotech; Financial Interests, Personal, Stocks/Shares: BMS, MSD, AstraZeneca, Seattle Genetics; Financial Interests, Invited Speaker: BMS, PharmaMar; Financial Interests, Personal and Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: MSD, BMS; Financial Interests, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Eisai, Novartis; Financial Interests, Institutional, Invited Speaker: Ipsen; Non-Financial Interests, Member: ASCO, German medical Oncology and Hematology Society; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Leadership Role: Working Group Medical Oncology. M. Tometten: Financial Interests, Personal, Advisory Board: Hexal, Merck, Incyte. P. Ivanyi: Financial Interests, Personal, Invited Speaker: Apogepha, BMS, Bayer, Boehringer Ingelheim, ClinSol, DKG-Onkoweb, Dicephera, Eisai, H5Oncology, Ipsen, Merck, MSD, Onkowissen, Pfizer, Roche, GSK, PharmaMar, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, Bayer, Dicephera, Eisai, Ipsen, Merck, MSD, Onkowissen, Pfizer; Financial Interests, Personal, Expert Testimony: ClinSol, EMD Serono, Merck, Metaplan, Pfizer; Financial Interests, Personal, Stocks/Shares: BB-Biotech; Financial Interests, Institutional, Invited Speaker: BMS, AstraZeneca, GSK, Ipsen, MSD; Non-Financial Interests, Other, Spokesman: Interdisciplinary Kindey Cancer Group of German Cancer Society. M. Mänz: Other, Personal, Full or part-time Employment: Corbin Research. W. Weichert: Financial Interests, Personal, Advisory Board, Speakers Bureau and Advisory Boards: Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, Amgen, Astellas, Eisai, Johnson&Johnson, Janssen, Illumina, Siemens, Agilent, ADC, GSK and Molecular Health; Financial Interests, Institutional, Research Grant: Roche, MSD, BMS, AstraZeneca. D.A. Hahn: Financial Interests, Personal, Advisory Board, advisory board head and neck cancer, publication of case report nivolumab in head and neck cancer patients: BMS, Merck; Financial Interests, Personal, Advisory Board, advisory board head and neck cancer, invited speaker: MSD; Financial Interests, Personal, Advisory Board, advisory board Hodgkin lymphoma, invited speaker: Takeda. All other authors have declared no conflicts of interest.