LBA46 - SAKK 11/16, a phase IIa trial evaluating overall survival (OS) for recurrent/metastatic Head & neck squamous cell carcinoma (RMHNSCC) patients (pts) progressing after ≥ 1 line of systemic therapy, treated with MVX-ONCO-1, a novel, first in class cell encapsulation-based immunotherapy

Background

MVX-ONCO-1 is a personalized, subcutaneous (sc) cancer vaccine combining irradiated autologous tumor cells and devices containing allogeneic cells producing the potent adjuvant GM-CSF. Positive clinical data in RMHNSCC pts with evidence of immune education in a Phase I study triggered this multicenter phase IIa trial.

Methods

16 pts with RMHNSCC, progressing after ≥1 line of systemic therapy, with measurable disease and ECOG PS 0-2 were enrolled. Pts received 6 sc treatments over 8 weeks (wks). Primary endpoint was OS at 26 wks. An unplanned interim review of the first 10 pts revealed 7 had met the 26 wks OS endpoint. Using the conditional power method of Kieser et al. sample size was reduced from 39 to 21 pts keeping the same one-sided type 1 error rate of 5% and power of 80%. The null hypothesis in the adaptive design can be rejected if among the 21 pts there are ≥11 survivors at 26 wks. Response and safety were secondary endpoints.

Results

Enrollment was closed early as primary endpoint was met ahead of schedule. Median OS is 11.4 months (mo) and OS at 12 and 18 mo are 49.2% and 31.6% respectively. Partial Response (PR) and Complete Response (CR) were observed, including CR ongoing for >17 mo in a nivolumab refractory pt. Several pts are alive with no active metastatic disease, including long-term survivors (> 3 years). ORR at 26 wks is 12.5% while DCR at 6 wks is 75% of pts. No systemic adverse events related to therapy was reported. Strong correlation between OS and Delayed Type Hypersensitivity (DTH) was observed. At 12 mo, 100% of DTH+ pts are alive compared to only one DTH- pt.

Conclusions

MVX-ONCO-1 is a novel personalized cancer vaccine with very good safety profile. Clinically meaningful prolonged survival, PR and CR were observed in IO refractory RMHNSCC pts. Prolonged OS correlates strongly with immune education, DTH being a potential biomarker to be validated in future studies. MVX-ONCO-1 is the first cancer vaccine associated with prolonged survival in advanced chemo / IO refractory disease in monotherapy without maintenance.

Clinical trial identification

NCT02999646.

Editorial acknowledgement

Legal entity responsible for the study

MaxiVAX.

Funding

MaxiVAX, Rising Tide Foundation For Clinical Cancer Research, Gateway for Cancer Research, Swiss Cancer League, Horizon 2020 Research & Innovation EU, Coromandel, The Philantropy Settlement.

Disclosure

N. Mach: Financial Interests, Personal, Stocks/Shares, Co-Founder: MaxiVAX. E. Charrier: Financial Interests, Personal, Full or part-time Employment: Maxivax. J.N. Grogg: Financial Interests, Personal, Full or part-time Employment: MaxiVAX SA. J. Renaux: Financial Interests, Personal, Full or part-time Employment, Employed as Director of Clinical Operations at MaxiVAX SA.: MaxiVAX SA; Financial Interests, Personal, Stocks/Shares: GSK. M. Joerger: Financial Interests, Institutional, Coordinating PI, Clinical study activity: Basilea, Bayer, BMS, Immunophotonics, MSD, Novartis, Roche; Financial Interests, Institutional, Other, Clinical study activity: DaiichySankyo; Financial Interests, Institutional, Local PI, Clinical study activity: Innomedica; Non-Financial Interests, Advisory Role: Novartis, AstraZeneca, Basilea, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi. O.A. Michielin: Financial Interests, Institutional, Invited Speaker: BMS, Amgen, Pierre Fabre, Roche; Financial Interests, Institutional, Writing Engagement: BMS; Financial Interests, Institutional, Advisory Board: BMS, Amgen, Roche, Novartis, Pierre Fabre, MSD; Financial Interests, Personal, Other, Advisory Role: BMS, MSD, Roche, Novartis, Pierre Fabre, Amgen, GSL; Financial Interests, Personal, Member of Board of Directors, Co-Founder and member of the Scientific Board: Cellula Therapeutics; Financial Interests, Institutional, Research Grant: BMS, MSD, Pierre Fabre, Amgen, Merck; Financial Interests, Institutional, Funding: BMS, MSD, Pierre Fabre, Amgen, MSD; Non-Financial Interests, Principal Investigator: BMS, MSD, Amgen, Roche, Pierre Fabre, Novartis. All other authors have declared no conflicts of interest.