937P - Survival outcomes in phase I trial combining VCN-01 and durvalumab (MEDI4736) in subjects with recurrent/metastatic head and neck squamous cell carcinoma refractory to previous immunotherapy treatment

Background

VCN-01 is an oncolytic adenovirus expressing hyaluronidase that increases immune check-point inhibitor uptake in preclinical models suggesting it could reduce resistance to anti-PD(L)-1 therapies. Initial results from phase 1 trial NCT03799744 showed that sequential administration of VCN-01 and Durvalumab is feasible with an acceptable safety profile. Here we present the clinical outcomes data.

Methods

VCN-01 at 3,3E12 and 1E13 viral particles [vp] were administered with a fixed dose of Durvalumab (1500 mg) in a 3+3 design in R/M HNSCC pts previously treated with anti-PD(L)-1 agents. Concomitant (single dose VCN-01 + Durvalumab on day 1, CS), and sequential (single dose of VCN-01 on day -14 + Durvalumab on day 1; SS) schedules were tested. Durvalumab continued q4 weeks until progression in both schedules. Fresh tumor biopsies were taken at baseline, post-VCN-01 and post-Durvalumab.

Results

20 patients were enrolled (median prior lines: 4, range: 1-7), from which 6 in the CS (all 3.3E12 vp) and 12 in the SS (6 at 3,3E12vp and 6 at 1E13 vp) were evaluable for response. Objective response rate (ORR), median PFS and OS (95% CI) in the CS at 3,3E12vp were 0% 1,7 months (1.6-NE) and 10.4 months (8.9-NE), respectively. For SS patients at 3.3E12 vp, ORR, median PFS and OS were 16%, 3.7 months (2.2-NE) and 15.5 months (15.1-NE) respectively. Values for SS patients at 1E13 vp were 0%, 2.1 months (1.4-NE) and 15+ months. 11 patients (61.1%) were alive >12 months (2 in CS; 5 in SS at 3.3E12 vp, 4 in SS at 1E13 vp). Unexpectedly most of them appeared to benefit from subsequent treatment. The 3 patients with the longest survival showed immune-mediated DLT. Increase of PDL1-CPS (16/21; p=0.013) and CD8 T-cells (12/21; p=0.007) from baseline were found in tumor biopsies both post-VCN-01 and post-Durvalumab. A correlation between OS and CPS at D8 was observed (p=0.005). Viral genome analysis and other biologic markers confirmed sustained VCN-01 replication.

Conclusions

Encouraging survival was observed in patients progressing to anti-PD(L)-1 agents after systemic VCN-01 with Durvalumab. VCN-01-induced upregulation of PD-L1, which correlated with enhanced patient survival.

Clinical trial identification

NCT03799744.

Editorial acknowledgement

Legal entity responsible for the study

Institut Català d'Oncologia.

Funding

Funded by THERIVA BIOLOGICS (formerly VCN Biosciences). Durvalumab was provided by AstraZeneca.

Disclosure

M. Jové: Financial Interests, Personal, Invited Speaker, Educational: AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker, Educational activity: BMS; Other, Other, Travel, accomodation and expenses: Takeda, Roche, MSD, VCN. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme (MSD), Rakuten Pharma, Boehringer Ingellheim, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. 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, Other, 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; Financial Interests, Institutional, Funding: GSK; Non-Financial Interests, Institutional, Product Samples: ROCHE. A. Hernando Calvo: Other, Other, Travel support: Merck Serono, Kyowa Kirin. C. Erasun Lecuona: Financial Interests, Personal, Full or part-time Employment: BMS. A. Mato-Berciano: Financial Interests, Personal, Full or part-time Employment: Theriva Biologics. M.V. Maliandi: Financial Interests, Personal, Full or part-time Employment: Theriva Biologics. C. Le: Financial Interests, Full or part-time Employment: Theriva Biologics. P.G. Nuciforo: Financial Interests, Personal, Advisory Board: BAYER, MSD ONCOLOGY; Financial Interests, Personal, Invited Speaker: NOVARTIS; Financial Interests, Personal, Other, Consultant: TARGOS Molecular Pathology. R. Alemany: Financial Interests, Personal, Stocks/Shares: Theriva Biologics; Financial Interests, Institutional, Research Funding, T: Theriva Biologics SL; Financial Interests, Institutional, Speaker, Consultant, Advisor: Theriva Biologics SL. G. Capella: Financial Interests, Personal, Other, Consultancy: THERIVA BIOLOGICS; Financial Interests, Personal, Stocks/Shares: THERIVA BIOLOGICS; Non-Financial Interests, Member of Board of Directors, Chairperson 2022-2024: International Society for the Study of Hereditary Gastrointestinal Cancer; Non-Financial Interests, Member of Board of Directors: FUREGA Fundació Per la Recerca en Gastroenterologia; Non-Financial Interests, Member: ASCO, EACR-ASEICA, EHTG European Hereditary Tumor Group. C. Blasco: Financial Interests, Personal, Full or part-time Employment: Theriva Biologics SL. M. Cascallo Piqueras: Financial Interests, Personal, Full or part-time Employment: Theriva Biologics SL; Financial Interests, Personal, Stocks/Shares: Theriva Biologics. R. Mesia Nin: Financial Interests, Personal, Advisory Board: Merck, MSD, Bayer, Seattle Genetics, Nanobiotix, Boehringer, 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.