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Abstract 5555
VIRAGE trial: randomized Phase IIb, open-label, study of Nab-Paclitaxel and Gemcitabine with/without intravenous VCN-01 in Patients with Metastatic Pancreatic Cancer (mPDAC)
Type: Abstract Category: Pancreatic cancer
| Authors: | R. Garcia-Carbonero1, R. Pazo Cid2, T. Macarulla Mercade3, B. Laquente4, A. Nguyen5, C. Guillen Ponce6, A. Munoz Martin7, E. Kim 8, M. Cazorla9, T. Seery10, M. Lobo de Mena11, C. Nevala-plagemann12, V. Sharma13, E. Martinez de Castro14, C. Le15, M. Kaleko16, M.A. Shallcross17, C. Blasco18, M. Cascallo Piqueras19, M. Hidalgo20; 1Medical Oncology Department, Hospital Universitario 12 de Octubre Imas12, UCM, Madrid, Spain, 2Medical Oncology Department, HospItal Universitario Miguel Servet, Zaragoza, Spain, 3Medical Oncology Dept., VHIO - Vall d'Hebron Institute of Oncology, Barcelona, Spain, 4Medical Oncology Department, ICO - Institut Català d'Oncologia l'Hospitalet (Hospital Duran i Reynals), L'Hospitalet De Llobregat, Spain, 5Internal Medicine, Weill Cornell Medicine - Gastrointestinal (GI) Oncology, New York, United States of America, 6Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain, 7Medical Oncology, Hospital General Universitario Gregorio Maranon, Madrid, Spain, 8UC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Sacramento, United States of America, 9Medical Oncology, HUVV - Hospital Universitario Virgen de la Victoria, Malaga, Spain, 10Medical Oncology Department, Hospital Universitario 12 de Octubre Imas12, UCM, Newport Beach, Ca, AL, United States of America, 11Medical Oncology Department, CHGUV - Consorcio Hospital General Universitario de Valencia, Valencia, Spain, 12Oncology, University of Utah Health - Huntsman Cancer Institute, Salt Lake City, United States of America, 13Medicine, University of Louisville, Louisville, United States of America, 14Oncologist, HUMV - Hospital Universitario Marques de Valdecilla, Santander, Spain, 15Departments of Biometrics, Theriva Biologics, Inc., Rockville, United States of America, 16Research and Development Dept., Theriva Biologics, Inc., Rockville, United States of America, 17Clinical Operations, Theriva Biologics, Inc., Rockville, United States of America, 18Clinical Operations, Theriva Biologics SL, Parets Del Valles (Barcelona)Barcelona, Spain, 19Management, Theriva Biologics SL, Parets Del Valles (Barcelona), Spain, 20Hematology Oncology Department, NewYork-Presbyterian Hospital/ Weill Cornell Medical Center, New York, United States of America |
Background
VCN-01 (zabilugene almadenorepvec) is an oncolytic adenovirus expressing hyaluronidase to degrade tumor stroma, facilitate chemotherapy and enhance the antitumor immune response. Building on an acceptable safety profile and encouraging activity when combined with standard of care (SoC) gemcitabine/nab-paclitaxel (GA), we conducted an open-label, controlled, randomized phase IIb trial to evaluate the efficacy and safety of two doses of VCN-01 with GA in mPDAC
Methods
Chemonaïve mPDAC patients were randomized 1:1 to receive SoC doses of GA on days 1, 8 and 15 of repeated 28-day cycles (Arm I) or 2 separate IV doses of VCN-01 (1x1013 vp/dose) 1 week prior to each of cycle 1 & 4 of GA (Arm II). Primary endpoints were overall survival (OS) and safety. The trial was designed with 80% power to detect OS differences with 2-sided alpha 0.1 in mITT or FAS populations. Secondary objectives included PFS, response rates, duration of response (DoR) and biomarker Ca19.9.
Results
112 patients were randomized. Patients in the mITT population received at least 1 dose of GA (Arm I) or VCN-01 (Arm II). Patients in the FAS population received at least 1 dose of GA (Arm I) or VCN-01 followed by at least 1 dose of GA (Arm II).
| mITT | FAS | |||||
| Arm I (48) | Arm II (53) | HR (95% CI) | Arm I (48) | Arm II (48) | HR (95% CI) | |
OS
mo. |
8.6 |
10.6 |
0.69 (0.42-1.12)
P=0.196 |
8.6 |
10.8 |
0.57 (0.34-0.96)
P=0.055 |
PS
mo. |
4.6 |
5.6 |
0.63 (0.4-1.0)
P=0.047 |
4.6 |
7.0 |
0.55 (0.34-0.88)
P=0.011 |
DoR
mo. |
5.4 |
11.2 |
0.22 (0.08-0.62)
P=0.004 |
5.4 |
11.2 |
0.22 (0.08-0.62)
P=0.004 |
| ORR | 31.3% | 35.8% | 31.3% | 39.6% | ||
| mo. months | ||||||
Compared to patients who started GA cycle 4 alone (Arm I), patients who received 2 VCN-01 doses and started GA cycle 4 (Arm II) showed greater improvement in OS (14.8 vs 11.6 months; HR 0.44; 95% CI 0.21 - 0.92; P=0.046) and PFS (11.2 vs 7.4 months; HR 0.48; 95% CI 0.25 - 0.91; P=0.017). VCN-01 administration was well tolerated. All VCN-01-related serious adverse events (n=13) were resolved, the most common being flu-like symptoms (13,2%), transaminase increase (5.7%) and drug-induced liver injury (3.8%). Viral genome analysis confirmed the bioactivity of the second VCN-01 dose.
Conclusions
This study met its primary endpoints. Patients receiving VCN-01 + GA had improved OS, PFS and DoR compared to GA SoC.
Clinical trial identification
NCT05673811
Editorial acknowledgement