PO.CT01.05 · 临床试验

Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)

海报缩略图：Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)

编号 CT162 展板 26 时间 4/20 02:00–05:00 区域 Section 52 主讲 Manuel Hidalgo, MD;PhD

分会场 Phase II and Phase III Clinical Trials

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作者与单位

Rocio Garcia-Carbonero¹, Roberto Pazo², Teresa Macarulla³, Berta Laquente⁴, Alana Nguyen⁵, Carmen Guillén-Ponce⁶, Andres J. Muñoz⁷, Edward J. Kim⁸, Mireya Cazorla⁹, Tara Seery¹⁰, Miriam Lobo de Mena¹¹, Chris Nevala-Plagemann¹², Vivek R. Sharma¹³, Eva Martinez de Castro¹⁴, Charles Le¹⁵, Ana Mato-Berciano¹⁶, Luis A. Rojas¹⁶, Carmen Blasco¹⁶, Manel Cascallo¹⁶, Manuel Hidalgo¹⁷

¹Hospital Universitario Doce de Octubre, Imas 12, Madrid, Spain,²Hospital Universitario Miguel Servet, Zaragoza, Spain,³Hospital Universitari Vall d’Hebron, Barcelona, Spain,⁴Catalan Institute of Oncologia, Barcelona, Spain,⁵Weill Cornell Medicine/NYP Hospital, New York, NY,⁶Hospital Universitario Ramón y Cajal, Madrid, Spain,⁷Hospital Universitario Gregorio Marañón, Madrid, Spain,⁸UC Davis Comprehensive Cancer Center, Sacramento, CA,⁹Hospital Regional Universitario, Malaga, Spain,¹⁰Hoag Memorial Hospital Presbyterian, Newport Beach, CA,¹¹Consorcio Hospital General Universitario de Valencia, Valencia, Spain,¹²Huntsman Cancer Institute, University of Utah, Salt Lake City, UT,¹³University of Louisville, Louisville, KY,¹⁴Hospital Universitario Marqués de Valdecilla, Santander, Spain,¹⁵Theriva Biologics Inc, Rockville, MD,¹⁶Theriva Biologics SL, Parets del Valles, Spain,¹⁷NYU Langone Health Perlmutter Cancer Ctr., New York, NY

摘要 Abstract

Background: VCN-01 (zabilugene almadenorepvec) is an oncolytic adenovirus expressing hyaluronidase to degrade tumor stroma, facilitate chemotherapy penetration and stimulate tumor immunity, which is being developed for different cancer indications. The randomized, open-label, Phase 2b VIRAGE trial tested the efficacy and safety of 2 intravenous (IV) doses of VCN-01 combined with standard of care (SoC) gemcitabine/nab-paclitaxel (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 (1x10 13 vp/dose) 1 week prior to cycles 1 and 4 of GA (Arm II). Primary endpoints were overall survival (OS) and safety. Secondary objectives included progression free survival (PFS), objective response rates (ORR), duration of response (DoR) and Ca19.9 changes. VCN-01 genomes in blood and serum levels of neutralizing anti-adenovirus antibodies (anti-Ad-NAb's) were also analyzed. Results: 96 patients in the trial received at least 1 dose of GA or VCN-01+GA (48 patients in each arm). Median OS was 10.8 vs. 8.6 months for Arm II and Arm I, respectively (HR 0.57, 95% CI 0.34-0.96; P =0.055) and PFS was 7.0 vs. 4.6 months (HR 0.55, 95% CI 0.34-0.88; P =0.011). OS benefits with VCN-01+GA vs. GA alone were consistent across different subgroups, including patients aged over 70 years, presence of hepatic metastases, or patients with >2 metastatic sites. Compared to patients in Arm I who started cycle 4 of GA, patients in Arm II who received 2 VCN-01 doses and started cycle 4 of GA 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). ORR was 39.6% vs. 31.3% ( P =0.314), and more patients had target tumor shrinkage with VCN-01 + GA than GA (84.1% vs. 69.8%; P =0.13). DoR was longer for VCN-01+GA (11.2 vs 5.4 months; HR 0.22; 95% CI 0.08 - 0.62; P =0.004) and 8 of 19 patients in this group achieved late objective responses after the second VCN-01 dose (>4 months after randomization). Ca19.9 levels declined more markedly in Arm II, with a median reduction of -61.0% versus -64.9% in Arm I vs. Arm II by cycle 3, and a further decrease to -16.7% vs -86.3% by cycle 9, following the second VCN-01 dose. No correlation between baseline levels of anti-Ad-NAbs and OS or PFS were observed. The peak of viral genome levels in blood was similar between the first and the second dose of VCN-01. Conclusions: Compared to patients in Arm I (GA), mPDAC patients in Arm II (VCN-01+GA) showed improved OS and PFS and later and more durable responses. Patients that received a second VCN-01 dose+GA showed a further delayed disease progression and extended patient survival compared to patients that received equivalent cycles of GA.

利益披露 Disclosure

R. Garcia-Carbonero, Astellas Other, Advisory Board. Ipsen Other, Advisory Board. MSD ). Pfizer ). R. Pazo, Astellas ), Other, Invited Speaker, Advisory Board. Astra Zeneca Other, Expert Testimony, Advisory Board. BMS Other, Invited Speaker, Advisory Board. Eisai Other, Invited Speaker. Ipsen ), Other, Advisory Board. Lilly Other, Expert Testimony. Roche Other, Invited Speaker, Advisory Board. Servier Other, Invited Speaker, Advisory Board. T. Macarulla, Amgen Other, Consultant or Advisory Role. Servier Other, Consultant or Advisory Role, Invited Speaker. Incyte ), Other, Consultant or Advisory Role, Invited Speaker. Sanofi Other, Consultant or Advisory Role. Astra Zeneca ), Other, Consultant or Advisory Role, Invited Speaker. Taiho Other, Consultant or Advisory Role. Celgene ), Other, Consultant or Advisory Role. Eisai Other, Consultant or Advisory Role, Invited Speaker. BeiGene ). Roche Other, Invited Speaker. B. Laquente, Jazz Pharmaceuticals Other, Advisory Board. Astellas ), Other, Advisory Board. Taiho ). Astra Zeneca ). Theriva Biologics ). A. Nguyen, ReMission ). C. Guillén-Ponce, BeOne ). Incyte ). PH Research ). Novartis ). Erytech Pharma ). Halozyme ). Theriva Biologics ). A. J. Muñoz, Leo Pharma ), Other, Advisory Services. Sanofi ), Other, Advisory Services. BMS ), Other, Advisory Services. Celgene ), Other, Advisory Services. GSK Other, Advisory Services. Pfizer Other, Advisory Services. Astra Zeneca Other, Advisory Services. MSD Other, Advisory Services. Lilly Other, Advisory Services. Servier Other, Advisory Services. Roche Other, Advisory Services. Taiho Other, Advisory Services. Regeneron Other, Advisory Services. Rovi Other, Advisory Services. Menarini Other, Advisory Services. Stada Other, Advisory Services. Medscape Other, Advisory Services. E. J. Kim, Relay Therapeutics Other, Advisory Role. Eisai Other, Speakers' Bureau. Pfizer Other, Speakers' Bureau. Merck ). EpicentRx ). Astellas ). Erytech ). Fibrogen ). NGM BIOPHARMACEUTICALS ). Eureka Therapeutics ). Genentech ). GlaxoSmithKline ). M. Cazorla, None. T. Seery, Astellas Other, Advisory Board. Revolution Medicines Other, Advisory Board. M. Lobo de Mena, Astra Zeneca Other, Invited speaker. Incyte Other, Invited speaker. Leo Pharma Other, Invited speaker. Novartis Other, Invited speaker. Servier Other, Invited speaker. C. Nevala-Plagemann, Seagene Other, Advisory Role. V. R. Sharma, Sanofi Other, Invited Speaker. Alexion Other, Invited Speaker. Astra Zeneca Other, Invited Speaker. E. Martinez de Castro, None. C. Le, Theriva Biologics Employment, Stock Option. A. Mato-Berciano, Theriva Biologics Employment, Stock, Stock Option. L. A. Rojas, Theriva Biologics Employment, Stock Option. C. Blasco, Theriva Biologics Employment, Stock, Stock Option. M. Cascallo, Theriva Biologics Employment, Stock, Stock Option, Patent. M. Hidalgo, Champions Oncology Stock, Other, Advisory Board. InxMed Stock, Other, Advisory Board. Oncomatrix Other Business Ownership, Other, Advisory Board. Peaches Other, Advisory Board. Thetis Other, Advisory Board. Velavigo Stock, Other, Advisory Board. BMS g., Board of Directors, non-salaried role), Stock. Guardant Health g., Board of Directors, non-salaried role), Stock. Nelum Pharmaceuticals Other Business Ownership. Incyte ). Theriva Biologics ).

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