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Other cancers

CV301 - immunotherapy candidate for multiple cancers

PHASE 2


CV301 is an active immunotherapy candidate that targets two tumor-associated antigens, CEA and MUC-1, long known to be overexpressed in most solid tumors. Preclinical data shows that antigen specific vaccination results in T cell infiltration into areas of antigen expression and upregulation of PD-L1 on antigen expressing tumor cells. The upregulation of PD-L1 is a marker indicating the tumor is under attack from T-cells, presenting an opportunity for a greater response in patients who might otherwise not benefit from treatment with a checkpoint inhibitor alone.

CV301 is in the unique position to potentially demonstrate a broad proof of concept not only in settings where checkpoints have set a new standard of survival, but also in cancers, such as micro-satellite stable colorectal, where checkpoint inhibitors have yet to demonstrate single-agent activity and may require combinations with other agents. The CV301 strategy has been adapted during 2018 focusing our resources on smaller studies, some with adaptive designs, where there remain options to demonstrate rapid proof of concept of the combination with checkpoint inhibition.

Ongoing or planned trials

Phase 2, Multicenter, Single-Arm Trial of CV301 in Combination With PD-1/L1 Blockade in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Location: USA
Read more: NCT03628716
Phase 2 Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Resectable Hepatic-Limited Metastatic Colorectal Cancer
Location: USA
Read more: NCT03547999
A Phase 1/2 Trial of the PD-L1 Inhibitor, Durvalumab Plus CV301 in Combination With Maintenance Chemotherapy for Patients With Metastatic Colorectal or Pancreatic Adenocarcinoma
Location: USA
Read more: NCT03376659

Gatti-Mays ME, Strauss J, Donahue RN, et al.
A Phase 1 Dose Escalation Trial of BN-CV301, a Recombinant Poxviral Vaccine Targeting MUC1 and CEA with Costimulatory Molecules

Clin Cancer Res May 20 2019

Schlom J, Gulley JL
Vaccines as an Integral Component of Cancer Immunotherapy

JAMA. 2018;320(21):2195-2196. doi:10.1001/jama.2018.9511

Foy SP, Mandl SJ, dela Cruz T, Cote JJ, et al.
Poxvirus-based active immunotherapy synergizes with CTLA-4 blockade to increase survival in a murine tumor model by improving the magnitude and quality of cytotoxic T cells

Cancer Immunol Immunother. 2016; 65: 537–549.

Foy SP, Sennino B, dela Cruz T. et al.
Poxvirus-Based Active Immunotherapy with PD-1 and LAG-3 Dual Immune Checkpoint Inhibition Overcomes Compensatory Immune Regulation, Yielding Complete Tumor Regression in Mice

PLoS One. 2016 Feb 24;11(2):e0150084.

Foy SP, Mandl SJ, dela Cruz T, et al.
Magnitude and quality of tumor-infiltrating T cell response upon poxvirus-based active immunotherapy alone and in combination with CTLA-4 immune checkpoint inhibition.

J Clin Oncol. 2014;32:5s suppl: Abstract 3013.

Foy SP, Rountree RB, Joseph Cote J, et al.
Anti-tumor efficacy of poxvirus-based active immunotherapy alone and in combination with reduced doses of multiple immune checkpoint inhibitors.

J Clin Oncol. 2014;32:5s suppl: Abstract 3058.

Mohebtash M, Tsang KY, Madan RA, et al.
A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer.

Clin Cancer Res. 2011;17:7164-7173.

Gulley JL, Arlen PM, Tsang KY, et al.
Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma.

Clin Cancer Res. 2008;14:3060-3069.

Madan RA, Arlen PM, Gulley JL
PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma.

Expert Opin Biol Ther. 2007;7:543-554.

Arlen PM, Pazdur RM, Skarupa L, et al.
A randomized phase II study of docetaxel alone or in combination with PANVAC-V (vaccinia) and PANVAC-F (fowlpox) in patients with metastatic breast cancer.

Clin Breast Cancer. 2006;7:176-179.