Clinical Trials

Date: 2018-11-02

Type of information: Treatment of the first patient

phase: 1-2

Announcement: treatment of the first patient

Company: Bavarian Nordic (Denmark)

Product: CV-301 in combination with durvalumab

Action mechanism:

  • Durvalumab (Imfinzi®) is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Durvalumab blocks these signals, countering the tumour’s immune-evading tactics. This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells.
  • AstraZeneca recently received accelerated approval from the US FDA for Imfinzi® in previously treated patients with advanced bladder cancer. Imfinzi is currently approved in the US and Canada for the treatment of patients with unresectable Stage III NSCLC who had not progressed following platinum-based chemoradiation therapy and under regulatory review in the EU, Japan and other jurisdictions with expected decisions in the second half of 2018.
  • CV301 is an immunotherapy product candidate for the treatment of multiple cancers. It originates from the same poxvirus technology platform as Prostvac®.
  • Both products are prime-boost vaccines sequentially combining two different poxviruses (vaccinia and fowlpox). While Prostvac® incorporates a single antigen over-expressed in prostate cancer (PSA), CV-301 incorporates two antigens (CEA and MUC-1) that are over-expressed in other major cancers, including breast, colon, bladder and other cancers, which makes CV-301 potentially applicable in various cancers. CV301 incorporates a modified version of vaccinia (MVA-BN, a proprietary technology of Bavarian Nordic) as a priming dose, followed by multiple fowlpox boosts, and encodes the TRICOM costimulatory molecules.
  • Preclinical data has shown that vaccination resulted in the induction of tumor specific T-cells that infiltrated the tumor resulting in the upregulation of PD-L1 on 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.

Disease: metastatic colorectal cancer, metastatic pancreatic cancer

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

  • This is a dual arm, open label phase I/II study to evaluate the safety and clinical activity of the combination of durvalumab with CV301 in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic cancer whose disease is stable on, or responding to 1st line therapy for metastatic disease. Patients with metastatic colorectal or pancreatic adenocarcinoma who still have an adequate performance status and normal hepatic and renal function will be eligible. (NCT03376659)

Latest news:

  • • On November 2, 2018, Bavarian Nordic announced that the first patient has been dosed in a clinical study evaluating CV301, the Company’s targeted immunotherapy candidate, and durvalumab, AstraZeneca’s PD-L1 inhibitor, in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic cancers.
  • The investigator-sponsored trial is being led by Dr. Michael Pishvaian, Associate Professor in the Department of Hematology/Oncology at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, D.C., with material support from Bavarian Nordic and AstraZeneca. The clinical trial is being conducted at several other top cancer centers including the Mayo Clinic, Indiana University and Emory University. The trial will begin with a small lead-in study to determine the safety and tolerability of the combination, as well as the recommended Phase 2 dose of durvalumab in combination with CV301 and maintenance chemotherapy.
  • The Phase 2 portion of the study will consist of two parallel trials, enrolling up to 26 patients with metastatic disease for each disease setting. The primary endpoint for both arms of the study will be progression-free survival (PFS) with multiple secondary endpoints, including objective response rate (ORR), overall survival (OS), and disease control rate (DCR).

Is general: Yes