Oncolytic Virus Proves Promising in Advanced Melanoma

Despite the various treatment advances in melanoma, advanced stages of the disease remain a significant challenge for oncologists. Novel methods of attacking disease vulnerabilities continue to be developed-one such technique is the use of oncolytic viruses to destroy cancer cells. A couple of studies presented an update on preclinical and clinical progress with CAVATAK, formulated using the common cold Coxsackievirus Type A21 (CVA21), during the Society for Melanoma Research, 2014 International Congress in Zurich, Switzerland, November 13—16.

Despite the various treatment advances in melanoma, advanced stages of the disease remain a significant challenge for oncologists. Novel methods of attacking disease vulnerabilities continue to be developed—one such technique is the use of oncolytic viruses to destroy cancer cells. A company in Australia, Viralytics, has formulated a treatment using the common cold Coxsackievirus Type A21 (CVA21). CAVATAK binds to specific receptor proteins that are highly expressed on a range of cancer cell types, and acts to destroy local as well as metastatic tumor cells through cell lysis and the potential generation of a specific immune response against the cancer cells.

A couple of studies presented an update on preclinical and clinical progress with CAVATAK during the Society for Melanoma Research, 2014 International Congress in Zurich, Switzerland, November 13—16.

A preclinical study evaluated CAVATAK in combination with an anti-mouse PD-1 inhibitory antibody in a B16-ICAM-1 melanoma model.1 CAVATAK was administered intratumorally, while the anti mPD-1 monoclonal antibody (mAb) was delivered via the intraperitoneal route. Following treatment of the primary cutaneous B16-ICAM-1 tumor with 8 cycles of CAVATAK injections and 4 cycles of anti-PD-1 mAb, mice were challenged with an additional subcutaneous administration of B16 cells.

While CAVATAK and the anti-PD-1 mAb were quite efficient by themselves, relative to saline controls, combination of CAVATAK and the anti-PD-1 mAb mediated significantly greater antitumor activity and offered greater survival benefit when compared to the use of either agent alone, the authors reported. A significant finding of the study was the delayed tumor development following a B16 cell challenge when the 2 treatments were combined, compared to other single agent treatments. The authors believe that the findings of their preclinical studies warrant further evaluation of this combination regimen in clinical trials.

Another study presented the results of the CALM study, which investigated the efficacy and safety of intratumoral CAVATAK in 57 patients with treated or untreated unresectable stage IIIC-IVM1c melanoma.2 Patients were administered up to 3x108 CAVATAK intratumorally on study days 1, 3, 5, and 8 and then every 3 weeks for a further 6 injections. The primary endpoint was to achieve >9 of 54 evaluable patients with immune-regulated progression-free survival (irPFS) at 6 months. Secondary endpoints for the study included median irPFS, 1-year survival, median time to response, irRECIST 1.1 BORR, and safety.

The primary endpoint of the study was achieved with 21 of 54 (38.9%) evaluable patients displaying irPFS at 6 months. Preliminary analysis of secondary endpoints presented median irPFS of 4.2 months (95% CI 2.8, 8.3), 1-year survival 65.7% (23 of 35 patients), on-going BORR (irRECIST 1.1) 26.3% (15 of 57 patients), with responses seen in both injected and non-injected lesions, and median time to response 2.8 months. A systemic exposure to CAVATAK following intratumoral injection was detected in >85% of patients. The regimen was quite well tolerated by patients, and there were no grade 3 or 4 product-related adverse events.

Based on the results of this trial, the authors concluded that intralesional CAVATAK is a promising novel oncolytic immunotherapeutic agent with limited toxicity and robust responses in both injected and noninjected lesions in patients with advanced melanoma, and they propose further monotherapy and combination therapy studies with this viral agent.

References

  1. Quah M, Au G, Wong Y, Andtbacka R, Shafren D. Combination of a novel oncolytic immunotherapeutic agent, CAVATAK and PD-1 blockade significantly reduces tumor growth and improves survival in an immune competent mouse melanoma model. Presented at Society for Melanoma Research, 2014 International Congress, November 13-16, 2014, Zurich, Switzerland.
  2. Andtbacka RH, Curti B, Kaufman HL, et al. CALM study: a phase II study of a novel oncolytic immunotherapeutic agent, CAVATAK, delivered intratumorally in patients with advanced malignant melanoma. Presented at Society for Melanoma Research, 2014 International Congress, November 13-16, 2014, Zurich, Switzerland.