June 9, 2015

With PV-10: One shot, one kill

The University of Illinois at Chicago's College of Medicine's Department of Surgical Oncology's Ajay Maker Laboratory's PV-10 (rose bengal)-related preclinical colorectal cancer work in 2014/2015 employed a single injection of intralesional PV-10.
"Treatment of subcutaneous tumors with a single injection of intralesional PV-10 led to near complete responses in all animals within days of exposure and significant regression of the injected lesions compared to controls (n=6 per group, p=0.027)." See my blog post Intralesional Injection of Rose Bengal Induces an Anti-tumor Immune Response and Potent Tumor Regressions in a Murine Model of Colon Cancer.
Moffitt Cancer Center's preclinical and clinical multi-indication work from 2011 to date also employed a single injection of Provectus' lead oncology agent:
"Treatment of the subcutaneous lesion with a single injection of IL PV-10 led to regression of the injected lesion as well as the distant B16 melanoma lung metastases." See Moffitt's publication Intralesional Injection of Rose Bengal Induces a Systemic Tumor-Specific Immune Response in Murine Models of Melanoma and Breast Cancer.
Single injections of PV-10 were used in Moffitt's clinical feasibility study at AACR and ASCO 2014, and their combining of PV-10 with immune checkpoint inhibitors at SITC 2014. You may even recall Moffitt's rather sensational August 2013 press release: Single Injection May Revolutionize Melanoma Treatment, Moffitt Study Shows.

These single injections more often than not completely destroy the tumors into which they are injected. At ESMO 2014 (and ASCO 2014) Provectus' presented exploratory analysis work of the company's melanoma Phase 2 trial that showed most lesions required 1-2 injections of PV-10 for complete destruction (i.e., complete response). Provectus' primary and secondary liver cancer Phase 1 and expanded Phase 1 liver trials sees tumors injected once, too. The company's recurrent breast cancer Phase 1 trial of several years ago also saw patients have their lesions injected once.

A single injection of PV-10 matter...so what?

First, few injections or one injection per lesion bodes very well for patient compliance with PV-10.

Second, one injection achieving complete response should mean PV-10 is absolutely and relatively more effective than other approved and investigational agents also trying hard to destroy tumors. More with less might lead to much more with more.

Third, more robust efficacy at the so-called local level of lesion injection that leads to complete response (complete destruction) might mean greater immunological signalling of the immune system and thus a better result for destroying cancer elsewhere in the body.

Big Pharma admits that while they are pretty good at shrinking tumors, they are not good at getting rid of them. See my February 2014 blog post Big Pharma has a Shrinkage Problem.

Oddly, at ASCO 2015 Dr. James Allison, PhD said ignore the tumor and just work on the immune system, while attempting to patent the treatment combination of an oncolytic virus and immune checkpoint inhibition. See the blog's news page's ASCO Day #3, sampling (May 31, 2015).

"Up-and-coming" oncolytic virus company Viralytics' lead investigational drug based on Coxsackievirus A21 requires a multi-day, multi-injection per lesion approach (i.e., 10 series of injections).

Amgen's talimogene laherparepvec, as part of their collaboration with Bristol-Myers to combine T-Vec and ipi, was administered by intratumoral injection on day 1 of week 1, day 1 of week 4, and then every two weeks thereafter.

Amgen's preclinical work of T-Vec presented at AACR 2015 exploring the efficacy of the combination of T-Vec and immune checkpoint blockade required multiple injections of the intralesional/intratumoral agent.

Idera's recent "strategic clinical research alliance" with MD Anderson Cancer Center to combine the company's intratumoral toll receptor with ipilimumab in patients with advanced melanoma is the logical combination of a co-stim agent (Idera's IMO-2125) with a co-inhibitory agent (CTLA-4 ipi). Interestingly, or perhaps not so interestingly, IMO-2125 requires injections over multiple days (i.e., 4-5) and achieves less efficacy than PV-10.

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