1120P - Subgroup efficacy in patients receiving intralesional rose bengal to all existing melanoma in phase II study PV-10-MM-02

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Melanoma and other Skin Tumours
Presenter Sanjiv Agarwala
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors S.S. Agarwala1, J.F. Thompson2, B.M. Smithers3, M. Ross4, C.R. Scoggins5, B.J. Coventry6, S.J. Neuhaus6, D.R. Minor7, J.M. Singer8, E. Wachter8
  • 1St Lukes Cancer Center, St Lukes Hospital and Health Network, 18034 - Center Valley/US
  • 2Surgery, Melanoma Institute Australia, Sydney/AU
  • 3Queensland Melanoma Project, Princess Alexandra Hospital, Wooloongabba/AU
  • 4Surgical Melanoma, MD Anderson Cancer Center, Houston/US
  • 5Surgery, University of Louisville, Louisville/US
  • 6Surgery, Royal Adelaide Hospital, Adelaide/AU
  • 7Medical Oncology, California Pacific Medical Center, San Francisco/US
  • 8Clinical Development, Provectus Biopharmaceuticals, Knoxville/US

Abstract

Aim

The safety and efficacy of intralesional (IL) treatment of refractory cutaneous melanoma with rose bengal disodium (PV-10) was evaluated in an 80 patient (pt) international, multicenter, single arm phase II trial (NCT00521053).

Methods

Patients refractory to a median of 6 previous interventions with 6.3 cm median sum lesion diameter in biopsy-confirmed melanoma received PV-10 into up to 20 cutaneous and subcutaneous lesions up to 4 times over a 16-week period and were followed for 52 weeks. Best overall response rate (BORR) was assessed in up to 10 injected target lesions. Secondary endpoints included assessment of duration of response, BORR of untreated bystander lesions, overall survival and adverse events. Confidence intervals for response were based on the exact cumulative probabilities of the binomial distribution (95% confidence intervals).

Results

Overall, PV-10 was well tolerated and 41 of 80 ITT pts met the primary endpoint of objective response (CR + PR) in their injected target lesions (51% ORR CI 40-63%, 26% CR). In the subgroup of 28 pts who received PV-10 into all existing melanoma lesions, ORR was 71% (CI 51-87%) with 50% CR (CI 31-69%). In these pts plus 26 pts with uninjected disease limited to bystanders (i.e., 54 pts) CR was achieved in 232 of 363 injected lesions (64% CR): 121 lesions required a single injection for CR, 84 required 2 injections, 22 required 3 injections and 5 required 4 injections. Additionally, 10 of 28 uninjected bystander lesions achieved CR.

Conclusions

Recurrent locoregional melanoma can be a source of persistent morbidity, including disfigurement frequently accompanied with pain, ulceration, bleeding and infection. The high rate of symptom control in refractory patients, manifest in CR of injected lesions after minimal intervention, was the basis for a breakthrough therapy designation application to the US FDA based on the 28 patient “all treated” subgroup, and implications of the Agency's ruling on this application will be presented. Although the primary ablative effect is responsible for CR in injected tumors, durability of response and bystander response implicate an immunologic mechanism of action secondary to ablation.

Disclosure

J.M. Singer: Employee, stock ownership; E. Wachter: Employee, stock ownership. All other authors have declared no conflicts of interest.