Thursday, May 26, 2016

ASCO 2016: New studies! Rose Bengal and Pembro for Stage IV y'all!!! Enrolling! For Stage IIIb/c: PV-10 vs T-VEC.

I've been singing about Rose Bengal for some time!  Recently this study showed a bit about how it works...and there are links to previous posts  Now there is this:

Intralesional rose bengal for treatment of melanoma.  ASCO 2016. #9600.  J Clin Oncol 2016.  Agarwala, Andtbacka, Rice, et al.

Background: Intralesional rose bengal (PV-10) is an investigational small molecule ablative immunotherapy that can elicit primary ablation of injected tumors and secondary T-cell activation. Phase 2 testing in Stage III-IV melanoma yielded a 51% objective response rate (ORR) with 50% complete response (CR) when all disease was injected. PV-10 is currently undergoing phase 3 testing as a single agent in patients with locally advanced cutaneous melanoma and phase 1b testing in combination with immune checkpoint inhibition for more advanced disease. Methods: Study PV-10-MM-31 is an international multicenter, open-label, randomized controlled trial of PV-10 versus investigator’s choice of chemotherapy (dacarbazine or temozolomide) or oncolytic viral therapy (talimogene laherparepvec). A total of 225 subjects with locally advanced cutaneous melanoma (Stage IIIB or Stage IIIC recurrent, satellite or in-transit melanoma) randomized 2:1 will be assessed for progression free survival (PFS) by RECIST 1.1 (using blinded Independent Review Committee assessment of study photography and radiology data). Comprehensive disease assessments, including review of photography and radiology data, are performed at 12 week intervals; clinical assessments of progression status are performed at 28-day intervals. Study PV-10-MM-1201 is an international multicenter, open-label, sequential phase study of PV-10 in combination with pembrolizumab. Stage IV metastatic melanoma patients with at least one injectable cutaneous or subcutaneous lesion who are candidates for pembrolizumab are eligible. In the current phase 1b portion of the study, up to 24 subjects will receive the combination of PV-10 and pembrolizumab (PV-10 + standard of care). In phase 2 an estimated 120 participants will be randomized 1:1 to receive either PV-10 and pembrolizumab or pembrolizumab alone. The primary endpoint for phase 1b is safety and tolerability with PFS a key secondary endpoint; PFS is the primary endpoint for phase 2. Clinical trial information: NCT02288897

Really love that there is a head to head look at PV-10 vs T-VEC.  The fact that they had to throw chemo in there pisses me off...but...  Love the idea of anti-PD1 with intralesionals.  Many researchers have been looking at this as the best way to use intralesional therapy.  

And then there's this:  Rose Bengal and Radiation....Overall response rate of 87%!

A phase 2 study of intralesional PV-10 followed by radiotherapy for localized in transit or recurrent metastatic melanoma.  ASCO 2016. # e21072.  J Clin Oncol 34, 2016.  Foote, Burmeister, Thomas, et al.  

Background: Intralesional rose bengal (IL PV-10) can elicit ablation of injected tumors and a T-cell mediated abscopal effect in untreated lesions. Phase 2 testing in patients with Stage III-IV melanoma yielded a 51% objective response rate (ORR) with 50% complete response (CR) when all disease was injected. Three patients who progressed received external beam radiotherapy (XRT) to their recurrent lesions with an impressive response without an increased radiation reaction. Methods: An open-label, single-arm phase 2 study was performed to assess efficacy and safety of IL PV-10 followed by XRT. Eligibility included recurrent localized dermal, subcutaneous, in-transit or metastatic malignant melanoma (stage IIIb / IIIc) suitable for intralesional therapy and XRT. Patients received a single course of PV-10 into lesions treatable within a localized radiotherapy field. If CR was not achieved patients received 30 Gy (6 fractions of 5 Gy twice weekly over 3 weeks) 3D conformal radiotherapy (photons or electrons) commencing 6-10 weeks after PV-10. Outcome assessments included ORR and clinical benefit (CR+PR+SD) of in-field target lesions by RECIST criteria, toxicity using CTCAE V3.0, and progression free survival (PFS). Results: There were 15 patients enrolled with 13 completing the radiotherapy component. Two patients had rapidly progressive distant disease following PV-10 injection. The mean age of patients was 69 years. With a median follow up duration of 19.3 months the overall response rate was 87% with 93% clinical benefit on an intent-to-treat basis. The mean time to best response was 3.8 months, mean duration of complete response (PFS) 12.2 months, overall loco regional progression rate 80% and melanoma specific survival 65.5 months.  Size of metastases (less than 10mm) predicted potential for lesion complete response. Treatments were well tolerated with no treatment associated grade 4 or 5 adverse events. Conclusions: The combination of IL PV-10 and radiotherapy resulted in lesion specific, normal tissue sparing, ablation of melanoma tumors with minimal local or systemic adverse effects. The study results justify expanded evaluation in a randomized trial.

Wow!!! Good luck, ratties! - c

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