In my role as a Clinical Professor of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Professor of Medicine and Director of Early Phase Clinical Trials Program in the Department of Medicine at Roswell Park Comprehensive Cancer Center, I am developing novel therapies for patients with cancer. This includes clinical trials from early pre-clinical phase through phase I/II/III with emphasis on combination of immune and targeted agents, novel drug design, including histology-agnostic trial development of targeted therapies. I also provide advice on regulatory requirements and necessary steps associated with advancing drugs, devices and imaging agents toward clinical trials in patients.
In my professional career, I have focused both on developing precision medicine agents as well as immunotherapies. In the first in human trial of PLX4032/vemurafenib our team has provided critical PK/PD data that led to the first in class/ first in human FDA-approved BRAF inhibitor. My interest and expertise in immunotherapy started in early 1990s with animal models of IL-2 and IL-15 cytokines and natural killer cell development, continued with high dose IL-2 studies and subsequently Phase I-III trials with both CTLA-4 and PD1/PDL-1 checkpoint inhibitors. Our team was instrumental in the development of talimogene laherparepvec, the first in human oncolytic virus therapy for patients with melanoma. Recently, we have explored immunotherapy combinations with targeted agents as well as combinations of oncolytic viruses with checkpoint inhibitors .
Our work was instrumental in several FDA approvals of breakthrough anti-cancer drugs (vemurafenib, dabrafenib+trametinib, vemurafenib+cobimetinib, pembrolizumab, talimogene laherparepvec) and resulted in almost 100 manuscripts, including New England Journal of Medicine, Lancet, Journal of Clinical Oncology, JAMA, Nature. I am a member of American Society of Medical Oncology, Society of Immunotherapy in Cancer, ACP, AACR and Society of Melanoma Research and serve as an editor and reviewer for several peer reviewed journals.
- Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O’Dwyer PJ, Lee RJ, Grippo JF, Nolop K, and Chapman, PB. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010, 26;363(9):809-19 PMID:20818844
- Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, Leming P, Puzanov I, Shin, D, Kirkwood JM. Ipilimumab plus sargramostim vs. ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014;312(17):1744-1753. doi:10.1001/jama.2014.13943
- Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, Schachter J, Pavlick AC, Lewis KD, Cranmer LD, Blank CU, O'Day SJ, Ascierto PA, Salama AK, Margolin KA, Loquai C, Eigentler TK, Gangadhar TC, Carlino MS, Agarwala SS, Moschos SJ, Sosman JA, Goldinger SM, Shapira-Frommer R, Gonzalez R, Kirkwood JM, Wolchok JD, Eggermont A, Li XN, Zhou W, Zernhelt AM, Lis J, Ebbinghaus S, Kang SP, Daud A. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomized, controlled, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):908-18. doi: 10.1016/S1470-2045(15)00083-2. Epub 2015 Jun 23. PMID: 26115796
- Hyman DM*, Puzanov I*, Subbiah V*, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J^, Baselga J^. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015 Aug 20;373(8):726-36. doi: 10.1056/NEJMoa1502309. PMID: 26287849 *DMH, IP and VS contributed equally, ^JT, JB contributed equally
- Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, Chastain M, Gorski KS, Anderson A, Chou J, Kaufman HL, Andtbacka RH. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol. 2016 Aug 1;34(22):2619-26. doi: 10.1200/JCO.2016.67.1529. Epub 2016 Jun 13. PMID: 27298410