Alain Algazi, MD
Associate Professor, Department of Medicine (Hematology/Oncology), UCSF
Program Leader, UCSF Head and Neck Medical Oncology
Melanoma Specialist, UCSF Medical Center
Research SummaryMy research interests are currently focused on enhancing anti-tumor immune responses in patients with advanced melanoma and head andneck cancer. Anti-tumor immune responses induced by PD-1 antibodies can be limited by inadequate tumor infiltration by effector T-cells, the presence of regulatory cells, or the absence of pro-inflammatory cytokine in the tumor. To bridge this gap, I have been leading clinical trials of intratumoral plasmid injection followed by electroporation. This approach allows the intratumoral elaboration of IL12 without the significant toxicity. Intratumoral treatment with plasmid IL-12 and electroporation (IT-pIL12-EP) can induce TIL infiltration and cytokine elaboration. This, in turn, can lead to regression of both injected and uninjected lesions in metastatic melanoma patients with extensive in-transit lesions. Our group also demonstrated that IT-pIL12-EP can prime tumors to respond to PD-1 antibodies and I am currently leading clinical efforts to combine IT-pIL12-EP with pembrolizumab in melanoma patients in a phase 2 clinical trial. The plasmid electroporation platform also allows intratumoral transduction of plasmid DNA coding for additional immune modulators and next-generation plasmids are currently under development. Our group also pioneered the use of IT-pIL12-EP in patients with advanced squamous cell carcinoma of the head and neck.
After gaining clinical trials experience in melanoma and building a busy clinical practice in both melanoma and head and neck oncology, I was named as UCSF’s Program Leader for Head and Neck Medical Oncology as well as Chair of the Head and Neck Research Committee. I am currently developing a portfolio trials focused on immune therapy in squamous cell carcinoma of the head and neck. There are currently a large number of PD-1 antibody trials in clinical development, but pre-clinical data thatcould help prioritize these trials is lacking. I am currently collaboratingwith Jim Keck at the Jackson Laboratory to develop a new mouse model with ahumanized immune system to facilitate evaluation of immune therapy combinations optimized for use in humans.
In addition to my work on immune therapy, I am also the national study chair for a clinical trial of continuous versus intermittentdosing of dabrafenib and trametinib in BRAF inhibitor naïve patients with BRAF mutant melanoma. This trial is based on the finding that BRAF mutant melanoma tumors that become resistant to BRAF inhibitors may become dependent on continued drug exposure for survival. In this model, dose interruptions were associated with tumor regressions and maintained BRAF inhibitor sensitivity. S1320 was developed to test this hypothesis in patients.
UCLA School of Medicine 2004
UCLA Medical Center, Internal Medicine 2007
UCSF Medical Center, Hematology and Oncology 2010
- Rosen LS, Goldman JW, Algazi AP, Turner PK, Moser B, Hu T, Wang XA, Tuttle J, Wacheck V, Wooldridge JE, Banck M. A First-in-Human Phase I Study of a Bivalent MET Antibody, Emibetuzumab (LY2875358), as Monotherapy and in Combination with Erlotinib in Advanced Cancer. Clin Cancer Res. 2016 Oct 10. pii: clincanres.1418.2016. [Epub ahead of print]
- Shoushtari AN, Munhoz RR, Kuk D, Ott PA, Johnson DB, Tsai KK, Rapisuwon S, Eroglu Z, Sullivan RJ, Luke JJ, Gangadhar TC, Salama AK, Clark V, Burias C, Puzanov I, Atkins MB, Algazi AP, Ribas A, Wolchok JD, Postow MA. The efficacy of anti-PD-1 agents in acral and mucosal melanoma. Cancer. 2016 Nov 15;122(21):3354-3362. doi: 10.1002/cncr.30259.
- Algazi AP, Tsai KK, Shoushtari AN, Munhoz RR, Eroglu Z, Piulats JM, Ott PA, Johnson DB, Hwang J, Daud AI, Sosman JA, Carvajal RD, Chmielowski B, Postow MA, Weber JS, Sullivan RJ.Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016 Nov 15;122(21):3344-3353. doi: 10.1002/cncr.30258.
- Faden DL, Algazi A. Durable treatment of ameloblastoma with single agent BRAFi Re: Clinical and radiographic response with combined BRAF-targeted therapy in stage 4 ameloblastoma. J Natl Cancer Inst. 2016 Sep 26;109(1). pii: djw190. No abstract available.
- Tsai KK, Pampaloni MH, Hope C, Algazi AP, Ljung BM, Pincus L, Daud AI. Increased FDG avidity in lymphoidtissue associated with response to combined immune checkpoint blockade. J Immunother Cancer. 2016 Sep 20;4:58. doi: 10.1186/s40425-016-0162-9.
- Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, Algazi AP, Pampaloni MH, Lobach IV, Hwang J, Pierce RH, Gratz IK, Krummel MF, Rosenblum MD.Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016 Sep 1;126(9):3447-52. doi: 10.1172/JCI87324.
- Coit DG, Thompson JA, Algazi A, Andtbacka R, Bichakjian CK, Carson WE 3rd, Daniels GA, DiMaio D, Fields RC, Fleming MD, Gastman B, Gonzalez R, Guild V, Johnson D,Joseph RW, Lange JR, Martini MC, Materin MA, Olszanski AJ, Ott P, Gupta AP,Ross MI, Salama AK, Skitzki J, Swetter SM, Tanabe KK, Torres-Roca JF, Trisal V, Urist MM, McMillian N, Engh A. NCCN Guidelines Insights: Melanoma, Version 3.2016. J Natl Compr Canc Netw. 2016 Aug;14(8):945-58.
- Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, Patnaik A, Hwu WJ, Weber JS, Gangadhar TC, Hersey P, Dronca R, Joseph RW, Zarour H, Chmielowski B, Lawrence DP, AlgaziA, Rizvi NA, Hoffner B, Mateus C, Gergich K, Lindia JA, Giannotti M, Li XN, Ebbinghaus S, Kang SP, Robert C. Association of Pembrolizumab WithTumor Response and Survival Among Patients With Advanced Melanoma. JAMA. 2016 Apr 19;315(15):1600-9. doi: 10.1001/jama.2016.4059. Erratum in: JAMA. 2016 Jun 14;315(22):2472.
- Coit DG, Thompson JA, Algazi A, Andtbacka R, Bichakjian CK, Carson WE 3rd, Daniels GA, DiMaio D, Ernstoff M, Fields RC, Fleming MD, Gonzalez R, Guild V, Halpern AC, Hodi FS Jr, Joseph RW, Lange JR, Martini MC, Materin MA, Olszanski AJ, Ross MI, Salama AK, Skitzki J, Sosman J, Swetter SM, Tanabe KK, Torres-Roca JF, Trisal V, Urist MM, McMillian N, Engh A. Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. JNatl Compr Canc Netw. 2016 Apr;14(4):450-73.
- Long GV, Weber JS, Infante JR, Kim KB, Daud A, Gonzalez R, Sosman JA, Hamid O, Schuchter L, Cebon J, Kefford RF, Lawrence D, Kudchadkar R, Burris HA 3rd, Falchook GS, Algazi A, Lewis K, Puzanov I, Ibrahim N, Sun P, Cunningham E, Kline AS, Del Buono H, McDowell DO, Patel K, Flaherty KT. Overall Survival and Durable Responses in Patients With BRAF V600-Mutant MetastaticMelanoma Receiving Dabrafenib Combined With Trametinib. J Clin Oncol. 2016 Mar 10;34(8):871-8. doi: 10.1200/JCO.2015.62.9345.
- Sanlorenzo M, Vujic I, Daud A, Algazi A, Gubens M, Luna SA, Lin K, Quaglino P, Rappersberger K, Ortiz-Urda S. Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression. JAMA Dermatol. 2015 Nov;151(11):1206-12. doi: 10.1001/jamadermatol.2015.1916.
- Algazi AP, Cha E, Ortiz-Urda SM, McCalmont T, Bastian BC, Hwang J, Pampaloni MH, Behr S, Chong K, Cortez B, Quiroz A, Coakley F, Liu S, Daud AI. The combination of axitinib followed by paclitaxel/carboplatin yields extended survival in advanced BRAF wild-type melanoma: results of a clinical/correlative prospective phase II clinical trial. Br J Cancer. 2015 Apr 14;112(8):1326-31. doi: 10.1038/bjc.2014.541.
- Raleigh DR, Algazi A, Arron ST, Neuhaus IM, Yom SS. Induction Hedgehog pathway inhibition followed by combined-modality radiotherapy for basal cell carcinoma. Br J Dermatol. 2015 Aug;173(2):544-6. doi:10.1111/bjd.13748.
- Lin L, Sabnis AJ, Chan E, Olivas V, Cade L, Pazarentzos E, Asthana S, Neel D, Yan JJ, Lu X, Pham L, Wang MM, Karachaliou N, Cao MG, Manzano JL, Ramirez JL, Torres JM, Buttitta F, Rudin CM, Collisson EA, Algazi A, Robinson E, Osman I, Muñoz-Couselo E, Cortes J, Frederick DT, Cooper ZA, McMahon M, Marchetti A, Rosell R, Flaherty KT, Wargo JA, Bivona TG. The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies. Nat Genet.2015 Mar;47(3):250-6. doi: 10.1038/ng.3218.
- Moriceau G, Hugo W, Hong A, Shi H, Kong X, Yu CC, Koya RC, Samatar AA, Khanlou N, Braun J, Ruchalski K, Seifert H, Larkin J, Dahlman KB, Johnson DB, Algazi A, Sosman JA, Ribas A, Lo RS. Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction. Cancer Cell. 2015 Feb 9;27(2):240-56. doi: 10.1016/j.ccell.2014.11.018.
- Sanlorenzo M, Choudhry A, Vujic I, Posch C, Chong K, Johnston K, Meier M, Osella-Abate S,Quaglino P, Daud A, Algazi A, Rappersberger K, Ortiz-Urda S. Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma. J Am Acad Dermatol. 2014 Dec;71(6):1102-1109.e1. doi: 10.1016/j.jaad.2014.09.002.
- Johnson DB, Flaherty KT, Weber JS, Infante JR, Kim KB, Kefford RF, Hamid O, Schuchter L, Cebon J, Sharfman WH, McWilliams RR, Sznol M, Lawrence DP, Gibney GT, Burris HA 3rd, Falchook GS, Algazi A, Lewis K, Long GV, Patel K, Ibrahim N, Sun P, Little S, Cunningham E, Sosman JA, Daud A, Gonzalez R. Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-agent BRAF inhibitor. J Clin Oncol. 2014 Nov 20;32(33):3697-704. doi: 10.1200/JCO.2014.57.3535.
- Sanlorenzo M, Vujic I, Posch C, Dajee A, Yen A, Kim S, Ashworth M, Rosenblum MD, Algazi A, Osella-Abate S, Quaglino P, Daud A, Ortiz-Urda S. Melanoma immunotherapy. Cancer Biol Ther. 2014 Jun 1;15(6):665-74. doi: 10.4161/cbt.28555. Review.
- Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133.
- Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin AM, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Nov;13(11):1087-95. doi: 10.1016/S1470-2045(12)70431-X.
- Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, Hamid O, Schuchter L,Cebon J, Ibrahim N, Kudchadkar R, Burris HA 3rd, Falchook G, Algazi A, Lewis K, Long GV, Puzanov I, Lebowitz P, Singh A, Little S, Sun P, Allred A, Ouellet D, Kim KB, Patel K, Weber J. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012 Nov;367(18):1694-703. doi: 10.1056/NEJMoa1210093.
- Algazi AP, Weber JS, Andrews SC, Urbas P, Munster PN, DeConti RC, Hwang J, Sondak VK, Messina JL, McCalmont T, Daud AI. Phase I clinical trial of the Srcinhibitor dasatinib with dacarbazine in metastatic melanoma. Br J Cancer. 2012 Jan 3;106(1):85-91. doi: 10.1038/bjc.2011.514.
- DeConti RC, Algazi AP, Andrews S, Urbas P, Born O, Stoeckigt D, Floren L, Hwang J, Weber J, Sondak VK, Daud AI. Phase II trial of sagopilone, a novel epothilone analog in metastatic melanoma. Br J Cancer. 2010 Nov 9;103(10):1548-53. doi: 10.1038/sj.bjc.6605931.
- Algazi AP, Kadoch C, Rubenstein JL. Biology and treatment of primary central nervous system lymphoma. Neurotherapeutics. 2009 Jul;6(3):587-97. doi: 10.1016/j.nurt.2009.04.013. Review.