University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Alain Algazi, MD

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 Summary

My 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.

Education

Education
UCLA School of Medicine 2004

Residencies
UCLA Medical Center, Internal Medicine 2007

Fellowships
UCSF Medical Center, Hematology and Oncology 2010

Selected Publications

  1. Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, Demelo S, Margolin K. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 08 23; 379(8):722-730.
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  2. Xu MJ, Wu TJ, van Zante A, El-Sayed IH, Algazi AP, Ryan WR, Ha PK, Yom SS. Mortality risk after clinical management of recurrent and metastatic adenoid cystic carcinoma. J Otolaryngol Head Neck Surg. 2018 Apr 25; 47(1):28.
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  3. Xu MJ, Lazar AA, Garsa AA, Arron ST, Ryan WR, El-Sayed IH, George JR, Algazi AP, Heaton CM, Ha PK, Yom SS. Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy. Head Neck. 2018 Mar 10.
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  4. Cohen RB, Delord JP, Doi T, Piha-Paul SA, Liu SV, Gilbert J, Algazi AP, Damian S, Hong RL, Le Tourneau C, Day D, Varga A, Elez E, Wallmark J, Saraf S, Thanigaimani P, Cheng J, Keam B. Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study. Am J Clin Oncol. 2018 Feb 21.
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  5. Eroglu Z, Zaretsky JM, Hu-Lieskovan S, Kim DW, Algazi A, Johnson DB, Liniker E. High response rate to PD-1 blockade in desmoplastic melanomas. Nature. 2018 Jan 18; 553(7688):347-350.
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  6. Algazi AP, Esteve-Puig R, Nosrati A, Hinds B, Hobbs-Muthukumar A, Nandoskar P, Ortiz-Urda S, Chapman PB, Daud A. Dual MEK/AKT inhibition with trametinib and GSK2141795 does not yield clinical benefit in metastatic NRAS-mutant and wild-type melanoma. Pigment Cell Melanoma Res. 2018 Jan; 31(1):110-114.
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  7. Canton DA, Shirley S, Wright J, Connolly R, Burkart C, Mukhopadhyay A, Twitty C, Qattan KE, Campbell JS, Le MH, Pierce RH, Gargosky S, Daud A, Algazi A. Melanoma treatment with intratumoral electroporation of tavokinogene telseplasmid (pIL-12, tavokinogene telseplasmid). Immunotherapy. 2017 Dec; 9(16):1309-1321.
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  8. Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20; 35(36):4050-4056.
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  9. Loo K, Tsai KK, Mahuron K, Liu J, Pauli ML, Sandoval PM, Nosrati A, Lee J, Chen L, Hwang J, Levine LS, Krummel MF, Algazi AP, Pampaloni M, Alvarado MD, Rosenblum MD, Daud AI. Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy. JCI Insight. 2017 07 20; 2(14).
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  10. Tsai KK, Algazi AP. Are PD-1 antibodies safe for use in metastatic uveal melanoma? Melanoma Manag. 2017 May; 4(2):79-82.
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  11. Tumeh PC, Hellmann MD, Hamid O, Tsai KK, Loo KL, Gubens MA, Rosenblum M, Harview CL, Taube JM, Handley N, Khurana N, Nosrati A, Krummel MF, Tucker A, Sosa EV, Sanchez PJ, Banayan N, Osorio JC, Nguyen-Kim DL, Chang J, Shintaku IP, Boasberg PD, Taylor EJ, Munster PN, Algazi AP, Chmielowski B, Dummer R, Grogan TR, Elashoff D, Hwang J, Goldinger SM, Garon EB, Pierce RH, Daud A. Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC. Cancer Immunol Res. 2017 05; 5(5):417-424.
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  12. Nosrati A, Tsai KK, Goldinger SM, Tumeh P, Grimes B, Loo K, Algazi AP, Nguyen-Kim TDL, Levesque M, Dummer R, Hamid O, Daud A. Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy. Br J Cancer. 2017 Apr 25; 116(9):1141-1147.
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  13. Algazi AP, Grandis JR. Head and neck cancer in 2016: A watershed year for improvements in treatment? Nat Rev Clin Oncol. 2017 Feb; 14(2):76-78.
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  14. 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. 2017 04 15; 23(8):1910-1919.
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  15. 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. 2017 01; 109(1).
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  16. Tsai KK, Pampaloni MH, Hope C, Algazi AP, Ljung BM, Pincus L, Daud AI. Increased FDG avidity in lymphoid tissue associated with response to combined immune checkpoint blockade. J Immunother Cancer. 2016; 4:58.
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  17. 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.
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  18. 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.
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  19. 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 01; 126(9):3447-52.
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  20. Coit DG, Thompson JA, Algazi A, Andtbacka R, Bichakjian CK, Carson WE, 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 08; 14(8):945-58.
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