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. Ribas A, Algazi A, Ascierto PA, Butler MO, Chandra S, Gordon M, Hernandez-Aya L, Lawrence D, Lutzky J, Miller WH, Campbell KM, Delafont B, Marshall S, Mueller N, Robert C PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma.  View on PubMed
  2. Algazi AP, Othus M, Daud AI, Lo RS, Mehnert JM, Truong TG, Conry R, Kendra K, Doolittle GC, Clark JI, Messino MJ, Moore DF, Lao C, Faller BA, Govindarajan R, Harker-Murray A, Dreisbach L, Moon J, Grossmann KF, Ribas A Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial.  View on PubMed
  3. Levine LS, Mahuron KM, Tsai KK, Wu C, Mattis DM, Pauli ML, Oglesby A, Lee JC, Spitzer MH, Krummel MF, Algazi AP, Rosenblum MD, Alvarado M, Daud AI Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma.  View on PubMed
  4. Algazi AP, Twitty CG, Tsai KK, Le M, Pierce R, Browning E, Hermiz R, Canton DA, Bannavong D, Oglesby A, Francisco M, Fong L, Pittet MJ, Arlauckas SP, Garris C, Levine LP, Bifulco C, Ballesteros-Merino C, Bhatia S, Gargosky S, Andtbacka RHI, Fox BA, Rosenblum MD, Daud AI Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.  View on PubMed
  5. Algazi A, Bhatia S, Agarwala S, Molina M, Lewis K, Faries M, Fong L, Levine LP, Franco M, Oglesby A, Ballesteros-Merino C, Bifulco CB, Fox BA, Bannavong D, Talia R, Browning E, Le MH, Pierce RH, Gargosky S, Tsai KK, Twitty C, Daud AI Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients.  View on PubMed
  6. Greaney SK, Algazi AP, Tsai KK, Takamura KT, Chen L, Twitty CG, Zhang L, Paciorek A, Pierce RH, Le MH, Daud AI, Fong L Intratumoral Plasmid IL12 Electroporation Therapy in Patients with Advanced Melanoma Induces Systemic and Intratumoral T-cell Responses.  View on PubMed
  7. Oglesby A, Algazi AP, Daud AI Intratumoral and Combination Therapy in Melanoma and Other Skin Cancers.  View on PubMed
  8. Algazi AP, Rotow J, Posch C, Ortiz-Urda S, Pelayo A, Munster PN, Daud A A dual pathway inhibition strategy using BKM120 combined with vemurafenib is poorly tolerated in BRAF V600E/K mutant advanced melanoma.  View on PubMed
  9. Xu MJ, Plonowska KA, Gurman ZR, Humphrey AK, Ha PK, Wang SJ, El-Sayed IH, Heaton CM, George JR, Yom SS, Algazi AP, Ryan WR Treatment modality impact on quality of life for human papillomavirus-associated oropharynx cancer.  View on PubMed
  10. Chan JW, Yeh I, El-Sayed IH, Algazi AP, Glastonbury CM, Ha PK, Yom SS, van Zante A Ultraviolet light-related DNA damage mutation signature distinguishes cutaneous from mucosal or other origin for head and neck squamous cell carcinoma of unknown primary site.  View on PubMed
  11. Zandberg DP, Algazi AP, Jimeno A, Good JS, Fayette J, Bouganim N, Ready NE, Clement PM, Even C, Jang RW, Wong S, Keilholz U, Gilbert J, Fenton M, Braña I, Henry S, Remenar E, Papai Z, Siu LL, Jarkowski A, Armstrong JM, Asubonteng K, Fan J, Melillo G, Mesía R Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with =25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy.  View on PubMed
  12. Garris CS, Arlauckas SP, Kohler RH, Trefny MP, Garren S, Piot C, Engblom C, Pfirschke C, Siwicki M, Gungabeesoon J, Freeman GJ, Warren SE, Ong S, Browning E, Twitty CG, Pierce RH, Le MH, Algazi AP, Daud AI, Pai SI, Zippelius A, Weissleder R, Pittet MJ Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-? and IL-12.  View on PubMed
  13. 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.  View on PubMed
  14. 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.  View on PubMed
  15. 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.  View on PubMed
  16. 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.  View on PubMed
  17. Eroglu Z, Zaretsky JM, Hu-Lieskovan S, Kim DW, Algazi A, Johnson DB, Liniker E, Ben Kong , Munhoz R, Rapisuwon S, Gherardini PF, Chmielowski B, Wang X, Shintaku IP, Wei C, Sosman JA, Joseph RW, Postow MA, Carlino MS, Hwu WJ, Scolyer RA, Messina J, Cochran AJ, Long GV, Ribas A High response rate to PD-1 blockade in desmoplastic melanomas.  View on PubMed
  18. 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.  View on PubMed
  19. 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).  View on PubMed
  20. 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.  View on PubMed

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