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. Plonowska-Hirschfeld KA, Gulati A, Stephens EM, Ochoa E, Xu MJ, Ha PK, Heaton CM, Yom SS, Chan JW, Algazi A, Kang H, Ryan WR. Treatment Modality Impact on Patient-Reported Quality of Life in Human Papilloma Virus-Associated Oropharyngeal Carcinoma. Laryngoscope. 2023 Sep 28.  View on PubMed
  2. Gulati A, Plonowska-Hirschfeld K, Stephens EM, Kansara S, Zebolsky AL, Ochoa E, Xu MJ, Ha PK, Heaton CM, Yom SS, Chan JW, Algazi AP, Kang H, Ryan WR. A prospective evaluation of neck and shoulder function following treatments of early-stage human papillomavirus-associated oropharynx cancer. Clin Otolaryngol. 2023 Sep; 48(5):756-765.  View on PubMed
  3. Rahim MK, Okholm TLH, Jones KB, McCarthy EE, Liu CC, Yee JL, Tamaki SJ, Marquez DM, Tenvooren I, Wai K, Cheung A, Davidson BR, Johri V, Samad B, O'Gorman WE, Krummel MF, van Zante A, Combes AJ, Angelo M, Fong L, Algazi AP, Ha P, Spitzer MH. Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell. 2023 03 16; 186(6):1127-1143.e18.  View on PubMed
  4. Oh DY, Algazi A, Capdevila J, Longo F, Miller W, Chun Bing JT, Bonilla CE, Chung HC, Guren TK, Lin CC, Motola-Kuba D, Shah M, Hadoux J, Yao L, Jin F, Norwood K, Lebellec L. Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Cancer. 2023 04 15; 129(8):1195-1204.  View on PubMed
  5. Aggarwal C, Saba NF, Algazi A, Sukari A, Seiwert TY, Haigentz M, Porosnicu M, Bonomi M, Boyer J, Esser MT, Cheng LI, Agrawal S, Jennings EC, Durham NM, Fraser K, Lissa D, Gong M, Ceaicovscaia N, Gascó Hernández A, Kumar R. Safety and Efficacy of MEDI0457 plus Durvalumab in Patients with Human Papillomavirus-Associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2023 02 01; 29(3):560-570.  View on PubMed
  6. Chan ATC, Lee VHF, Hong RL, Ahn MJ, Chong WQ, Kim SB, Ho GF, Caguioa PB, Ngamphaiboon N, Ho C, Aziz MASA, Ng QS, Yen CJ, Soparattanapaisarn N, Ngan RK, Kho SK, Tiambeng MLA, Yun T, Sriuranpong V, Algazi AP, Cheng A, Massarelli E, Swaby RF, Saraf S, Yuan J, Siu LL. Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial. Ann Oncol. 2023 03; 34(3):251-261.  View on PubMed
  7. Babiker H, Borazenci E, Subbiah V, Agarwala S, Algazi A, Schachter J, Lotem M, Maurice-Dror C, Hendler D, Rahimian S, Minderman H, Haymaker C, Mahadevan D, Bernatchez C, Murthy R, Hultsch R, Kaplan N, Woodhead G, Hennemeyer C, Chunduru S, Anderson PM, Diab A, Puzanov I. Tilsotolimod Exploits the TLR9 Pathway to Promote Antigen Presentation and Type 1 IFN Signaling in Solid Tumors: A Multicenter International Phase I/II Trial (ILLUMINATE-101). Clin Cancer Res. 2022 Dec 01; 28(23):5079-5087.  View on PubMed
  8. Naing A, Algazi AP, Falchook GS, Creelan BC, Powderly J, Rosen S, Barve M, Mettu NB, Triozzi PL, Hamm J, Zhou G, Walker C, Dong Z, Patel MR. Phase 1/2 study of epacadostat in combination with durvalumab in patients with metastatic solid tumors. Cancer. 2023 01 01; 129(1):71-81.  View on PubMed
  9. 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-γ and IL-12. Immunity. 2022 Sep 13; 55(9):1749.  View on PubMed
  10. Zheng YJ, Ho W, Sanlorenzo M, Vujic I, Daud A, Algazi A, Rappersberger K, Ortiz-Urda S. Melanoma risk during immunomodulating treatment. Melanoma Res. 2022 12 01; 32(6):411-418.  View on PubMed
  11. Han M, Nguyen B, Lee JY, Browning E, Zhang J, Mukhopadhyay A, Gujar R, Salazar J, Hermiz R, Svenson L, Rolig AS, Redmond WL, Algazi AP, Daud AI, Canton DA, Twitty CG. Intratumoral Electroporation of Plasmid Encoded IL12 and Membrane-Anchored Anti-CD3 Increases Systemic Tumor Immunity. Mol Cancer Res. 2022 06 03; 20(6):983-995.  View on PubMed
  12. Lee JY, Nguyen B, Mukhopadhyay A, Han M, Zhang J, Gujar R, Salazar J, Hermiz R, Svenson L, Browning E, Lyerly HK, Canton DA, Fisher D, Daud A, Algazi A, Skitzki J, Twitty CG. Amplification of the CXCR3/CXCL9 axis via intratumoral electroporation of plasmid CXCL9 synergizes with plasmid IL-12 therapy to elicit robust anti-tumor immunity. Mol Ther Oncolytics. 2022 Jun 16; 25:174-188.  View on PubMed
  13. Cohen EEW, Nabell L, Wong DJ, Day T, Daniels GA, Milhem M, Deva S, Jameson M, Guntinas-Lichius O, Almubarak M, Strother M, Whitman E, Chisamore M, Obiozor C, Bagulho T, Gomez-Romo J, Guiducci C, Janssen R, Gamelin E, Algazi AP. Intralesional SD-101 in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naïve Head and Neck Squamous Cell Carcinoma: Results from a Multicenter, Phase II Trial. Clin Cancer Res. 2022 03 15; 28(6):1157-1166.  View on PubMed
  14. Taylor MH, Betts CB, Maloney L, Nadler E, Algazi A, Guarino MJ, Nemunaitis J, Jimeno A, Patel P, Munugalavadla V, Tao L, Adkins D, Goldschmidt JH, Cohen EEW, Coussens LM. Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study. Clin Cancer Res. 2022 Mar 01; 28(5):903-914.  View on PubMed
  15. Tawbi HA, Forsyth PA, Hodi FS, Algazi AP, Hamid O, Lao CD, Moschos SJ, Atkins MB, Lewis K, Postow MA, Thomas RP, Glaspy J, Jang S, Khushalani NI, Pavlick AC, Ernstoff MS, Reardon DA, Kudchadkar R, Tarhini A, Chung C, Ritchings C, Durani P, Askelson M, Puzanov I, Margolin KA. Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol. 2021 12; 22(12):1692-1704.  View on PubMed
  16. Tawbi HA, Forsyth PA, Hodi FS, Lao CD, Moschos SJ, Hamid O, Atkins MB, Lewis K, Thomas RP, Glaspy JA, Jang S, Algazi AP, Khushalani NI, Postow MA, Pavlick AC, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Tarhini AA, Sumbul A, Rizzo JI, Margolin KA. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. 2021 11 02; 23(11):1961-1973.  View on PubMed
  17. Wang Y, Liu S, Yang Z, Algazi AP, Lomeli SH, Wang Y, Othus M, Hong A, Wang X, Randolph CE, Jones AM, Bosenberg MW, Byrum SD, Tackett AJ, Lopez H, Yates C, Solit DB, Ribas A, Piva M, Moriceau G, Lo RS. Anti-PD-1/L1 lead-in before MAPK inhibitor combination maximizes antitumor immunity and efficacy. Cancer Cell. 2021 10 11; 39(10):1375-1387.e6.  View on PubMed
  18. 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. Author Correction: PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma. Nat Commun. 2021 Aug 12; 12(1):5022.  View on PubMed
  19. 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. Nat Commun. 2020 12 07; 11(1):6262.  View on PubMed
  20. 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. Nat Med. 2020 10; 26(10):1564-1568.  View on PubMed

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