American Association for Cancer Research
10780432ccr192217-sup-225121_2_supp_6174891_q935y0.docx (12.04 kB)

Supplementary Figure Legends from Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma

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posted on 2023-03-31, 22:11 authored by Alain P. Algazi, Christopher G. Twitty, Katy K. Tsai, Mai Le, Robert Pierce, Erica Browning, Reneta Hermiz, David A. Canton, Donna Bannavong, Arielle Oglesby, Murray Francisco, Lawrence Fong, Mikael J. Pittet, Sean P. Arlauckas, Christopher Garris, Lauren P. Levine, Carlos Bifulco, Carmen Ballesteros-Merino, Shailender Bhatia, Sharron Gargosky, Robert H.I. Andtbacka, Bernard A. Fox, Michael D. Rosenblum, Adil I. Daud

Supplementary Figure Legends



Tumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; “tavo”) electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL). Tavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done. The combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses. The combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors.

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