Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.
Clinical cancer research : an official journal of the American Association for Cancer Research
oregon; portland; providence cancer institute; chiles; eacri; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Female; Follow-Up Studies; Humans; Interleukin-12; Male; Melanoma; Middle Aged; Prognosis; Programmed Cell Death 1 Receptor; Prospective Studies
PURPOSE: 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).
PATIENTS AND METHODS: 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.
RESULTS: 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 (
CONCLUSIONS: 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.
Earle A. Chiles Research Institute
Algazi, Alain P; Twitty, Christopher G; Tsai, Katy K; Le, Mai; Pierce, Robert; Browning, Erica; Hermiz, Reneta; Canton, David A; Bannavong, Donna; Oglesby, Arielle; Francisco, Murray; Fong, Lawrence; Pittet, Mikael J; Arlauckas, Sean P; Garris, Christopher; Levine, Lauren P; Bifulco, Carlos; Ballesteros-Merino, Carmen; Bhatia, Shailender; Gargosky, Sharron; Andtbacka, Robert H I; Fox, Bernard A; Rosenblum, Michael D; and Daud, Adil I, "Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma." (2020). Articles, Abstracts, and Reports. 5261.