Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

Publication Title

Clinical cancer research : an official journal of the American Association for Cancer Research

Authors

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, Earle A. Chiles Research Institute, Portland, Oregon.
Carmen Ballesteros-Merino, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA.Follow
Shailender Bhatia
Sharron Gargosky
Robert H I Andtbacka
Bernard A Fox, Chiles Research Institute Providence Portland Medical CenterFollow
Michael D Rosenblum
Adil I Daud

Document Type

Article

Publication Date

6-15-2020

Keywords

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

Abstract

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.

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Earle A. Chiles Research Institute