Dataset Information

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

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 (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.

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.

SUBMITTER: Algazi AP

PROVIDER: S-EPMC9354653 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Algazi Alain P AP Twitty Christopher G CG Tsai Katy K KK Le Mai M Pierce Robert R Browning Erica E Hermiz Reneta R Canton David A DA Bannavong Donna D Oglesby Arielle A Francisco Murray M Fong Lawrence L Pittet Mikael J MJ Arlauckas Sean P SP Garris Christopher C Levine Lauren P LP Bifulco Carlos C Ballesteros-Merino Carmen C Bhatia Shailender S Gargosky Sharron S Andtbacka Robert H I RHI Fox Bernard A BA Rosenblum Michael D MD Daud Adil I AI

Clinical cancer research : an official journal of the American Association for Cancer Research 20200506 12

<h4>Purpose</h4>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).<h4>Patients and methods</h4>Tavo was administered intratumorally day ...[more]

PMID: 32376655

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Dataset Information

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

Purpose

Patients and methods

Results

Conclusions

Publications

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

Similar Datasets

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