Sd-101 in combination with pembrolizumab in advanced melanoma: Results of a phase ib, multicenter study

Antoni Ribas, Theresa Medina, Shivaani Kummar, Asim Amin, Anusha Kalbasi, Joseph J. Drabick, Minal Barve, Gregory A. Daniels, Deborah J. Wong, Emmett V. Schmidt, Albert F. Candia, Robert L. Coffman, Abraham C.F. Leung, Robert S. Janssen

Research output: Contribution to journalComment/debate

28 Citations (Scopus)

Abstract

PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase Ib trial evaluated intratumoral SD-101, a synthetic CpG oligonucleotide that stimulates Toll-like receptor 9 (TLR9), in combination with pembrolizumab in patients with unresectable or metastatic malignant melanoma. The most common adverse events related to SD-101 were injection-site reactions and transient, mild-to-moderate “flu-like” symptoms. Among the 9 patients naïve to anti–PD-1 therapy, the overall response rate (ORR) was 78%. The estimated 12-month progression-free survival rate was 88%, and the overall survival rate was 89%. Among 13 patients having prior anti–PD-1 therapy, the ORR was 15%. RNA profiling of tumor biopsies demonstrated increased CD8+ T cells, natural killer cells, cytotoxic cells, dendritic cells, and B cells. The combination of intratumoral SD-101 and pembrolizumab was well tolerated and induced broad immune activation in the tumor microenvironment with durable tumor responses in both peripheral and visceral lesions. SIGNIFICANCE: These early data demonstrate that the combination of pembrolizumab with intratumoral SD-101 is well tolerated and can induce immune activation at the tumor site. Combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially increase clinical efficacy with minimal additional toxicity relative to PD-1 blockade alone.

Original languageEnglish (US)
JournalCancer Discovery
Volume8
Issue number10
DOIs
StatePublished - Oct 2018

Fingerprint

Toll-Like Receptor 9
Multicenter Studies
Melanoma
Survival Rate
Neoplasms
Tumor Microenvironment
Oligonucleotides
Natural Killer Cells
Dendritic Cells
Disease-Free Survival
B-Lymphocytes
RNA
T-Lymphocytes
Biopsy
Injections
Therapeutics
pembrolizumab

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Ribas, Antoni ; Medina, Theresa ; Kummar, Shivaani ; Amin, Asim ; Kalbasi, Anusha ; Drabick, Joseph J. ; Barve, Minal ; Daniels, Gregory A. ; Wong, Deborah J. ; Schmidt, Emmett V. ; Candia, Albert F. ; Coffman, Robert L. ; Leung, Abraham C.F. ; Janssen, Robert S. / Sd-101 in combination with pembrolizumab in advanced melanoma : Results of a phase ib, multicenter study. In: Cancer Discovery. 2018 ; Vol. 8, No. 10.
@article{9e430176ae244e17a53c93db01f46684,
title = "Sd-101 in combination with pembrolizumab in advanced melanoma: Results of a phase ib, multicenter study",
abstract = "PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase Ib trial evaluated intratumoral SD-101, a synthetic CpG oligonucleotide that stimulates Toll-like receptor 9 (TLR9), in combination with pembrolizumab in patients with unresectable or metastatic malignant melanoma. The most common adverse events related to SD-101 were injection-site reactions and transient, mild-to-moderate “flu-like” symptoms. Among the 9 patients na{\"i}ve to anti–PD-1 therapy, the overall response rate (ORR) was 78{\%}. The estimated 12-month progression-free survival rate was 88{\%}, and the overall survival rate was 89{\%}. Among 13 patients having prior anti–PD-1 therapy, the ORR was 15{\%}. RNA profiling of tumor biopsies demonstrated increased CD8+ T cells, natural killer cells, cytotoxic cells, dendritic cells, and B cells. The combination of intratumoral SD-101 and pembrolizumab was well tolerated and induced broad immune activation in the tumor microenvironment with durable tumor responses in both peripheral and visceral lesions. SIGNIFICANCE: These early data demonstrate that the combination of pembrolizumab with intratumoral SD-101 is well tolerated and can induce immune activation at the tumor site. Combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially increase clinical efficacy with minimal additional toxicity relative to PD-1 blockade alone.",
author = "Antoni Ribas and Theresa Medina and Shivaani Kummar and Asim Amin and Anusha Kalbasi and Drabick, {Joseph J.} and Minal Barve and Daniels, {Gregory A.} and Wong, {Deborah J.} and Schmidt, {Emmett V.} and Candia, {Albert F.} and Coffman, {Robert L.} and Leung, {Abraham C.F.} and Janssen, {Robert S.}",
year = "2018",
month = "10",
doi = "10.1158/2159-8290.CD-18-0280",
language = "English (US)",
volume = "8",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

Ribas, A, Medina, T, Kummar, S, Amin, A, Kalbasi, A, Drabick, JJ, Barve, M, Daniels, GA, Wong, DJ, Schmidt, EV, Candia, AF, Coffman, RL, Leung, ACF & Janssen, RS 2018, 'Sd-101 in combination with pembrolizumab in advanced melanoma: Results of a phase ib, multicenter study', Cancer Discovery, vol. 8, no. 10. https://doi.org/10.1158/2159-8290.CD-18-0280

Sd-101 in combination with pembrolizumab in advanced melanoma : Results of a phase ib, multicenter study. / Ribas, Antoni; Medina, Theresa; Kummar, Shivaani; Amin, Asim; Kalbasi, Anusha; Drabick, Joseph J.; Barve, Minal; Daniels, Gregory A.; Wong, Deborah J.; Schmidt, Emmett V.; Candia, Albert F.; Coffman, Robert L.; Leung, Abraham C.F.; Janssen, Robert S.

In: Cancer Discovery, Vol. 8, No. 10, 10.2018.

Research output: Contribution to journalComment/debate

TY - JOUR

T1 - Sd-101 in combination with pembrolizumab in advanced melanoma

T2 - Results of a phase ib, multicenter study

AU - Ribas, Antoni

AU - Medina, Theresa

AU - Kummar, Shivaani

AU - Amin, Asim

AU - Kalbasi, Anusha

AU - Drabick, Joseph J.

AU - Barve, Minal

AU - Daniels, Gregory A.

AU - Wong, Deborah J.

AU - Schmidt, Emmett V.

AU - Candia, Albert F.

AU - Coffman, Robert L.

AU - Leung, Abraham C.F.

AU - Janssen, Robert S.

PY - 2018/10

Y1 - 2018/10

N2 - PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase Ib trial evaluated intratumoral SD-101, a synthetic CpG oligonucleotide that stimulates Toll-like receptor 9 (TLR9), in combination with pembrolizumab in patients with unresectable or metastatic malignant melanoma. The most common adverse events related to SD-101 were injection-site reactions and transient, mild-to-moderate “flu-like” symptoms. Among the 9 patients naïve to anti–PD-1 therapy, the overall response rate (ORR) was 78%. The estimated 12-month progression-free survival rate was 88%, and the overall survival rate was 89%. Among 13 patients having prior anti–PD-1 therapy, the ORR was 15%. RNA profiling of tumor biopsies demonstrated increased CD8+ T cells, natural killer cells, cytotoxic cells, dendritic cells, and B cells. The combination of intratumoral SD-101 and pembrolizumab was well tolerated and induced broad immune activation in the tumor microenvironment with durable tumor responses in both peripheral and visceral lesions. SIGNIFICANCE: These early data demonstrate that the combination of pembrolizumab with intratumoral SD-101 is well tolerated and can induce immune activation at the tumor site. Combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially increase clinical efficacy with minimal additional toxicity relative to PD-1 blockade alone.

AB - PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase Ib trial evaluated intratumoral SD-101, a synthetic CpG oligonucleotide that stimulates Toll-like receptor 9 (TLR9), in combination with pembrolizumab in patients with unresectable or metastatic malignant melanoma. The most common adverse events related to SD-101 were injection-site reactions and transient, mild-to-moderate “flu-like” symptoms. Among the 9 patients naïve to anti–PD-1 therapy, the overall response rate (ORR) was 78%. The estimated 12-month progression-free survival rate was 88%, and the overall survival rate was 89%. Among 13 patients having prior anti–PD-1 therapy, the ORR was 15%. RNA profiling of tumor biopsies demonstrated increased CD8+ T cells, natural killer cells, cytotoxic cells, dendritic cells, and B cells. The combination of intratumoral SD-101 and pembrolizumab was well tolerated and induced broad immune activation in the tumor microenvironment with durable tumor responses in both peripheral and visceral lesions. SIGNIFICANCE: These early data demonstrate that the combination of pembrolizumab with intratumoral SD-101 is well tolerated and can induce immune activation at the tumor site. Combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially increase clinical efficacy with minimal additional toxicity relative to PD-1 blockade alone.

UR - http://www.scopus.com/inward/record.url?scp=85054347406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054347406&partnerID=8YFLogxK

U2 - 10.1158/2159-8290.CD-18-0280

DO - 10.1158/2159-8290.CD-18-0280

M3 - Comment/debate

C2 - 30154193

AN - SCOPUS:85054347406

VL - 8

JO - Cancer Discovery

JF - Cancer Discovery

SN - 2159-8274

IS - 10

ER -