First-in-Class ICOS Agonist Alone or In Combination May Be Effective For Advanced Cancer
Researchers assigned patients with various types of relapsed/refractory cancer to receive escalating doses of JTX-2011 alone or plus nivolumab.
|The following article features coverage from the American Society of Clinical Oncology (ASCO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
CHICAGO—JTX-2011 — an inducible co-stimulator (ICOS) of T-cells — may be a safe and effective treatment option alone or in combination with nivolumab among patients with heavily pretreated gastric (GC) and triple-negative breast cancer (TNBC), according to findings presented at the American Society of Clinical Oncology 2018 Annual Meeting on Saturday, June 2.1
Previously conducted preclinical mouse studies demonstrated that JTX-2011 upregulated CD4 T-effector cells, depleted intratumoral T-regulatory cells, and may be effective as monotherapy or in combination with PD-1 or CTLA-4 inhibitors for tumors that have high ICOS expression.
In this first-in-human phase 1/2 ICONIC study (ClinicalTrials.gov Identifier: NCT02904226), researchers assigned 187 heavily pretreated patients with various types of relapsed/refractory cancer (including GC and TNBC) to receive escalating doses of JTX-2011 alone or plus nivolumab in phase 1, and administered the recommended phase 2 dose (0.3 mg/kg) alone or with nivolumab in phase 2.
Of the patients who received at least 1 study dose, 71 patients and 116 patients were enrolled in phase 1 and phase 2, respectively. Of the 13 patients with GC who received combination therapy who had archived and fresh biopsy samples, 6 had high ICOS expression, and 5 changed from low to high expression. Of the 7 TNBC patients treated with combination therapy with archived and fresh biopsy samples, 5 and 4 patients showed high-ICOS expression on archival and fresh biopsies, respectively.
Among 7 patients treated with JTX-2011 alone in phase 1, 1 patient with GC achieved a partial response (PR) and 2 of 5 patients with TNBC achieved stable disease (SD). Among 19 patients with GC who received JTX-2011 combination therapy in phase 1/2, 2 patients had PR and 2 had ongoing SD; 1 patient had a PR among 15 patients with TNBC in phase 2.
Of 17 evaluable patients with high ICOS expression, 1 patient who achieved PR on monotherapy, 2 patients who had PR on combination therapy, and 1 with stable disease, had an emergence of peripheral CD4 T-cells.
JTX-2011 monotherapy produced a disease control rate (DCR) of 25% and 19% in phase 1 and phase 2, respectively, and the DCR with combination treatment was 29% and 32% in phase 1 and phase 2, respectively. Results suggested that disease control and tumor reductions may associated with a high ICOS score.
JTX-2011 was well-tolerated alone or in combination with nivolumab. Observed dose-limiting toxicities occurred with the highest dose of JTX-2011 (1.0 mg/kg) alone, and included grade 3 elevated liver enzymes and pleural effusion. Two grade 5 AEs were reported among patients receiving JTX-2011 plus nivolumab: increased bilirubin and encephalopathy. In phase 2, there were drug-related, immune-related, and infusion-related adverse events.
The authors concluded that “JTX-2011 mono- and combo-therapy with nivolumab were well tolerated with antitumor responses in heavily pretreated GC and TNBC patients. Emergence of peripheral blood CD4 ICOS high T-cell subsets may be a surrogate biomarker of response. Further trials of JTX-2011 are planned.”
Read more of Cancer Therapy Advisor's coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.
- Yap TA, Burris HA, Kummar S, et al. ICONIC: Biologic and clinical activity of first in class ICOS agonist antibody JTX-2011 +/- nivolumab (nivo) in patients (pts) with advanced cancers. Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.