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Ref Type Journal Article
PMID (31455681)
Authors Doi T, Muro K, Ishii H, Kato T, Tsushima T, Takenoyama M, Oizumi S, Gemmoto K, Suna H, Enokitani K, Kawakami T, Nishikawa H, Yamamoto N
Title A Phase I Study of the Anti-CC Chemokine Receptor 4 Antibody, Mogamulizumab, in Combination with Nivolumab in Patients with Advanced or Metastatic Solid Tumors.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 25
Issue 22
Date 2019 Nov 15
URL
Abstract Text Regulatory T cells (Tregs) expressing CC chemokine receptor 4 (CCR4) can suppress antitumor immune responses and are associated with poor prognoses in several cancers. We assessed the safety and efficacy of combined mogamulizumab (anti-CCR4 antibody) and nivolumab [anti-programmed death-1 (PD-1) antibody] in immunotherapy-naïve patients with advanced/metastatic solid tumors.This study (NCT02476123) comprised dose-escalation (3+3 design) and expansion parts. Patients received nivolumab (3.0 mg/kg) every 2 weeks, with mogamulizumab (0.3 or 1.0 mg/kg in dose escalation, 1.0 mg/kg in expansion) once weekly for 4 weeks, then every 2 weeks, until progression or unacceptable toxicity. Primary objective was safety; secondary objectives were antitumor effects, pharmacokinetics, and immunogenicity. Exploratory biomarker analyses were conducted.Ninety-six patients were enrolled (July 2015-November 2016): six patients in the dose-escalation part and 90 in the expansion part. No dose-limiting toxicities were observed in the dose-escalation part. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 29% of patients in the expansion part (no grade 5 TRAEs). The most frequent TRAEs were rash (39%), rash maculopapular (20%), diarrhea (13%), stomatitis (12%), and pruritus (11%). There were four (27%) confirmed tumor responses among 15 patients with hepatocellular carcinoma, and one confirmed and two unconfirmed responses among 15 patients with pancreatic adenocarcinoma. During treatment, populations of effector Tregs (CD4+CD45RA-FoxP3high) decreased and CD8+ T cells in tumor-infiltrating lymphocytes increased.Combining an anti-PD-1 antibody, nivolumab, with a Treg-depleting anti-CCR4 antibody, mogamulizumab, provides an acceptable safety profile, antitumor activity, and a potentially effective option in cancer immunotherapy.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown lung small cell carcinoma not applicable Mogamulizumab + Nivolumab Phase I Actionable In a Phase I trial, Poteligeo (mogamulizumab-kpkc) and Opdivo (nivolumab) combination treatment demonstrated acceptable safety, resulted in an objective response rate of 7% (1/15, 1 partial responses) and a disease control rate of 20% (3/15) in immunotherapy-naive patients with advanced or metastatic small cell lung cancer, response occurred regardless of PD-L1, CCR4, CD8 expression levels and tumor mutational burden (PMID: 31455681; NCT02476123). 31455681
Unknown unknown hepatocellular carcinoma not applicable Mogamulizumab + Nivolumab Phase I Actionable In a Phase I trial, Poteligeo (mogamulizumab-kpkc) and Opdivo (nivolumab) combination treatment demonstrated acceptable safety, resulted in an objective response rate of 27% (4/15, 4 partial responses) and a disease control rate of 67% (10/15) in immunotherapy-naive patients with advanced or metastatic hepatocellular carcinoma, response occurred regardless of PD-L1, CCR4, CD8 expression levels and tumor mutational burden (PMID: 31455681; NCT02476123). 31455681
Unknown unknown pancreatic adenocarcinoma not applicable Mogamulizumab + Nivolumab Phase I Actionable In a Phase I trial, Poteligeo (mogamulizumab-kpkc) and Opdivo (nivolumab) combination treatment demonstrated acceptable safety, resulted in an objective response rate of 7% (1/15, 1 partial responses) and a disease control rate of 40% (6/15) in immunotherapy-naive patients with advanced or metastatic pancreatic adenocarcinoma, response occurred regardless of PD-L1, CCR4, CD8 expression levels and tumor mutational burden (PMID: 31455681; NCT02476123). 31455681
Unknown unknown esophageal cancer not applicable Mogamulizumab + Nivolumab Phase I Actionable In a Phase I trial, Poteligeo (mogamulizumab-kpkc) and Opdivo (nivolumab) combination treatment demonstrated acceptable safety, resulted in an objective response rate of 13% (3/15, 2 partial responses) and a disease control rate of 33% (5/15) in immunotherapy-naive patients with advanced or metastatic esophageal cancer, response occurred regardless of PD-L1, CCR4, CD8 expression levels and tumor mutational burden (PMID: 31455681; NCT02476123). 31455681
Unknown unknown stomach cancer not applicable Mogamulizumab + Nivolumab Phase I Actionable In a Phase I trial, Poteligeo (mogamulizumab-kpkc) and Opdivo (nivolumab) combination treatment demonstrated acceptable safety, resulted in an objective response rate of 0% (0/15) and a disease control rate of 27% (4/15) in immunotherapy-naive patients with advanced or metastatic gastric cancer, response occurred regardless of PD-L1, CCR4, CD8 expression levels and tumor mutational burden (PMID: 31455681; NCT02476123). 31455681
Unknown unknown lung non-small cell carcinoma not applicable Mogamulizumab + Nivolumab Phase I Actionable In a Phase I trial, Poteligeo (mogamulizumab-kpkc) and Opdivo (nivolumab) combination treatment demonstrated acceptable safety, resulted in an objective response rate of 20% (3/15, 3 partial responses) and a disease control rate of 40% (6/15) in immunotherapy-naive patients with advanced or metastatic non-small cell lung cancer, response occurred regardless of PD-L1, CCR4, CD8 expression levels and tumor mutational burden (PMID: 31455681; NCT02476123). 31455681