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Ref Type | Journal Article | ||||||||||||
PMID | (32586937) | ||||||||||||
Authors | Zamarin D, Hamid O, Nayak-Kapoor A, Sahebjam S, Sznol M, Collaku A, Fox FE, Marshall MA, Hong DS | ||||||||||||
Title | Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study. | ||||||||||||
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Abstract Text | The study goal was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-C-C chemokine receptor 4 (anti-CCR4) mAb targeting effector regulatory T cells (eTreg), in combination with mAb checkpoint inhibitors durvalumab or tremelimumab.This was a multicenter, phase I, dose escalation study, followed by disease-specific cohort expansion (NCT02301130). Mogamulizumab dose escalation proceeded with concurrent dose escalation of durvalumab or tremelimumab in patients with advanced solid tumors. Cohort expansion occurred with mogamulizumab 1 mg/kg plus durvalumab 10 mg/kg or tremelimumab 10 mg/kg in patients with advanced pancreatic cancer.Forty patients were enrolled during dose escalation, followed by 24 patients during dose expansion. No dose-limiting toxicities occurred during dose escalation. No new or unexpected toxicities were seen. Tolerability, the primary endpoint, was acceptable utilizing mogamulizumab 1 mg/kg plus durvalumab or tremelimumab 10 mg/kg in the combined dose escalation and dose expansion cohorts (each n = 19). At these doses, the objective response rate was 5.3% (95% confidence interval, 0.1%-26.0%; one partial response) with each combination treatment. At all doses, mogamulizumab treatment led to almost complete depletion of peripheral eTregs, as well as reduction of intratumoral Tregs in the majority of patients. There was no clear correlation of clinical response with peripheral or intratumoral reduction in CCR4+ eTregs or with baseline degree of CCR4+ expression.Mogamulizumab in combination with durvalumab or tremelimumab did not result in potent antitumor efficacy in patients with advanced solid tumors. Tolerability of mogamulizumab 1 mg/kg combined with durvalumab or tremelimumab 10 mg/kg was acceptable. |
Molecular Profile | Treatment Approach |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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Tremelimumab | Tremelimumab | 0 | 27 |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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Tremelimumab | Imjudo | CP-675,206|Ticilimumab|CP-675206 | CTLA4 Antibody 29 Immune Checkpoint Inhibitor 147 | Imjudo (tremelimumab) binds to and inhibits cytotoxic T-lymphocyte-associated protein 4 (CTLA4), thereby enhancing T-cell activation by blocking CTLA4-mediated inhibition of T-cell activation (PMID: 32620213, PMID: 32586937). Imjudo (tremelimumab) is FDA approved for use in combination with Imfinzi (durvalumab) in adult patients with unresectable hepatocellular carcinoma, and in combination with Imfinzi (durvalumab) and platinum-based chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC) without sensitizing EGFR or ALK mutations (FDA.gov). |
Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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