Tilsotolimod with Ipilimumab Drives Tumor Responses in Anti–PD-1 Refractory Melanoma
| العنوان: | Tilsotolimod with Ipilimumab Drives Tumor Responses in Anti–PD-1 Refractory Melanoma |
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| المؤلفون: | Salah-Eddine Bentebibel, Willem W. Overwijk, Montaser Shaheen, Marc Uemura, Courtney W. Hudgens, Marihella James, Ravi Murthy, Gary C. Doolittle, Robert H.I. Andtbacka, Chantale Bernatchez, Michael A. Davies, S. Chunduru, Douglas B. Johnson, Daniel H. Johnson, Igor Puzanov, Patrick Hwu, Shah Rahimian, Cara Haymaker, Adi Diab, Joseph Markowitz, Denái R. Milton, Michael T. Tetzlaff, Sudhir Agrawal, Nashat Gabrail, Houssein Safa |
| المصدر: | Cancer Discov |
| بيانات النشر: | American Association for Cancer Research (AACR), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Skin Neoplasms, Antigen presentation, Ipilimumab, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Adverse effect, Immune Checkpoint Inhibitors, Melanoma, Aged, Aged, 80 and over, business.industry, Dendritic cell, Middle Aged, Gene signature, medicine.disease, United States, Immune checkpoint, Clinical trial, Treatment Outcome, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, medicine.drug |
| الوصف: | Many patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase I/II trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, with systemic ipilimumab in patients with anti–PD-1– resistant advanced melanoma. In all patients, 48.4% experienced grade 3/4 treatment-emergent adverse events. The overall response rate at the recommended phase II dose of 8 mg was 22.4%, and an additional 49% of patients had stable disease. Responses in noninjected lesions and in patients expected to be resistant to ipilimumab monotherapy were observed. Rapid induction of a local IFNα gene signature, dendritic cell maturation and enhanced markers of antigen presentation, and T-cell clonal expansion correlated with clinical response. A phase III clinical trial with this combination (NCT03445533) is ongoing. Significance: Despite recent developments in advanced melanoma therapies, most patients do not experience durable responses. Intratumoral tilsotolimod injection elicits a rapid, local type 1 IFN response and, in combination with ipilimumab, activates T cells to promote clinical activity, including in distant lesions and patients not expected to respond to ipilimumab alone. This article is highlighted in the In This Issue feature, p. 1861 |
| تدمد: | 2159-8290 2159-8274 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b6b8d46d46d9fa5dab66b18718b3d64Test https://doi.org/10.1158/2159-8290.cd-20-1546Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7b6b8d46d46d9fa5dab66b18718b3d64 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21598290 21598274 |
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