Iván Márquez-Rodas, Caroline Dutriaux, Philippe Saiag, Luis de la Cruz Merino, Eduardo Castañón Álvarez, Caroline Robert, Juan F Rodríguez-Moreno, Ana Arance, Pablo Cerezuela-Fuentes, Henri Montaudié, Miguel F Sanmamed, María González-Cao, Julie Charles, María Pilar López Criado, Alfonso Berrocal, Enrique de Miguel, Elisa Funck-Brentano, Sorilla Prey, Mᵃ Carmen Álamo de la Gala, Ignacio Melero, Jose Antonio Avilés-Izquierdo, Ruth Roman, Beatriz Garcia-Pelaez, Sonia Rodriguez, Zuzana Jirakova Trnkova, Marisol Quintero, Sonia Maciá, Marya F Chaney, Stephane Dalle
{"title":"BO-112 + Pembrolizumab治疗抗pd -1耐药晚期黑色素瘤：II期临床试验SPOTLIGHT-203","authors":"Iván Márquez-Rodas, Caroline Dutriaux, Philippe Saiag, Luis de la Cruz Merino, Eduardo Castañón Álvarez, Caroline Robert, Juan F Rodríguez-Moreno, Ana Arance, Pablo Cerezuela-Fuentes, Henri Montaudié, Miguel F Sanmamed, María González-Cao, Julie Charles, María Pilar López Criado, Alfonso Berrocal, Enrique de Miguel, Elisa Funck-Brentano, Sorilla Prey, Mᵃ Carmen Álamo de la Gala, Ignacio Melero, Jose Antonio Avilés-Izquierdo, Ruth Roman, Beatriz Garcia-Pelaez, Sonia Rodriguez, Zuzana Jirakova Trnkova, Marisol Quintero, Sonia Maciá, Marya F Chaney, Stephane Dalle","doi":"10.1200/JCO-24-02595","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Patients with anti-PD-1-resistant melanoma (MEL) have no well-defined standard of care. BO-112 is a synthetic, double-stranded RNA (poly I:C) nanoplexed with polyethylenimine that when administered intratumorally has showed in patients with solid tumors potential to revert this resistance. We report efficacy and safety of the phase II clinical trial of intratumoral BO-112 plus intravenous pembrolizumab for patients with anti-PD-1-resistant MEL (ClinicalTrials.gov identifier: NCT04570332).</p><p><strong>Methods: </strong>Forty-two patients were treated with intratumoral BO-112 once every week for 7 weeks and then once every 3 weeks (up to 2 mg and up to eight lesions per treatment) combined with 200 mg pembrolizumab once every 3 weeks until progressive disease, unacceptable toxicity, death, or up to 1 year. Primary end point was RECIST 1.1 objective response rate (ORR) by independent central radiology review in modified intention-to-treat population (mITT; patients evaluable for response) with 20% ORR positivity threshold. Secondary key end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.</p><p><strong>Results: </strong>For mITT, there were 40 patients and the ORR was 25%, with 10% complete, 15% partial, and 40% stable disease, with nonachieved (NA) median DOR (95% CI, 8.3 to NA). For ITT, there were 42 patients, and the median PFS and OS were 3.7 months (95% CI, 2.2 to 9.2) and NA (95% CI, 9.9 to NA), respectively, with 54% patients alive at 24 months. The combination was well tolerated: 16 patients (38.1%) experiencing ≥G3-4 adverse events, four (9.5%) drug-related, and no deaths related to treatment.</p><p><strong>Conclusion: </strong>The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti-PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti-PD-1-resistant scenario, with promising OS data.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402595"},"PeriodicalIF":42.1000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203.\",\"authors\":\"Iván Márquez-Rodas, Caroline Dutriaux, Philippe Saiag, Luis de la Cruz Merino, Eduardo Castañón Álvarez, Caroline Robert, Juan F Rodríguez-Moreno, Ana Arance, Pablo Cerezuela-Fuentes, Henri Montaudié, Miguel F Sanmamed, María González-Cao, Julie Charles, María Pilar López Criado, Alfonso Berrocal, Enrique de Miguel, Elisa Funck-Brentano, Sorilla Prey, Mᵃ Carmen Álamo de la Gala, Ignacio Melero, Jose Antonio Avilés-Izquierdo, Ruth Roman, Beatriz Garcia-Pelaez, Sonia Rodriguez, Zuzana Jirakova Trnkova, Marisol Quintero, Sonia Maciá, Marya F Chaney, Stephane Dalle\",\"doi\":\"10.1200/JCO-24-02595\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Patients with anti-PD-1-resistant melanoma (MEL) have no well-defined standard of care. BO-112 is a synthetic, double-stranded RNA (poly I:C) nanoplexed with polyethylenimine that when administered intratumorally has showed in patients with solid tumors potential to revert this resistance. We report efficacy and safety of the phase II clinical trial of intratumoral BO-112 plus intravenous pembrolizumab for patients with anti-PD-1-resistant MEL (ClinicalTrials.gov identifier: NCT04570332).</p><p><strong>Methods: </strong>Forty-two patients were treated with intratumoral BO-112 once every week for 7 weeks and then once every 3 weeks (up to 2 mg and up to eight lesions per treatment) combined with 200 mg pembrolizumab once every 3 weeks until progressive disease, unacceptable toxicity, death, or up to 1 year. Primary end point was RECIST 1.1 objective response rate (ORR) by independent central radiology review in modified intention-to-treat population (mITT; patients evaluable for response) with 20% ORR positivity threshold. Secondary key end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.</p><p><strong>Results: </strong>For mITT, there were 40 patients and the ORR was 25%, with 10% complete, 15% partial, and 40% stable disease, with nonachieved (NA) median DOR (95% CI, 8.3 to NA). For ITT, there were 42 patients, and the median PFS and OS were 3.7 months (95% CI, 2.2 to 9.2) and NA (95% CI, 9.9 to NA), respectively, with 54% patients alive at 24 months. The combination was well tolerated: 16 patients (38.1%) experiencing ≥G3-4 adverse events, four (9.5%) drug-related, and no deaths related to treatment.</p><p><strong>Conclusion: </strong>The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti-PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti-PD-1-resistant scenario, with promising OS data.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"JCO2402595\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO-24-02595\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO-24-02595","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203.
Purpose: Patients with anti-PD-1-resistant melanoma (MEL) have no well-defined standard of care. BO-112 is a synthetic, double-stranded RNA (poly I:C) nanoplexed with polyethylenimine that when administered intratumorally has showed in patients with solid tumors potential to revert this resistance. We report efficacy and safety of the phase II clinical trial of intratumoral BO-112 plus intravenous pembrolizumab for patients with anti-PD-1-resistant MEL (ClinicalTrials.gov identifier: NCT04570332).
Methods: Forty-two patients were treated with intratumoral BO-112 once every week for 7 weeks and then once every 3 weeks (up to 2 mg and up to eight lesions per treatment) combined with 200 mg pembrolizumab once every 3 weeks until progressive disease, unacceptable toxicity, death, or up to 1 year. Primary end point was RECIST 1.1 objective response rate (ORR) by independent central radiology review in modified intention-to-treat population (mITT; patients evaluable for response) with 20% ORR positivity threshold. Secondary key end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.
Results: For mITT, there were 40 patients and the ORR was 25%, with 10% complete, 15% partial, and 40% stable disease, with nonachieved (NA) median DOR (95% CI, 8.3 to NA). For ITT, there were 42 patients, and the median PFS and OS were 3.7 months (95% CI, 2.2 to 9.2) and NA (95% CI, 9.9 to NA), respectively, with 54% patients alive at 24 months. The combination was well tolerated: 16 patients (38.1%) experiencing ≥G3-4 adverse events, four (9.5%) drug-related, and no deaths related to treatment.
Conclusion: The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti-PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti-PD-1-resistant scenario, with promising OS data.
期刊介绍：
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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