Combination of intratumoural double-stranded RNA (dsRNA) BO-112 with systemic anti-PD-1 in patients with anti-PD-1 refractory cancer

Márquez-Rodas, Iván; Longo, Federico; Aix, Santiago Ponce; Jové, Maria; Rubio, Blanca; Blanco, A. Calles; Rodríguez-Ruiz, María E.; Ponz-Sarvisé, Mariano; Castañón, Eduardo; Gajate, Pablo; Sempere-Ortega, C.; Jimenez-Aguilar, E.; López-Casas, Pedro P.; Miguel, Enrique de; Ramos-Medina, Rocío; Calvo, Aitana; Martı́n, Miguel; Tersago, Dominique; Quintero, Marisol; Melero, I.

doi:10.1093/annonc/mdz451.009

Cited by 2 publications

(8 citation statements)

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“… 29 Marquez-Rodas investigated the efficacy of anti-PD-1 retreatment with intratumoral double-stranded RNA (dsRNA) for patients with advanced solid tumors showing primary resistance to anti-PD-1 inhibitors. 30 The ORR was 11% and the DCR was 72% in 18 patients who were eligible for response assessment. Another phase Ib trial applied nivolumab combined with Debio 1143 [an antagonist of inhibitor of apoptosis proteins (IAPs)] in 11 patients with advanced solid tumors.…”

Section: Resultsmentioning

confidence: 91%

“…Notably, the combination strategy could achieve an objective response in patients with primary resistance to prior ICIs. 30 As both preclinical and clinical evidence have demonstrated enhanced efficacy with combination strategies for cancer patients, 45 – 47 ICIs combined with other agents might be effective for retreatment. Currently, 14 ongoing trials are evaluating the efficacy of different combinations including ICIs combined with chemotherapy, targeted therapy, radiotherapy, or a different ICI ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

“… 11 , 12 Moreover, patients with primary resistance to prior immunotherapy could also benefit from ICI retreatment, as they showed similar ORR (11–29%) in some included studies when ICIs were switched to another type or combined with other agents. 18 , 30 Therefore, further randomized controlled trials for a non-selective population are required to identify patients who could benefit most from ICI retreatment, and more diverse treatment regimens should also be explored to identify the most effective strategy.…”

Section: Discussionmentioning

confidence: 99%

“…The preliminary outcomes of retreatment with PD-1 or PD-L1 inhibitors combined with other agents were evaluated in seven studies. [25][26][27][28][29][30][31] The ORR was 5-51%, and the DCR was 38-72%.…”

Section: Anti-pd-(l)1 Retreatment Anti-pd-(l)1 Single Agent Retreatmentmentioning

confidence: 99%

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Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review

Yang

Sun

et al. 2020

Ther Adv Med Oncol

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Background: A large proportion of patients eventually experience disease progression despite treatment with immune checkpoint inhibitors (ICIs), but subsequent treatment options are limited for this population. Retreatment with the same or different types of ICIs is a possible strategy, but the clinical efficacy and safety data are limited. This systematic review aims to evaluate the efficacy and safety of ICIs retreatment in patients with solid tumors after disease progression to previous ICIs. Methods: We searched MEDLINE, EMBASE, the Cochrane Library, and major meeting libraries for prospective studies. The primary outcomes included the objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), and the incidence of grade ⩾3 immune-related adverse events (irAEs). Results: We identified 22 prospective studies including 1865 patients. For disease progression after CTLA-4 inhibitors, three studies evaluated anti-CTLA-4 retreatment. The ORR was 12–23%, the DCR was 48.4–67.7%, and the mOS was 12 months. The incidence of grade ⩾3 irAEs was 5.9–25%. Four studies evaluated anti-programmed cell death protein 1 (PD-1) retreatment. The ORR was 22–36%, the DCR was 40–64%, and the mOS was 13.4–20.6 months. The incidence of grade ⩾3 irAEs was <10%. For disease progression after PD-(L)1 inhibitors, 13 studies evaluated anti-PD-(L)1 retreatment. The ORR was 5–53%, the DCR was 38–83%, and the mOS was 13.9 months. The incidence of grade ⩾3 irAEs was 0–15% for patients retreated with single anti-PD-(L)1 agent, but was higher (0–64%) for those retreated with ICIs combined with other agents. Two studies evaluated anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) retreatment. The ORR was 0–22.4%, the DCR was 50–72%, and the mOS was 4–21 months. The incidence of grade ⩾3 irAEs was 26–61%. Conclusion: Retreatment with ICIs is feasible for cancer patients considering its encouraging efficacy and tolerable safety. Further prospective trials are needed to explore more promising strategies and identify suitable populations for retreatment.

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Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Anti-pd-(l)1 Retreatment Anti-pd-(l)1 Single Agent Retreatmentmentioning

confidence: 99%

See 2 more Smart Citations

Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review

Yang

Sun

et al. 2020

Ther Adv Med Oncol

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“…Taking this a step further, responses were improved again when Flt3 and poly I:C were used in conjunction with PD-L1 blockade and B-Raf proto-oncogene (BRAF) blockade [ 34 ], two commonly used treatments in the clinic. Overall, given that combination treatments have been more effective in preclinical studies, intratumoural TLR3 agonists like BO-112 are currently being investigated in patients with solid tumours in combination with systemic anti-PD-1 (NCT02828098; NCT04508140; NCT02423863) [ 123 ].…”

Section: Intratumoural Prr Ligands and The Tmementioning

confidence: 99%

Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists

Burn

Prasit

Hermans

2020

Cancers

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Signalling through pattern recognition receptors (PRRs) leads to strong proinflammatory responses, enhancing the activity of antigen presenting cells and shaping adaptive immune responses against tumour associated antigens. Unfortunately, toxicities associated with systemic administration of these agonists have limited their clinical use to date. Direct injection of PRR agonists into the tumour can enhance immune responses by directly modulating the cells present in the tumour microenvironment. This can improve local antitumour activity, but importantly, also facilitates systemic responses that limit tumour growth at distant sites. As such, this form of therapy could be used clinically where metastatic tumour lesions are accessible, or as neoadjuvant therapy. In this review, we summarise current preclinical data on intratumoural administration of PRR agonists, including new strategies to optimise delivery and impact, and combination studies with current and promising new cancer therapies.

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Combination of intratumoural double-stranded RNA (dsRNA) BO-112 with systemic anti-PD-1 in patients with anti-PD-1 refractory cancer

Cited by 2 publications

References 0 publications

Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review

Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review

Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists

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