Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice

Tjulandin, S.; Демидов, Лев В.; Moiseyenko, Vladimir; Проценко, Светлана; Semiglazova, Tatiana; Odintsova, Svetlana; Zukov, Ruslan; Lazarev, Sergey; Makarova, Yuliya; Nechaeva, Marina; Сакаева, Д. Д.; Andreev, Aleksey; Tarasova, Anna; Fadeyeva, Natalya; Shustova, Mariia; Kuryshev, Ivan V.

doi:10.1016/j.ejca.2021.02.030

Cited by 29 publications

(22 citation statements)

References 26 publications

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“…The current focus of research lies on newer and hopefully more efficient immune checkpoint inhibitors. Tjulandin et al reported results of the MIRACULUM study, exploring the potential of prolgolimab, an advanced anti-PD-1 ( programmed cell death protein 1) monoclonal antibody at two different dosing schemes [ 76 ]. An objective intracranial response was seen in approximately 50%, and the averaged OS of the patients with brain metastases was 11 months.…”

Section: Resultsmentioning

confidence: 99%

State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain

et al. 2022

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In 1999 a visionary short article by The Wall Street Journal writers Robert Langreth and Michael Waldholz popularized the new term “personalized medicine,” that is to say, the targeting of drugs to each unique genetic profile. From today’s perspective, targeted approaches have clearly found the widest use in the antineoplastic domain. The current review was initiated to review the progress that has been made regarding the treatment of patients with advanced cancer and brain metastases. PubMed was searched for the terms brain metastasis, brain metastases, or metastatic brain in the Title/Abstract. Selection was limited to randomized controlled trial (RCT) and publication date January 2010 to February 2022. Following visual review, 51 papers on metastatic lung cancer, 12 on metastatic breast cancer, and 9 on malignant melanoma were retained and underwent full analysis. Information was extracted from the papers giving specific numbers for intracranial response rate and/or overall survival. Since most pharmacological trials on advanced cancers excluded patients with brain metastases and since hardly any information on adjuvant radiotherapy and radiosurgery is available from the pharmacological trials, precise assessment of the effect of targeted medication for the subgroups with brain metastases is difficult. Some quantitative information regarding the success of targeted pharmacological therapy is only available for patients with breast and lung cancer and melanoma. Overall, targeted approaches approximately doubled the lifespan in the subgroups of brain metastases from tumors with targetable surface receptors such as anaplastic lymphoma kinase (ALK) fusion receptor in non-small cell lung cancer or human epidermal growth factor receptor 2 (HER2)–positive breast cancer. For these types, overall survival in the situation of brain metastases is now more than a year. For receptor-negative lung cancer and melanoma, introduction of immune checkpoint blockers brought a substantial advance, although overall survival for melanoma metastasized to the brain appears to remain in the range of 6 to 9 months. The outlook for small cell lung cancer metastasized to the brain apparently remains poor. The introduction of targeted therapy roughly doubled survival times of advanced cancers including those metastasized to the brain, but so far, targeted therapy does not differ essentially from chemotherapy, therefore also facing tumors developing escape mechanisms. With the improved perspective of patients suffering from brain metastases, it becomes important to further optimize treatment of this specific patient group within the framework of randomized trials.

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Section: Resultsmentioning

confidence: 99%

State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain

et al. 2022

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“…Важным этапом эволюции терапевтических моноклональных антител стало появление антител на основе IgG1 с генно-инженерной мутацией LALA (L234A/L235A) в Fc-фрагменте [17]. МКА с мутацией LALA (пролголимаб) связываются с рецептором FcγRI в значительно меньшей степени по сравнению с антителами IgG4 с заменой S228P [18].…”

Section: Conflict Of Interestunclassified

“…Таким образом, антитела к PD-1 с мутацией LALA могут обладать потенциальными преимуществами при проведении анти-PD-1-терапии за счет предотвращения взаимодействия между Fc-фрагментом и FcγR, экспрессируемыми на различных иммунных клетках, в результате чего блокируются возможные эффекторные функции этих антител [17].…”

Section: Conflict Of Interestunclassified

Key differences between anti-PD-1/PD-L1 inhibitors

et al. 2022

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Indications to immunotherapy in cancer treatment continue to expand, thus there are more and more questions about clinical aspects of using different checkpoint inhibitors. Despite similar mechanism of action between widely used antibodies to PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (durvalumab, avelumab, atezolizumab), inhibitors are different due to features of monoclonal antibodies structure they are based on. For instance, toxicity leading to discontinuation of treatment occurs more frequently with anti-PD-L1 drugs than PD-1 inhibitors. On the contrary, the average incidence of any grade IRAEs was higher in patients treated with anti-PD-1 drugs. The revealed differences in the toxicity of the analyzed groups of drugs could be associated with the type of action of the drug. The feature of the PD-L1 inhibitors is more frequent occurrence of antibody-dependent cellular cytotoxicity reactions. However, PD-1 inhibitors showed a statistically significant survival benefit, according to a meta-analysis comparing anti-PD-1 and anti-PD-L1 groups. Besides data on differences in the efficacy and toxicity profiles of these agents, in this article we also analyze different issues in the structure of drug molecules, in particular, the role of LALA mutation in anti-PD-1 inhibitors. Understanding the key distinctive points of check-point inhibitors (CPI) in the future may allow to solve the problem of rechallenge and reintroduction after management of severe IRAEs.

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“…In 2021, two additional FDA approvals were granted: tisotumab vedotin for second-line r/mCC and pembrolizumab combined with chemotherapy ± bevacizumab for first-line PD-L1-positive persistent or r/ mCC. With at least 2 dozen additional immunotherapies in clinical trials (Table 1) [31][32][33][34][35][36][37][38][39], the treatment landscape for cervical cancer is on the verge of a paradigm shift. Multiple compounds are in various stages of development that examine the potential for improvement in efficacy and safety in different treatment lines and cervical cancer stages.…”

Section: Introductionmentioning

confidence: 99%

Integration of immunotherapy into treatment of cervical cancer: Recent data and ongoing trials

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Enomoto²,

Kast

et al. 2022

Cancer Treatment Reviews

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Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice

Cited by 29 publications

References 26 publications

State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain

State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain

Key differences between anti-PD-1/PD-L1 inhibitors

Integration of immunotherapy into treatment of cervical cancer: Recent data and ongoing trials

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