Dostarlimab for the treatment of endometrium cancer and other solid tumors.

The use of monoclonal antibodies directed against programmed cell death protein 1 (PD-1) and its ligand, programmed cell death 1 ligand 1 (PD-L1), widely extends to a large number of tumors such as melanoma, non-small cell lung, renal or lymphomas, among others. Some of them are already approved as first- or second-line treatment, as pembrolizumab, nivolumab or cemiplimab. Dostarlimab is an investigational humanized anti-PD-1 that is being developed both in monotherapy and as combination therapy, for gynecological tumors but also for lung cancer or melanoma. The preliminary results, particularly in endometrial cancer, show a high affinity against PD-1 with encouraging clinical activity. Here we summarize the development of this compound as well as the current preclinical and clinical data and potential future development.

Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma.

BACKGROUND: Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor. PATIENTS AND METHODS: CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL). We report results from the dose escalation phase, which explored 11 dose levels and four dosing schedules, two weekly (2 days on/5 days off; 3 days on/4 days off), one biweekly (3 days on/11 days off), and one monthly (4 days on/24 days off). The primary objectives were to determine the safety, maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) and schedule. Secondary objectives were to evaluate signals of early antitumor activity, pharmacokinetics, and pharmacodynamics. RESULTS: This study enrolled 69 patients, 67 with solid tumors and two with diffuse large B-cell lymphoma (DLBCL). The median age was 57 years (range, 21-80) and the median number of prior regimens was four (range, 1-9). Treatment-related adverse events (TRAEs) were mostly mild and manageable; grade 3/4 TRAEs reported in more than two patients were thrombocytopenia (13%), anemia, and fatigue (4% each). Six patients had dose-limiting toxicities. MTDs were 15 mg (2 days on/5 days off), 30 mg (3 days on/11 days off), and 45 mg (4 days on/24 days off). The RP2D and schedule selected for expansion was 45 mg (4 days on/24 days off). As of 8 October 2019, one patient with grade 2 astrocytoma achieved a complete response, one patient with endometrial carcinoma had a partial response, and six patients had prolonged stable disease ≥11 months. CONCLUSIONS: CC-90010 is well tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors.

Cemiplimab for the treatment of advanced cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent type of malignancy in Caucasians worldwide. Several factors have been correlated with aggressiveness and likelihood of recurrence and distant metastases, which are challenging to control. Metastatic disease has a dismal prognosis, and standard chemotherapy has failed to significantly improve outcomes. Recently, it has been recognized that cSCCs are highly mutated tumors with a denoting potential likelihood of response to immune checkpoint blockade. Cemiplimab is an anti-programmed cell death protein 1 (PD-1) antibody recently approved for the treatment of unresectable locally advanced or metastatic cSCC by the U.S. Food and Drug Administration (FDA) and the European Commission with a compelling response rate and an acceptable safety profile.

Predictive biomarker candidates to delineate efficacy of antiangiogenic treatment in renal cell carcinoma

Antiangiogenic therapy is currently considered as the cornerstone of treatment in metastatic kidney cancer. A monoclonal antibody against the vascular endothelial growth factor (VEGF) and several tyrosine kinase inhibitors targeting the VEGF receptors demonstrated, 7 years ago, to deeply impact the outcome of this tumor and became a model of integration of molecular knowledge into clinical practice. Unfortunately, no further improvement in survival has been made and 20-25 % of cases remain primary refractory to these drugs, with an overall dismal prognosis. Since biomarker predictors of activity are lacking, their development could highly help in the process of making clinical decisions when choosing the best option for every patient or prompting the inclusion in clinical trials. This unmet medical need could become even more relevant if new immunotherapy confirms its initial promising results in this pathology. In this article, we provide an insight of current state of the art regarding the prediction of antiangiogenic efficacy in kidney cancer and propose new strategies for the implementation of such markers in clinical practice (AU)

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Predictive biomarker candidates to delineate efficacy of antiangiogenic treatment in renal cell carcinoma.

Antiangiogenic therapy is currently considered as the cornerstone of treatment in metastatic kidney cancer. A monoclonal antibody against the vascular endothelial growth factor (VEGF) and several tyrosine kinase inhibitors targeting the VEGF receptors demonstrated, 7 years ago, to deeply impact the outcome of this tumor and became a model of integration of molecular knowledge into clinical practice. Unfortunately, no further improvement in survival has been made and 20-25 % of cases remain primary refractory to these drugs, with an overall dismal prognosis. Since biomarker predictors of activity are lacking, their development could highly help in the process of making clinical decisions when choosing the best option for every patient or prompting the inclusion in clinical trials. This unmet medical need could become even more relevant if new immunotherapy confirms its initial promising results in this pathology. In this article, we provide an insight of current state of the art regarding the prediction of antiangiogenic efficacy in kidney cancer and propose new strategies for the implementation of such markers in clinical practice.