Patient Characteristics Associated with Growth of Patient-Derived Tumor Implants in Mice (Patient-Derived Xenografts).

: patient-derived xenografts (PDXs) have defined the field of translational cancer research in recent years, becoming one of the most-used tools in early drug development. The process of establishing cancer models in mice has turned out to be challenging, since little research focuses on evaluating which factors impact engraftment success. We sought to determine the clinical, pathological, or molecular factors which may predict better engraftment rates in PDXs.

BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas.

Bromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, and may play a role in cancer-cell proliferation, survival, and oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Primary endpoints were the safety, tolerability, maximum tolerated dose, and RP2D of trotabresib.

GITR Antibodies in Cancer: Not Ready for Prime Time.

Glucocorticoid-induced TNF receptor (TNFR)-related protein (GITR) agonistic antibodies are expected to increase the antitumor response mainly by reducing the effect of Foxp3+ T-regulatory cells. TRX-518 is a novel GITR agonist that has shown good pharmacodynamic activity by depleting regulatory T cells (Tregs) in preclinical models, with limited clinical activity demonstrated in patients with advanced solid tumors. See related article by Davar et al.

Increased vulnerability of clinical research units during the COVID-19 crisis and their protection.

Currently, the complexity of clinical trial development in oncology is being further complicated by the coronavirus disease 2019 (COVID-19) pandemic, which is reducing the resources needed to comply with protocol-specific procedures while putting patients in units, who are already vulnerable, at increased general risk not only for COVID-19 infection but also with respect to their baseline disease. Individualizing the management of patients while ensuring their safety and adherence to the study protocol, establishing specific staff contingency plans, and maintaining sponsor and contract research organization (CRO) alignment are some of the key issues for maintaining the continuity of cancer patients' investigational treatment and minimizing their infection risk as well as the risk to staff members of the unit, sponsors, and CROs while maintaining the integrity of data quality and compliance with good clinical practice.

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).

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.

Early Phase Clinical Trial Designs - State of Play and Adapting for the Future.

The process of anti-cancer drug development is complex, with high attrition rates. Factors that may optimise this process include well-constructed and relevant pre-clinical testing and use of biomarkers for patient selection. However, the design of early phase clinical trials will probably play a vital role in both the robust clinical investigation of new targeted therapies and in streamlining drug development.