First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments.

Background: Tumor-selective oncolytic viral vectors are promising anticancer therapeutics; however, challenges with dosing and potency in advanced/metastatic cancers have limited efficacy and usage. NG-350A is a next-generation blood-stable adenoviral vector engineered to express an agonist anti-cluster of differentiation (CD)40 antibody without affecting tumor-selectivity and oncolytic potency.

Methods: Intravenous and intratumoral (IT) administration of NG-350A was assessed in a phase Ia/Ib study in patients with metastatic/advanced epithelial tumors (NCT03852511).

The Potential of Real-Time Behavior and Well-Being Assessments to Improve Medical Student Wellness.

Problem: Medical students experience psychological distress more frequently than age-matched peers. Tracking medical student well-being has typically been limited to once- or twice-per-year questionnaires. Ongoing, real-time assessment of student behavior and well-being could facilitate individualized, timely interventions.

Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced/metastatic epithelial cancer: a phase I clinical trial (SPICE).

Background: Novel combination therapies to overcome anti-PD-1 resistance are required. Enadenotucirev, a tumor-selective blood stable adenoviral vector, has demonstrated a manageable safety profile and ability to increase tumor immune-cell infiltration in phase I studies in solid tumors.

Methods: We conducted a phase I multicenter study of intravenous enadenotucirev plus nivolumab in patients with advanced/metastatic epithelial cancer not responding to standard therapy.

A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies.

Tumor-selective viruses are a novel therapeutic approach for treating cancer. Tumor-Specific Immuno Gene Therapy (T-SIGn) vectors are tumor-selective adenoviral vectors designed to express immunomodulatory transgenes. Prolonged activated partial thromboplastin time (aPTT), associated with the presence of antiphospholipid antibodies (aPL), has been observed in patients with viral infections, and following administration of adenovirus-based medicines.

Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion-Positive Lung Cancers.

Purpose: Larotrectinib is a highly selective and CNS-active tropomyosin receptor kinase (TRK) inhibitor that has demonstrated efficacy across TRK fusion-positive cancers, regardless of the tumor type. The aim of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion-positive lung cancers.

Materials And Methods: Data from two global, multicenter, registrational clinical trials of patients treated with larotrectinib were analyzed: a phase II adult and young adult basket trial (NCT02576431) and a phase I adult trial (NCT02122913).

Impact of a Palliative Care Nurse Practitioner in an Oncology Clinic: A Quality Improvement Effort.

Purpose: Guidelines support early integration of palliative care (PC) into standard oncology practice; however, little is known as to whether outcomes can be improved by modifying health care delivery in a real-world setting.

Methods: We report our 6-year experience of embedding a nurse practitioner in an oncology clinic (March 2014-March 2020) to integrate early, concurrent advance care planning and PC.

Results: Compared with patients with advanced cancer not enrolled in the palliative care nurse practitioner program, in March 2020, patients who are enrolled are more likely to have higher quality of PC (eg, goals of care note documentation [82% 15%; < .

Therapeutic targeting of SLC6A8 creatine transporter suppresses colon cancer progression and modulates human creatine levels.

Colorectal cancer (CRC) is a leading cause of cancer mortality. Creatine metabolism was previously shown to critically regulate colon cancer progression. We report that RGX-202, an oral small-molecule SLC6A8 transporter inhibitor, robustly inhibits creatine import in vitro and in vivo, reduces intracellular phosphocreatine and ATP levels, and induces tumor apoptosis.

A phase I, open-label study evaluating the safety and pharmacokinetics of trifluridine/tipiracil in patients with advanced solid tumors and varying degrees of renal impairment.

Purpose: Trifluridine/tipiracil (FTD/TPI) is approved for advanced colorectal and gastric/gastroesophageal cancer; however, data in patients with renal impairment (RI) are limited. This phase I study evaluated FTD/TPI in patients with advanced solid tumors and varying degrees of RI to develop dosing guidance.

Methods: Patients were enrolled into normal renal function (CrCl ≥ 90 mL/min), mild RI (CrCl 60-89 mL/min), or moderate RI (CrCl 30-59 mL/min) cohorts and administered the recommended FTD/TPI dose (35 mg/m twice daily, days 1-5 and 8-12; 28-day cycle).

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort.

Objectives: Blockade of programmed cell death-1 (PD-1) and its ligand (PD-L1) has transformed the treatment of NSCLC. In a first-in-human, Phase 1, dose escalation and cohort expansion study, cemiplimab, a monoclonal antibody directed against PD-1, was evaluated for the treatment of patients with advanced solid tumors (NCT02383212). Here, we report results in patients with advanced NSCLC from the dose expansion cohort.

Tracking medical student emotionality in relation to whole body dissection and donation.

Introduction: For students studying anatomy, dissection of the human body can elicit a wide range of intellectual and emotional responses that are subject to change over the duration of a course. The purpose of this study was to determine how overall emotional responses change over time, if there are differences in responses by gender and previous laboratory exposure, and if these responses impact course performance.

Methods: First-year medical students enrolled in the Human Structure and Function course at the University of Vermont, and in the Organ Systems 1, 2, and 3 courses at Morehouse School of Medicine were given a series of four surveys across the first-year curriculum.

First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies.

Purpose: This first-in-human study assessed the safety, tolerability, dose-limiting toxicities (DLT), antitumor activity, and pharmacokinetics of cemiplimab, a monoclonal anti-programmed cell death-1 (PD-1), as monotherapy and in combination with hypofractionated radiotherapy (hfRT) and/or cyclophosphamide (CPA) in patients with advanced solid tumors.

Patients And Methods: Patients were enrolled in 1 of 10 dose escalation cohorts and received cemiplimab 1, 3, or 10 mg/kg every 2 weeks intravenously for up to 48 weeks. Depending on the cohort, patients received hfRT and/or low-dose (200 mg/m) CPA.

Working with Older Adults Scale: Application of the Theory of Planned Behavior.

Background And Objectives: The expanding population of older adults in the United States, coupled with provider hesitance to work with this population, is expected to result in a large service gap, particularly in the health care field. Research on provider hesitancy has largely focused on the impact of attitudes toward older adults and professional competency, with some recent explorations of social influences. There is currently no comprehensive measure that includes all of these areas.

Sharing personal information about anatomical body donors: What first-year medical students want to know and how it affects emotional responses to dissection.

Among educators who teach in the human anatomy laboratory, there has been lively debate about sharing information about anatomical donors. One consideration in this debate is concern about the emotional effect of personalizing donors on the students. The purpose of this study was to evaluate student responses to being exposed to donor information (DI).

A phase I, dose-escalation study of PF-06650808, an anti-Notch3 antibody-drug conjugate, in patients with breast cancer and other advanced solid tumors.

Background PF-06650808 is a novel anti-Notch3 antibody-drug conjugate (ADC) able to deliver an auristatin-based cytotoxic payload to target cells. In this first-in-human, dose-finding, phase I study (NCT02129205), we investigated safety, pharmacokinetics, immunogenicity, and preliminary antitumor activity of single-agent PF-06650808 in 40 patients with advanced breast cancer (BC) and other solid tumors unselected for Notch3 expression. Primary endpoint was dose-limiting toxicity (DLT).

Open-label study to evaluate trifluridine/tipiracil safety, tolerability and pharmacokinetics in patients with advanced solid tumours and hepatic impairment.

Aims: Trifluridine/tipiracil (FTD/TPI) prolongs survival in refractory metastatic colorectal cancer, but limited data exist on its use in patients with hepatic impairment. This Phase I, open-label, nonrandomized study investigated the safety, tolerability and pharmacokinetics of FTD/TPI in patients with advanced solid tumours (except breast cancer) and varying degrees of hepatic impairment, to provide dosing recommendations.

Methods: Patients aged ≥18 years with advanced solid tumours and normal hepatic function, or mild, moderate or severe hepatic impairment according to National Cancer Institute criteria, were planned to be enrolled.

Phase I study of the anti-α5β1 monoclonal antibody MINT1526A with or without bevacizumab in patients with advanced solid tumors.

Purpose: MINT1526A is a monoclonal antibody that blocks the interaction of integrin alpha 5 beta 1 (α5β1) with its extracellular matrix ligands. This phase I study evaluated the safety and pharmacokinetics of MINT1526A with or without bevacizumab in patients with advanced solid tumors.

Methods: MINT1526A was administered every 3 weeks (Q3W) as monotherapy (arm 1) or in combination with bevacizumab 15 mg/kg, Q3W (arm 2).

Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours.

This corrects the article DOI: 10.1038/bjc.2017.

Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer.

Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor LY3007113 in patients with advanced cancer to establish a recommended phase 2 dose. Methods In part A (dose escalation), LY3007113 was administered orally every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle until the maximum tolerated dose (MTD) was reached.

Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours.

Background: Hyaluronan accumulation in tumour stroma is associated with reduced survival in preclinical cancer models. PEGPH20 degrades hyaluronan to facilitate tumour access for cancer therapies. Our objective was to assess safety and antitumour activity of PEGPH20 in patients with advanced solid tumours.

Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars.

Colorectal cancer (CRC) is a leading cause of tumor-related morbidity and mortality worldwide, with mortality most often attributable to metastatic disease. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, has a significant role in the treatment of metastatic CRC (mCRC). However, patient access to bevacizumab may be limited in some regions or circumstances, owing to factors related to insurance coverage, reimbursement, patient out-of-pocket costs, or availability.

A phase 1 study of the pharmacokinetics of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (components of TAS-102) vs trifluridine alone.

Background Trifluridine, a thymidine-based chemotherapeutic, has limited bioavailability after clinical administration as it is rapidly degraded via thymidine phosphorylase. An oral combination tablet combines trifluridine with a potent thymidine phosphorylase inhibitor, tipiracil hydrochloride. This study's objective was to evaluate whether trifluridine/tipiracil (TAS-102) administration increases trifluridine exposure vs trifluridine alone.