Novel Entrectinib Trial Focuses on Gene Rearrangements Across Many Tumor Types

Excerpt:

“A decade ago, researchers believed molecular alterations occurred in only one or two cancer types. That way of thinking has changed, however, with the understanding that the same alterations, especially gene fusions, can occur across many different tumor types.

“As a result, researchers have designed a recently launched clinical study into entrectinib, a first-inclass inhibitor of tropomyosin receptor kinases (Trk), as a basket trial in which the drug can be evaluated simultaneously for activity against three gene alterations and multiple tumor types.

“STARTRK-2 (NCT02568267) is an open-label, phase II study in which patients with locally advanced or metastatic solid tumors are assigned to different baskets according to whether their tumors harbor rearrangements in one of three key genes—NTRK1/2/3, ROS1, or ALK.”

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Pexidartinib Plus Pembrolizumab Combo Tested in Ovarian and Other Solid Tumors

Excerpt:

“An ongoing clinical trial has begun the process of evaluating whether the addition of a booster agent can take the anticancer activity of PD-1 directed immunotherapy to another level.

“Investigators in a multicenter trial are evaluating the impact of pexidartinib (PLX3397)—an inhibitor of colony stimulating factor 1 (CSF1)—on the activity of the PD-1 signaling inhibitor pembrolizumab (Keytruda) in various types of solid tumors.

“The two-part phase 1/2 trial will establish a recommended dose for pexidartinib to use in combination with standard pembrolizumab dosing and then evaluate the combination in 500 patients representing 12 types of cancer.”

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New Agent Targeting Epigenetic Modifications Shows Activity in Advanced Cancer

“In a dose-escalation phase I study reported in The Lancet Oncology, Reid et al found that RRx-001, a representative of a new class of compounds called dinitroazetidines (sourced from the aerospace industry) that act on the tumor microenvironment, had activity in advanced cancers and a promising safety profile. RRx-001 is activated by hypoxia and induces generation of reactive oxygen and nitrogen species that can epigenetically modulate DNA methylation, histone deacetylation, and lysine demethylation.

“In the study, 25 patients with advanced, malignant, incurable solid tumors from the University of California, San Diego, and Sarah Cannon Research Institute received intravenous infusions of RRx-001 at increasing doses of 10 mg/m², 16.7 mg/m², 24.6 mg/m², 33 mg/m², 55 mg/m², and 83 mg/m² once or twice weekly for ≥ 4 weeks.”


The CAR T-Cell Treatment: Will It Work for Solid Tumors?


Chimeric antigen receptor (CAR) T-cell therapy is a new, immune system-based cancer treatment that has garnered recent media attention. In a clinical trial, CAR T-cell treatment left no signs of tumors in 70% to 90% of children and adults with the aggressive blood cancer acute lymphocytic leukemia (ALL). ALL is almost always fatal, and the results observed with CAR T-cell treatment are nothing short of spectacular. Continue reading…


AstraZeneca and Lilly to Collaborate on Immuno-Oncology Combination Clinical Trial in Solid Tumours

“AstraZeneca and Eli Lilly and Company (Lilly) today announced that they have entered into a clinical trial collaboration to evaluate the safety and preliminary efficacy of AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with ramucirumab (CYRAMZA®), Lilly’s VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumours.

“The Phase I study is expected to establish the safety and a recommended dosing regimen, with the potential to open expansion cohorts in various tumours of interest, for the combination of MEDI4736 and ramucirumab. Under the terms of the agreement, the trial will be sponsored by Lilly. Additional details of the collaboration, including tumour types to be studied and financial terms, were not disclosed.”


CYP3A4*22 Genotype and Systemic Exposure Affect Paclitaxel-Induced Neurotoxicity

“Paclitaxel is used for the treatment of several solid tumors and displays a high interindividual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity.”


CYP3A4*22 Genotype and Systemic Exposure Affect Paclitaxel-Induced Neurotoxicity

“Paclitaxel is used for the treatment of several solid tumors and displays a high interindividual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity.”


CYP3A4*22 Genotype and Systemic Exposure Affect Paclitaxel-Induced Neurotoxicity

“Paclitaxel is used for the treatment of several solid tumors and displays a high interindividual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity.”


Vascular Endothelial Growth Factor (VEGF) Expression in Locally Advanced Prostate Cancer: Secondary Analysis of Radiation Therapy Oncology Group (RTOG) 8610

Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer…”