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Today’s NYT

SpaceX’s latest iteration of its Starship rocket suffered a dramatic setback early Friday when an explosion ripped through an upgraded booster undergoing testing at the company’s Starbase facility in…

James Cameron created a wave of excitement after he revealed new details…

Georgina RannardClimate and science correspondent, Belém, Brazil
EPAFollowing bitter rows, the UN climate summit COP30 in Belém, Brazil has ended with a deal that contains no direct reference to the fossil fuels that are heating up the planet.
It…

With Merlin powering up, he can now hand out stronger buffs and even grant a new rod shaped by his own magic. Merlin’s Staff is one of the most valuable rods in Fisch thanks to its special effects and late-game potential. This guide…

Former Wake Forest star and 12-year NBA player Rodney Rogers has died. He was 54.
The school announced Saturday that Rogers had died on Friday. Rogers – the No. 9 overall NBA draft pick in 1993 – had been paralyzed from…

Treatment with intraventricular HER2-directed CAR T-cell therapy, with or without lymphodepletion (LD), was safe and led to stable disease (SD) in patients with HER2-positive breast cancer with recurrent brain and/or leptomeningeal metastases, according to data from a phase 1 trial (NCT03696030) presented at the
The most common adverse effects (AEs) included grade 1/2 headaches, nausea/vomiting, fever, fatigue, and myalgias lasting 24 to 48 hours following a dose of the therapy. Two instances of possible grade 1/2 immune effector cell–associated neurotoxicity syndrome occurred in 2 patients treated with LD and CAR T-cell therapy, with these patients developing confusion/lethargy. Within the LD plus CAR T-cell therapy cohort (n = 13), 2 dose-limiting toxicities (DLTs) were reported in the form of grade 3 headache, which prevented the administration of planned doses of HER2 CAR T cells.
In both cohorts, the best response was SD. Patients treated with CAR T-cell therapy alone (n = 10) achieved an SD rate of 44% with a median duration of SD of 56 days (range, 50-136). In patients treated with LD plus CAR T-cell therapy, the SD rate was 64% with a median duration of SD of 56 days (range, 44-134).
“This study has shown the initial safety of intraventricular administration of HER2[-directed] CAR T cells alone and with LD,” lead study author Jana Portnow, MD, said in a presentation of the data. “[The addition of] LD did not increase the durability of SD, and we saw an increase in toxicity when LD was added. However, we also saw some evidence of on-target activity when LD was added.”
Portnow is a professor in the Department of Medical Oncology & Therapeutics Research and the co-director of the Brain Tumor Program at City of Hope in Duarte, California.
Investigators of the single-center study conducted at City of Hope enrolled patients at least 18 years of age with histologically confirmed HER2-positive breast cancer (defined as immunohistochemistry 3+ or gene amplification per fluorescence in situ hybridization) who had recurrent brain metastases after radiation or recurrent leptomeningeal metastases after intrathecal chemotherapy.1,2 Patients needed to have a Karnofsky performance status of at least 70, and there was no limit on the number of prior therapies.1 Patients were not allowed to be receiving dexamethasone at a dose higher than 6 mg per day, and patients also needed to stop systemic chemotherapy or endocrine therapy during the first 3 cycles of CAR T-cell therapy.
The HER2-directed CAR T-cell therapy was evaluated at 3 dose levels. Dose level 1 comprised 2 x 106 CAR T cells in cycle 1, 10 x 106 CAR T cells in cycle 2, and 10 x 106 CAR T cells in cycle 3 and beyond. At dose level 2, doses were 10 x 106 CAR T cells in cycle 1, 50 x 106 CAR T cells in cycle 2, and 50 x 106 CAR T cells in cycle 3 and beyond. At dose level 3, these respective doses were 20 x 106 CAR T cells, 100 x 106 CAR T cells, and 100 x 106 CAR T cells.
In the LD plus CAR T-cell therapy cohort, LD comprised cyclophosphamide at 300 mg/m2 per day and fludarabine at 25 mg/m2 per day, with each given for 3 days.
The safety of the CAR T-cell therapy, with or without LD, served as the trial’s primary end point. Secondary end points included the persistence of CAR T cells in cerebrospinal fluid (CSF) and peripheral blood; evidence of activation of the endogenous immune system; changes in cytokine levels in the CSF and peripheral blood; and central nervous system (CNS) clinical benefit, median CNS progression-free survival, and overall survival.
In the cohort of patients who received CAR T-cell therapy alone (n = 10), the median age was 49 years (range, 31-59), and 3 of these patients had leptomeningeal metastases. Patients in this cohort received a median of 6 doses of CAR T-cell therapy (range, 3-11), and they had received a median of 6 prior chemotherapies (range, 1-9). In the LD plus CAR T-cell therapy cohort (n = 13), the median age was 54 years (range, 34-76), and 6 patients had leptomeningeal metastases. Patients received a median of 5 doses of CAR T-cell therapy (range, 2-11), and these patients had received a median of 4 prior chemotherapies (range, 2-9).
Portnow also explained that a correlative study showed modest increases in persistence of HER2 CAR T cells in the CSF with escalating doses and the addition of LD.
In a case study of the first patient to receive LD prior to CAR T-cell therapy, which involved a 54-year-old woman with HER2-positive, hormone receptor–positive breast cancer involving brain and leptomeningeal metastases only, investigators detected an increase in CAR T-cell persistence after LD. Prior to this patient’s first dose of CAR T-cell therapy, she had the presence of large, highly atypical cells that were consistent with metastatic carcinoma. After the third dose, rare large atypical cells were present, suspicious for metastatic carcinoma. After the fourth and fifth doses of CAR T-cell therapy, no malignant cells were detected on CSF cytology.
The correlative studies also revealed that the HER2-directed CAR T cells led to an increase in proinflammatory cytokines in the CSF. However, these pro-inflammatory cytokines decreased over time, and an increase in anti-inflammatory cytokines was reported.
Disclosures: Portnow did not report any conflicts of interest.

If you’re not familiar with the adorable Astro Bot yet, there’s someone we’d like you to meet. The star of a PlayStation VR minigame and the PS5 pack-in has finally got his own full-length, non-VR adventure (although Rescue Mission is well…

Two University of Alabama at Birmingham football players were injured in an “incident” involving a third player Saturday morning, the school said.
The third student, described by UAB as a “suspect,” is in custody as the investigation continues….