Delving into the Latest Updates on Kaplan Hospital with Synapse

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Author: Martinez-Bueno, Alejandro ; Evron, Ella ; García-Sáenz, Jose A. ; Bischof, Georg Friedrich ; de Miguel, Maria J. ; Quinn, David I. ; Reid, Sonya A. ; Unni, Nisha ; Brufsky, Adam ; Saura, Cristina ; Solit, David B. ; Eli, Lisa DeFazio ; Hurvitz, Sara A. ; Bebchuk, Judith D. ; Mahalingam, Devalingam ; Wildiers, Hans ; Jhaveri, Komal L. ; De La Fouchardiere, Christelle ; Guerrero, Angel ; Bose, Ron

1094 Background: Genomic analyses of the SUMMIT metastatic breast cancer (mBC) cohorts suggested that resistance to neratinib (N) occurred primarily via acquisition of additional HER2alterations [Smyth et al. Cancer Discovery 2020]; this finding was independently confirmed in the MutHER clinical trial [Ma et al. Clin Cancer Res 2022]. Addition of trastuzumab (T) to N + fulvestrant (F) in HR+, HER2-negative, HER2-mutant mBC revealed increased efficacy compared to N+F [Jhaveri et al. Ann Oncol 2023]. Here, we report final data from SUMMIT evaluating whether the addition of T to N could improve outcomes in patients (pts) with HER2-mutant, triple-negative mBC (representing up to 3% of triple-negative mBCs) and performed next-generation sequencing (NGS) of serial biopsies to evaluate mechanisms of sensitivity and resistance. Methods: Pts with HER2-mutant triple-negative mBC received N (original SUMMIT cohort) or N+T (in the subsequent cohort): oral N 240 mg/d, i.v. T 8 mg/kg initially followed by 6 mg/kg q3w. Loperamide prophylaxis was mandatory during the first two cycles. Efficacy endpoints: confirmed objective response rate and clinical benefit rate (RECIST v1.1 or modified PERCIST); duration of response; progression-free survival. Retrospective central NGS was performed by MSK-IMPACT (tissue) or MSK-ACCESS (plasma). Results: 10 and 17 pts with triple-negative mBC were enrolled in the N and the N+T cohorts, respectively. Median no. of prior systemic regimens for metastatic disease was 2.5 (range 0–6) for the N and 2 (range 0–7) for the N+T cohort. Efficacy findings are summarized (Table). Diarrhea was the most commonly reported adverse event (N 80% any grade; 20% grade 3; N+T 100% any grade; 18% grade 3; no grade 4/5 or permanent discontinuations in either cohort). Correlation of efficacy to central NGS analysis is ongoing and will be reported. Conclusions: Treatment with either N and/or N+T yielded promising clinical efficacy and has been included in recent NCCN guidelines for HER2-mutant, triple-negative mBC. Molecular mechanisms of intrinsic or acquired sensitivity/resistance per genomic analysis will be reported. Clinical trial information: NCT01953926 . [Table: see text]

15 May 2000·BloodQ1 · MEDICINE

β2 Microglobulin-deficient (B2mnull) NOD/SCID mice are excellent recipients for studying human stem cell function

Q1 · MEDICINE

Article

Author: Kollet, Orit ; Greiner, Dale ; Peled, Amnon ; Byk, Tamara ; Lapidot, Tsvee ; Shultz, Leonard ; Ben-Hur, Herzl

AbstractHuman SCID repopulating cells (SRC) are defined based on their functional ability to repopulate the bone marrow of NOD/SCID mice with both myeloid and lymphoid cell populations. The frequency of SRC in umbilical cord blood cells is 1 in 9.3 × 105mononuclear cells. We report that as few as 8 × 104 human cord blood mononuclear cells transplanted into NOD/SCID/B2mnull mice resulted in mutlilineage differentiation in the murine bone marrow, revealing a more than 11-fold higher SRC frequency than in NOD/SCID mice. Moreover, as few as 2 to 5 × 103 CD34+ cells recovered from the bone marrow of primary transplanted NOD/SCID mice were sufficient for engrafting secondary NOD/SCID/B2mnull mice with SRC, suggesting SRC self-renewal. Thus, by using NOD/SCID/B2mnull mice as recipients, we established a functional assay for human stem cells capable of engrafting the bone marrow of primary and secondary transplanted immune-deficient mice with SRC, providing a model that better resembles autologous stem cell transplantation.

01 Dec 1999·Emerging Infectious DiseasesQ2 · MEDICINE

Serologic Evidence of Human Monocytic and Granulocytic Ehrlichiosis in Israel

Q2 · MEDICINE

ArticleOA

Author: Potasman, Israel ; Sthoeger, Zev ; Strenger, Carmella ; Waner, Trevor ; Amram, Lili ; Jacob, Amir ; Dawson, Jacqueline E. ; Keysary, Avi ; Keren, Gershon

We conducted a retrospective serosurvey of 1,000 persons in Israel who had fever of undetermined cause to look for Ehrlichia chaffeensis antibodies. Four of five cases with antibodies reactive to E. chaffeensis were diagnosed in the summer, when ticks are more active. All patients had influenzalike symptoms with high fever. None of the cases was fatal. Three serum samples were also seroreactive for antibodies to E. canis, and one was also reactive to the human granulocytic ehrlichiosis (HGE) agent. The titer to the HGE agent in this patient was higher than the serum titer to E. chaffeensis, and the Western blot analysis also indicated that the HGE agent was the primary cause of infection. We present the first serologic evidence that the agents of human monocytic ehrlichiosis (HME) and HGE are present in Israel. Therefore, human ehrlichiosis should be included in the differential diagnoses for persons in Israel who have been exposed to ticks and have influenzalike symptoms.

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