A5026959613- Cancer therapeutics and mechanisms
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Drug Transport and Resistance Mechanisms
- PARP inhibition in cancer therapy
- HER2/EGFR in Cancer Research
- Prostate Cancer Treatment and Research
- Cancer Treatment and Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Chemical Synthesis and Analysis
- Lung Cancer Research Studies
- Cancer, Hypoxia, and Metabolism
- Amino Acid Enzymes and Metabolism
- Liver Disease Diagnosis and Treatment
- Computational Drug Discovery Methods
- Neuroendocrine Tumor Research Advances
- Multiple Myeloma Research and Treatments
- Hepatocellular Carcinoma Treatment and Prognosis
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Pharmacogenetics and Drug Metabolism
- Click Chemistry and Applications
- Lanthanide and Transition Metal Complexes
- Drug-Induced Hepatotoxicity and Protection
Sanofi (France)
2013-2023
Hôpital Européen Georges-Pompidou
2017
Institut Gustave Roussy
2017
Herlev Hospital
2017
Institut Claudius Regaud
2017
Sidney Kimmel Comprehensive Cancer Center
2017
Université Paris-Sud
2017
Copenhagen University Hospital
2017
Cancer Center of Kansas
2012
Huntsman (United States)
2012
Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA ( ClinicalTrials.gov identifier: NCT01308567) assessed whether 20 mg/m2 (C20) or 25 (C25) superior to 75 (D75) in terms of OS chemotherapy-naïve mCRPC. Patients and Methods mCRPC Eastern Cooperative Oncology Group performance status 0 2 were randomly assigned 1:1:1 receive C20, C25, D75...
Purpose Cabazitaxel 25 mg/m2 (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) the phase III TROPIC study. The PROSELICA study ClinicalTrials.gov identifier: NCT01308580) assessed noninferiority of cabazitaxel 20 (C20) C25 mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability disease per Response Evaluation Criteria...
Noninvasive biomarkers are needed to guide metastatic castration-resistant prostate cancer (mCRPC) treatment. To clinically qualify baseline and on-treatment cell-free DNA (cfDNA) concentrations as of patient outcome following taxane chemotherapy. Blood for cfDNA analyses was prospectively collected from 571 mCRPC patients participating in two phase III clinical trials, FIRSTANA (NCT01308567) PROSELICA (NCT01308580). Patients received docetaxel (75 mg/m2) or cabazitaxel (20 25 first-line...
Better blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and circulating tumour (ctDNA). Low-pass whole-genome sequencing (lpWGS) ctDNA can provide information on mCRPC behaviour. To validate clinically qualify plasma lpWGS for mCRPC. data were obtained patients consenting optional substudies two prospective phase 3 trials (FIRSTANA PROSELICA). In...
5006 Background: The Phase III TROPIC study (NCT00417079) reported significant improvement in overall survival (OS) for cabazitaxel 25 mg/m2IV Q3W plus prednisone 10 mg PO QD (P) vs. mitoxantrone P mCRPC pts previously treated with a docetaxel (D)-containing regimen. FIRSTANA examined if 20 mg/m² (C20) or (C25) IV is superior to 75 (D75) terms of OS CN pts. Methods: In this multinational, open label phase study, pts, ECOG PS 0-2, who had progressed after castration were randomized 1:1:1 C20,...
9039 Background: Tusamitamab ravtansine (tusa) is a novel antibody-drug conjugate that selectively targets CEACAM5, cell surface glycoprotein highly expressed in several tumor types. In previously reported results from an open-label Phase 1/2 study (NCT02187848), tusa showed promising antitumor activity patients (pts) with heavily pretreated NSQ NSCLC and high CEACAM5 expression (Gazzah A et al. J Clin Oncol. 2020;38[15 suppl]:9505). Herein we report for pts treated ≥ 12 mo or moderate...
5008 Background: The Phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for C plus prednisone (P) (25 mg/m2once every 3 weeks 10 mg orally once daily) versus mitoxantrone P (Hazard Ratio [HR] 0.70; < 0.0001) pts with mCRPC previously treated D. This PROSELICA (NCT01308580) was designed to determine the relative efficacy and safety profile of C20 compared C25 P. Methods: In this randomized, open-label, multinational phase study, ECOG performance...
9505 Background: We report updated safety and efficacy of DM4-conjugated anti-CEACAM5 ADC from the expansion part first-in-human study (NCT02187848; Gazzah A et al. J Clin Oncol. 2019;37:15, 9072) in 92 NSQ NSCLC pts. Methods: CEACAM5 expression was assessed by immunohistochemistry on archived tumor samples. Two cohorts pts have been analyzed: moderate high expressors, with at ≥2+ intensity between ≥1% to < 50% ≥50% cell population, respectively. SAR408701 administered 100 mg/m 2 IV every...
In imaging-based clinical trials, it is common practice to perform double reads for each image, discrepant interpretations can result from these two different evaluations. this study we analyzed discrepancies that occurred between local investigators (LI) and blinded independent central review (BICR) by comparing reader-selected imaging scans lesions. Our goal was identify the causes of declarations progressive disease (PD) LI BICR in a trial. We retrospectively data RECIST 1.1-based,...
Abstract Tusamitamab ravtansine (SAR408701) is an antibody-drug conjugate (ADC), combining a humanized monoclonal antibody (IgG1) targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and potent cytotoxic maytansinoid derivative, DM4, inhibiting microtubule assembly. SAR408701 currently in clinical development for the treatment of advanced solid tumors expressing CEACAM5. It administered intravenously as conjugated with average Drug Antibody Ratio (DAR) 3.8. During...
CEACAM5 is a cell-surface glycoprotein expressed on epithelial cells of some solid tumors. Tusamitamab ravtansine (SAR408701), humanized antibody-drug conjugate targeting CEACAM5, in clinical development for nonsquamous non-small cell lung cancer (NSQ-NSCLC) with high expression (HE), defined as membranous immunohistochemistry staining at ≥ 2+ intensity 50% tumor cells.We investigated correlations between by immunohistochemistry, protein ELISA, and RNA RNA-seq NSQ-NSCLC patient-derived...
TPS9625 Background: Despite recent advances in the treatment of NSQ NSCLC, including integration immune checkpoint inhibitors (ICI) into first-line all patients, novel therapies are necessary at disease progression. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), a cell-surface glycoprotein, is overexpressed several tumor types, NSCLC; ~20% patients express high CEACAM5 levels. SAR408701 an ADC combining humanized antibody targeting with potent cytotoxic maytansinoid...
Tusamitamab ravtansine is an antibody-drug conjugate that targets carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and delivers a cytotoxic maytansinoid payload. In phase I dose-escalation study, the maximum tolerated dose (MTD) was 100 mg/m2 every 2 weeks (Q2W). Here we report results for two alternative schedules.Adults ages ≥18 years (range, 34-73) with locally advanced/metastatic solid tumors (N = 43; colon/rectum, 29; stomach, 7; pancreas, 4; other, 3)...
TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m 2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) P (MP) (median OS 15.1 12.7 mos; HR 0.70; < 0.0001) pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities treatment of that has progressed after Cbz toxicity...
5014 Background: Biomarkers are needed to guide CRPC treatment; we evaluated [cfDNA] pre- and post-TT, associating this with outcome. Methods: cfDNA was isolated quantified from 1 mL of plasma, prospectively collected patients (PTS) recruited two phase III trials, utilizing QIAamp Circulating Nucleic Acid Quant-IT Picogreen HS DNA kits. FIRSTANA (NCT01308567) compared docetaxel (D; 75mg/m2) cabazitaxel (C; 20 or 25mg/m2) as 1st line TT; PROSELICA (NCT01308580) C at 25 mg/m2 2nd TT. Results:...
15001 Background: BIBF1120 is a triple angiokinase inhibitor (VEGFR1–3, PDGFR and FGFR). BIBW2992 an of EGFR HER2. Combined blockade these targets may have additive or synergistic effects on tumour response. Methods: was administered orally twice daily at 250 mg days 1 to 7, followed by 50 once 8–14. Sequential administration repeated in 4 weeks (wks) cycles for least 24 wks. Patients (pts) were eligible treatment courses the absence progression disease (PD). Objective response rate (OR)...
TPS5099 Background: Cbz 25 mg/m 2 IV Q3W + P 10 mg PO QD has an established safety profile and significantly improves overall survival (OS) vs mitoxantrone in pts with mCRPC previously treated a D-containing regimen (phase III TROPIC study; NCT00417079; median OS: 15.1 12.7 mos; HR: 0.70; < 0.0001). Pooled data on file suggest that lower Grade 3–4 neutropenia rates are observed ≥ (61% 74%). In attempt to further improve the therapeutic index of second-line treatment mCRPC, PROSELICA...
e15115 Background: Cabazitaxel (Cbz) improves overall survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure, compared mitoxantrone (HR 0.70; 95% CI 0.59–0.83; p<0.0001). Following Cbz approval for the treatment of mCRPC, this study was undertaken to evaluate any effect on QTc interval. Methods: This prospective, multinational, open-label (NCT01087021) enrolled pts advanced solid tumors (without other therapeutic options). 25 mg/m²...
9072 Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a cell-surface glycoprotein highly expressed in several tumor types. This Phase 1, open-label, dose-escalation, dose-expansion study (NCT02187848) investigated SAR408701, DM4 conjugated ADC targeting CEACAM5, pts with advanced solid tumors. During dose escalation, maximum tolerated (MTD) of SAR408701 was 100 mg/m 2 IV once every weeks 14-day cycles. Interim analysis an ongoing expansion cohort NSQ NSCLC...
e15003 Background: Tusamitamab ravtansine (tusa rav) is a novel antibody-drug conjugate (ADC) targeted to carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and delivering DM4, cytotoxic maytansinoid. CEACAM5 highly expressed in several tumor types, including nonsquamous non-small lung cancer (NSQ NSCLC). An open-label, Phase 1/2, dose-escalation/expansion study (NCT02187848) patients with advanced solid tumors found the maximum tolerated dose of tusa rav be 100 mg/m 2 every...