4 results on '"Melissa Mathias"'
Search Results
2. Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing
- Author
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Thomas Eigentler, Danny Rischin, Michael R Migden, Annette M Lim, Chrysalyne D Schmults, Nikhil I Khushalani, Lara A Dunn, Leonel Hernandez-Aya, Anne Lynn S Chang, Badri Modi, Claas Ulrich, Brian Stein, Jessica L Geiger, Emmanuel Okoye, Melissa Mathias, Jocelyn Booth, Siyu Li, and Matthew G Fury
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).Methods The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.Results For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).Conclusion In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration number Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498
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- 2020
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3. 535 A phase I/II study of REGN7075 (EGFRxCD28 costimulatory bispecific antibody) in combination with cemiplimab (anti–PD-1) in patients with advanced solid tumors
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Melissa Lynne Johnson, Frank Seebach, Dimitris Skokos, Roman Groisberg, Israel Lowy, Kerry Casey, Melissa Mathias, Siyu Li, Matthew G. Fury, Hyunsil Han, and Nehal Lakhani
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Pharmacology ,Cancer Research ,Bispecific antibody ,Chemistry ,Immunology ,Anti pd 1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Phase i ii ,Oncology ,Cancer research ,Molecular Medicine ,Immunology and Allergy ,In patient ,RC254-282 - Abstract
BackgroundT-cell redirecting bispecific antibodies (bsAbs) are therapeutics that recognize two distinct antigens: a tumor-associated antigen on tumor cells to promote recruitment of T-cells to the tumor, and a receptor on T-cells to potentiate anti-tumor activity. REGN7075 is a human immunoglobulin G4-based costimulatory bsAb designed to bridge epidermal growth factor receptor (EGFR) positive tumor cells with CD28 positive T-cells and to provide amplified T-cell receptor-CD3 complex-mediated T-cell activation within the tumor, through the activation of CD28 co-stimulation. In genetically humanized immunocompetent mouse models, REGN7075 in combination with anti–PD-1 (antibody directed against programmed cell death-1 receptor) improved anti-tumor activity compared with either single agent alone.1MethodsThis is an open label, Phase I/II, first-in-human study evaluating the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of REGN7075 (EGFRxCD28) alone and in combination with cemiplimab in patients with advanced solid tumors (NCT04626635). Patients must have a protocol-defined advanced solid tumor, be ≥18 years of age (≥20 years in Japan), have an Eastern Cooperative Oncology Group performance status of 0 or 1, and be naïve to anti–PD-1/anti–PD-ligand(L)1.This study includes dose escalation (a 4+3 design modified from 3+3; Part 1) and expansion phases (Part 2). In Part 1, patients will receive a lead-in of REGN7075 monotherapy for 3 weeks followed by combination therapy with cemiplimab 350 mg every 3 weeks. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or other stopping criterion is met. Once a recommended Phase 2 dose is determined in Part 1, four tumor-specific expansion cohorts will be opened: non-small cell lung cancer (PD-L1 ≥50%), triple-negative breast cancer, colorectal cancer (microsatellite stable), and cutaneous squamous cell carcinoma. Primary endpoints are safety and tolerability of REGN7075 alone or in combination with cemiplimab for Part 1, and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 for Part 2. This study is currently open to enrollment.Trial RegistrationClinicalTrials.gov identifier NCT04626635.ReferencesWaite JC, Wang B, Haber L, et al. Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. Sci Transl Med 2020;12:2325.Ethics ApprovalThis study was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The study protocol and all amendments were approved by the institutional review board/ethics committee at each participating study site.ConsentAll patients provided written informed consent.
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- 2021
4. Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing
- Author
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Michael R. Migden, Claas Ulrich, Annette M. Lim, Elizabeth Stankevich, Melissa Mathias, Chrysalyne D. Schmults, Israel Lowy, Brian Stein, Matthew G. Fury, Siyu Li, Dirk Schadendorf, Jessica L. Geiger, Leonel Hernandez-Aya, Thomas Eigentler, Axel Hauschild, Vladimir Jankovic, Jocelyn Booth, Ralf Gutzmer, Nikhil I. Khushalani, Anne Lynn S. Chang, Danny Rischin, Emmanuel Okoye, Anna C. Pavlick, Alexander Guminski, Murad Alam, Badri Modi, Brett G.M. Hughes, and Lara Dunn
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Skin Neoplasms ,Programmed Cell Death 1 Receptor ,Medizin ,Phases of clinical research ,Kaplan-Meier Estimate ,Gastroenterology ,0302 clinical medicine ,Immunology and Allergy ,Drug Dosage Calculations ,Infusions, Intravenous ,Immune Checkpoint Inhibitors ,RC254-282 ,Clinical/Translational Cancer Immunotherapy ,Aged, 80 and over ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Middle Aged ,Progression-Free Survival ,Diarrhea ,Oncology ,Tolerability ,030220 oncology & carcinogenesis ,Cohort ,Carcinoma, Squamous Cell ,Molecular Medicine ,Female ,immunotherapy ,medicine.symptom ,Adult ,medicine.medical_specialty ,Immunology ,Antibodies, Monoclonal, Humanized ,Drug Administration Schedule ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,In patient ,Dosing ,Adverse effect ,Aged ,Pharmacology ,Dose-Response Relationship, Drug ,business.industry ,Body Weight ,Cancer ,medicine.disease ,030104 developmental biology ,tumor biomarkers ,business ,Follow-Up Studies - Abstract
BackgroundCemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).MethodsThe primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.ResultsFor Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).ConclusionIn patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration numberClinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498
- Published
- 2020
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