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OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors.
Gutierrez, Martin; Moreno, Victor; Heinhuis, Kimberley M; Olszanski, Anthony J; Spreafico, Anna; Ong, Michael; Chu, Quincy; Carvajal, Richard D; Trigo, José; Ochoa de Olza, Maria; Provencio, Mariano; De Vos, Filip Yves; De Braud, Filippo; Leong, Stephen; Lathers, Deanne; Wang, Rui; Ravindran, Palani; Feng, Yan; Aanur, Praveen; Melero, Ignacio.
Afiliación
  • Gutierrez M; John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey. martin.gutierrez@hackensackmeridian.org.
  • Moreno V; START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
  • Heinhuis KM; The Netherlands Cancer Institute, Antoni Van Leeuwenhoek, Amsterdam, the Netherlands.
  • Olszanski AJ; Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • Spreafico A; Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Ong M; The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
  • Chu Q; Cross Cancer Institute, Edmonton, Alberta, Canada.
  • Carvajal RD; Columbia University Irving Medical Center, New York, New York.
  • Trigo J; Hospital Universitario Regional y Virgen de la Victoria, IBIMA, Málaga, Spain.
  • Ochoa de Olza M; Vall d'Hebron University Hospital, Barcelona, Spain.
  • Provencio M; Hospital Universitario Puerta de Hierro, Majadahonda, Spain.
  • De Vos FY; University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • De Braud F; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Leong S; University of Colorado Cancer Center, Aurora, Colorado.
  • Lathers D; Bristol Myers Squibb, Princeton, New Jersey.
  • Wang R; Bristol Myers Squibb, Princeton, New Jersey.
  • Ravindran P; Bristol Myers Squibb, Princeton, New Jersey.
  • Feng Y; Bristol Myers Squibb, Princeton, New Jersey.
  • Aanur P; Bristol Myers Squibb, Princeton, New Jersey.
  • Melero I; Clínica Universidad De Navarra, Pamplona, Spain. *was an employee of Bristol Myers Squibb at the time the studies were performed.
Clin Cancer Res ; 27(2): 460-472, 2021 01 15.
Article en En | MEDLINE | ID: mdl-33148673
ABSTRACT

PURPOSE:

This phase I/IIa study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist IgG1 mAb, ± nivolumab and/or ipilimumab in patients with advanced solid tumors. PATIENTS AND

METHODS:

Patients (with non-small cell lung, renal cell, bladder, other advanced cancers) received BMS-986178 (20-320 mg) ± nivolumab (240-480 mg) and/or ipilimumab (1-3 mg/kg). The primary endpoint was safety. Additional endpoints included immunogenicity, pharmacodynamics, pharmacokinetics, and antitumor activity per RECIST version 1.1.

RESULTS:

Twenty patients received BMS-986178 monotherapy, and 145 received combination therapy in various regimens (including two patients receiving nivolumab monotherapy). With a follow-up of 1.1 to 103.6 weeks, the most common (≥5%) treatment-related adverse events (TRAEs) included fatigue, pruritus, rash, pyrexia, diarrhea, and infusion-related reactions. Overall, grade 3-4 TRAEs occurred in one of 20 patients (5%) receiving BMS-986178 monotherapy, six of 79 (8%) receiving BMS-986178 plus nivolumab, zero of two receiving nivolumab monotherapy, six of 41 (15%) receiving BMS-986178 plus ipilimumab, and three of 23 (13%) receiving BMS-986178 plus nivolumab plus ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy, and the MTD was not reached in either the monotherapy or the combination escalation cohorts. No objective responses were seen with BMS-986178 alone; objective response rates ranged from 0% to 13% across combination therapy cohorts.

CONCLUSIONS:

In this study, BMS-986178 ± nivolumab and/or ipilimumab appeared to have a manageable safety profile, but no clear efficacy signal was observed above that expected for nivolumab and/or ipilimumab.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Receptores OX40 / Anticuerpos Monoclonales / Neoplasias Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Receptores OX40 / Anticuerpos Monoclonales / Neoplasias Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article