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A Phase 1/2 Study of the Safety, Tolerability and Efficacy of Epacadostat Administered in Combination with Nivolumab in Select Advanced Cancers

Description

This is a Phase 1/2, open label study that will be conducted in 2 parts. The first part of the study (Phase 1) will consist of a dose-escalation assessment of the safety and tolerability of epacadostat administered with nivolumab in subjects with select advanced solid tumors and lymphomas including melanoma (MEL), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), head and neck squamous cell carcinoma (SCCHN), ovarian cancer, and B cell non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL). The second part (Phase 2) of the study will include expansion cohorts in the tumor types tested in Phase 1 (except diffuse large B-cell lymphoma (DLBCL) will be the only lymphoma permitted and Phase 2 will also include a cohort for glioblastoma) with a) historically good activity with nivolumab monotherapy, and b) with historically low activity with nivolumab monotherapy.

Phase

Phase 1/2 - for trials that are a combination of phases 1 and 2.

Inclusion and Exclusion Criteria

  • Male or female subjects, age 18 years or older
  • Subjects with histologically or cytologically confirmed NSCLC, MEL, CRC, SCCHN, ovarian cancer, recurrent B cell NHL or HL, or glioblastoma
  • Subjects with Stage IIIB, Stage IV, or recurrent NSCLC; unresectable or Stage IV MEL; recurrent (unresectable) or metastatic CRC; recurrent (unresectable) or metastatic SCCHN; FIGO Stage Ic, II, III, or IV recurrent ovarian cancer (unresectable) or relapsed or refractory B cell NHL (including relapsed or refractory DLBCL) or HL, or glioblastoma and meet the following tumor specific criteria:
  • Subjects with Stage IIIB, Stage IV, or recurrent NSCLC:
  • Prior systemic therapies must include a platinum-based regimen
  • All subjects must be screened for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) fusion oncogene status and if positive treated with a tyrosine kinase inhibitor
  • Malignancy must be deemed unresectable
  • Subjects with unresectable or Stage IV MEL:
  • Documentation of V600E-activating BRAF mutation status or consent to BRAF V600E mutation testing during the screening period
  • Subjects may be treatment-naïve or have received only 1 prior treatment for advanced or metastatic disease
  • Subjects with recurrent (unresectable) or metastatic CRC:
  • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
  • Prior treatment: Progression following last administration of approved standard therapies
  • Subjects with recurrent or metastatic SCCHN:
  • Metastatic or recurrent squamous cell carcinoma not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy) -Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx and salivary gland or non-squamous histologies will be excluded
  • Documentation of human papillomavirus status (eg, p16-status) of tumor
  • Subjects with International Federation of Gynecology and Obstetrics (FIGO) Stage Ic, Stage II, Stage III, Stage IV, recurrent, or persistent (unresectable) histologically confirmed epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube carcinoma:
  • Subjects must have received a platinum-taxane-based regimen as frontline therapy
  • Borderline, low malignant potential epithelial carcinoma per histopathology is excluded
  • Subjects with relapsed or recurrent B cell NHL or HL (including relapsed or refractory DLBCL excluding Burkitt's lymphoma and precursor B-lymphoblastic leukemia/lymphoma):
  • Prior allogeneic stem-cell transplantation is excluded
  • Not a candidate for curative therapy or hematopoietic stem cell transplantation (either due to disease burden, fitness or preference)
  • Subjects must have relapsed or have had refractory DLBCL specifically for Phase 2
  • Subjects with HL: must be brentuximab vedotin refractory or intolerant
  • Subjects with histologically confirmed diagnosis of glioblastoma
  • Previous first-line treatment with at least radiotherapy and temozolomide
  • Documented first recurrence of glioblastoma by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI) per RANO criteria
  • MRI within 14 days to start of study drug
  • An interval of at least 12 weeks after the end of prior radiation therapy
  • An interval of ≥21 days and full recovery from surgical resection prior to enrollment
  • Presence of measurable disease by RECIST v1.1 for solid tumors or Cheson criteria for B cell NHL (including DLBCL) or HL. For subjects with glioblastoma, presence of measurable disease is not required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  • Females of child-bearing potential and males who use adequate birth control, from screening through 125 days after the last dose of study treatment
  • Fresh baseline tumor biopsies (defined as a biopsy specimen taken since completion of the most recent prior chemotherapy regimen) are required for all cohorts except glioblastoma

  • Laboratory and medical history parameters not within Protocol-defined range unless directly resulting from the bone marrow infiltration of the underlying malignancy
  • Currently pregnancy or breastfeeding
  • Subjects who have received prior immune checkpoint inhibitors (eg, anti-CTLA-4, anti-PD-1, anti-PD-L1, and any other antibody or drug specifically targeting T-cell costimulation) or an IDO inhibitor. Subjects who have received experimental vaccines or other immune therapies should be discussed with the medical monitor to confirm eligibility o Anti-CTLA-4 given as first-line treatment for metastatic MEL will be permitted
  • Untreated central nervous system (CNS) metastases or CNS metastases that have progressed (eg, evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases)
  • Subjects with any active or inactive autoimmune process
  • Evidence of interstitial lung disease or active, noninfectious pneumonitis
  • Exclusion specific for subjects with unresectable or Stage IV MEL: Ocular MEL

Sites

Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.

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