A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G / GEJ) (Morpheus-Gastric Cancer)

Status: Active

Description

A Phase Ib / II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic G / GEJ cancer (hereafter referred to as gastric cancer). Two cohorts will be enrolled in parallel in this study: the second-line (2L) Cohort will consist of patients with gastric cancer who have progressed after receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the first-line setting, and the first-line (1L) Cohort will consist of patients with gastric cancer who have not received prior chemotherapy in this setting. In each cohort, eligible patients will be assigned to one of several treatment arms.

Eligibility Criteria

Inclusion Criteria

  • Age >/= 18 years;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  • Life expectancy >/= 3 months, as determined by the investigator;
  • Histologically or cytologically confirmed locally advanced unresectable or metastatic adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for the 2L Cohort: disease progression during or following a first-line platinum-containing or fluoropyrimidine-containing chemotherapy regimen);
  • Only for the 1L Cohort: human epidermal growth factor receptor 2 (HER2)-negative tumors;
  • Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1);
  • Adequate hematologic and end organ function based on laboratory results obtained within 14 days prior to initiation of study treatment;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm;
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm. Exclusion Criteria: Exclusion criteria for the 2L Cohort:
  • Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2000 mg;
  • Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of study treatment;
  • History of gastrointestinal perforation and/or fistulae within 6 months prior to initiation of study treatment;
  • Presence of a bowel obstruction, history or presence of inflammatory enteropathy, or extensive intestinal resection, Crohn disease, ulcerative colitis, or chronic diarrhea;
  • Uncontrolled arterial hypertension >/= 150/ >/= 90 millimeter of mercury (mmHg) despite standard medical management;
  • Chronic therapy with non-steroidal anti-inflammatory agents or other anti-platelet agents.

Exclusion Criteria

  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy;
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;
  • History of leptomeningeal disease;
  • Active or history of autoimmune disease or immune deficiency;
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan;
  • Positive test for human immunodeficiency virus (HIV) at screening;
  • Active hepatitis B virus (HBV) or hepatitis C (HCV) infection;
  • Severe infection within 4 weeks prior to initiation of study treatment;
  • Significant cardiovascular disease;
  • Significant bleeding disorder;
  • Prior allogeneic stem cell or solid organ transplantation;
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study;
  • Treatment with anticoagulation with warfarin, low-molecular-weight heparin, or similar agents for therapeutic purposes;
  • History of malignancy other than gastric or gastroesophageal junction carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death;
  • Known allergy or hypersensitivity to any of the study drugs or their excipients.

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Temporarily closed to accrual
Name Not Available

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: Sarah Rosales
Phone: 310-794-7686
Email: srosales@mednet.ucla.edu
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Raluca Dana Agafitei
Phone: 323-865-0467
Email: agafitei@med.usc.edu

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Hoffmann-La Roche

Trial IDs

Primary ID YO39609
Secondary IDs NCI-2017-01876, 2016-004529-17
Clinicaltrials.gov ID NCT03281369