A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)

Status: Active

Description

A phase Ib / II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (mCRC) that became refractory to first- and second-line standard therapies. Eligible patients will be assigned to one of several treatment arms.

Eligibility Criteria

Inclusion Criteria

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy ≥ 3 months, as determined by the investigator
  • Histologically confirmed adenocarcinoma originating from the colon or rectum
  • Metastatic disease not amenable to local treatment
  • Disease progression during or following not more than two separate lines of treatment for metastatic colorectal cancer (mCRC) that consisted of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy in combination with a biologic agent
  • Measurable disease (at least one target lesion) according to RECIST v1.1
  • Adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment

Exclusion Criteria

  • High microsatellite instability (MSI-H) tumor
  • Mutation in the BRAF oncogene
  • Prior treatment with any of the protocol-specified study treatments
  • Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Biologic treatment within 2 weeks prior to initiation of study treatment, or other systemic treatment for CRC within 2 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Eligibility only for the control arm
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
  • Current treatment with anti-viral therapy for HBV
  • Uncontrolled pleural effusion, pericardial effusion, ascites requiring recurrent drainage procedures (once monthly or more frequently), or tumor related-pain,
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN)
  • Symptomatic, untreated, or actively progressing CNS metastases
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • Active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Significant cardiovascular disease
  • Grade ≥3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment
  • 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
  • History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins

Locations & Contacts

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Name Not Available

Connecticut

New Haven
Yale University
Status: Approved
Contact: Kamil Sadowski
Phone: 203-785-6661
Email: kamil.sadowski@yale.edu

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Christian Hospital
Status: Active
Name Not Available
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

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

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Hoffmann-La Roche

Trial IDs

Primary ID CO39612
Secondary IDs NCI-2018-01814, 2017-004566-99
Clinicaltrials.gov ID NCT03555149