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

NCT03555149

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) who experienced disease progression during or following two lines of treatment. Eligible patients will be assigned to one of several treatment arms.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)
  • Official Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Colorectal Cancer (Morpheus-CRC)

Clinical Trial IDs

  • ORG STUDY ID: CO39612
  • SECONDARY ID: 2017-004566-99
  • NCT ID: NCT03555149

Conditions

  • Colorectal Cancer

Interventions

DrugSynonymsArms
RegorafenibRegorafenib (Control)
AtezolizumabAtezolizumab + Imprime PGG + Bevacizumab
Imprime PGGAtezolizumab + Imprime PGG + Bevacizumab
BevacizumabAtezolizumab + Imprime PGG + Bevacizumab
IsatuximabAtezolizumab + Isatuximab

Purpose

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) who experienced disease progression during or following two lines of treatment. Eligible patients will be assigned to one of several treatment arms.

Trial Arms

NameTypeDescriptionInterventions
Regorafenib (Control)Active ComparatorParticipants will continue to receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria
  • Regorafenib
Atezolizumab + Imprime PGG + BevacizumabExperimentalParticipants will continue to receive treatment until unacceptable toxicity or disease progression per RECIST V1.1. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
  • Atezolizumab
  • Imprime PGG
  • Bevacizumab
Atezolizumab + IsatuximabExperimentalParticipants will continue to receive treatment until unacceptable toxicity or disease progression per RECIST V1.1. Participants who progress on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria
  • Atezolizumab
  • Isatuximab

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Life expectancy ≥ 3 months, as determined by the investigator

          -  Disease progression during or following two separate lines of treatment for metastatic
             colorectal cancer (mCRC) that consisted of fluoropyrimidine-, oxaliplatin-, or
             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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Objective Response (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame:From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) as Determined by Investigator According to RECIST v1.1
Time Frame:From randomization up to the first occurrence of disease or death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Overall Survival (OS) After Randomization
Time Frame:From randomization up to death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of Participants Who Are Alive at Month 6
Time Frame:Month 6
Safety Issue:
Description:
Measure:Duration of Response (DOR) as Deteremined by the Investigator Accordnig to RECIST v1.1
Time Frame:From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of Participants With Disease Control, as Determined by the Investigator per RECIST v1.1
Time Frame:From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days after last dose (up to approximately 3-5 years
Safety Issue:
Description:
Measure:Percentage of Participants with ADAs to Bevacizumab
Time Frame:Predose (0 h) on Day 1 of Cycles 1, 3 (cycle = 21 days); 30 days after last dose (approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of Participants with ADAs to Isatuximab
Time Frame:Predose (0 h) on Day 1 of Cycles 1, 2, 3 (expansion phase only), 4, 6, 8, 10, 12, 16 (cycle = 21 days); 30 days after last dose (approximately 3-5 years)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab
Time Frame:Pre-infusion (0 hour [hr]), Post infusion (30 minutes (min)) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 4, 8, 12, 16 (each cycle=21 days); 30 days after last dose (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Serum Concentration of Bevacizumab
Time Frame:Pre-infusion (0 hour [hr]) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 3 (each cycle=21 days); 30 days after last dose (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Serum Concentration of Imprime PGG
Time Frame:Pre-infusion (0 hour [hr]), Post infusion (10 minutes (min)) on Day 1 and 15 of Cycle 1 (cycle=21 days)
Safety Issue:
Description:
Measure:Plasma Concentration of Isatuximab
Time Frame:Pre-infusion (0 hour [hr]), Post infusion (30 minutes (min)) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 4, 8, 12, 16 (each cycle=21 days); 30 days after last dose (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Plasma Concentration of Cobimetinib
Time Frame:Pre-infusion (0 hour [hr]), Post infusion (2 to 4 hours) on Day 15 of Cycle 1 (cycle=21 days)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

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