Back to resultsA Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)
Primary Purpose
Colorectal Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Regorafenib
Atezolizumab
Imprime PGG
Bevacizumab
Isatuximab
Selicrelumab
Idasanutlin
AB928
LOAd703
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
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
- Presence of BRAFV600E mutation
- 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
- Inability to swallow medications
- Malabsorption condition that would alter the absorption of orally administered medications
- Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
- Urine dipstick ≥ 2+ protein or ≥ 3.5 g of protein in a 24-hour urine collection
Sites / Locations
- City of Hope Comprehensive Cancer Center
- Yale University
- Dana Farber Cancer Institute
- Washington University School of Medicine
- Columbia University Medical Center
- Memorial Sloan-Kettering Cancer Center
- Peter MacCallum Cancer Center
- Centre Georges François Leclerc; Pharmacie des Essais Cliniques
- Centre Leon Berard
- Institut Claudius Regaud; Departement Oncologie Medicale
- Institut Gustave Roussy
- Seoul National University Hospital
- Samsung Medical Center
- Asan Medical Center.
- CHUV; Departement d'Oncologie
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Regorafenib (Control)
Atezolizumab + Imprime PGG + Bevacizumab
Atezolizumab + Isatuximab
Atezolizumab + Selicrelumab + Bevacizumab
Atezolizumab + Idasanutlin
Atezolizumab + Regorafenib
Atezolizumab + Regorafenib + AB928
Atezolizumab + LOAd703
Arm Description
Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Outcomes
Primary Outcome Measures
Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Secondary Outcome Measures
Progression Free Survival (PFS) as Determined by Investigator According to RECIST v1.1
Overall Survival (OS)
Percentage of Participants Who Are Alive at Landmark Timepoints
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
Disease Control Rate (DCR), as Determined by the Investigator per RECIST v1.1
Percentage of Participants with Adverse Events (AEs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03555149
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
The Sponsor made the decision to terminate the study due to start up and recruitment issues caused by limited resource availability at the treating centers.
Study Start Date
September 27, 2018 (Actual)
Primary Completion Date
September 26, 2022 (Actual)
Study Completion Date
September 26, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Regorafenib (Control)
Arm Type
Active Comparator
Arm Description
Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Arm Title
Atezolizumab + Imprime PGG + Bevacizumab
Arm Type
Experimental
Arm Description
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Arm Title
Atezolizumab + Isatuximab
Arm Type
Experimental
Arm Description
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Arm Title
Atezolizumab + Selicrelumab + Bevacizumab
Arm Type
Experimental
Arm Description
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Arm Title
Atezolizumab + Idasanutlin
Arm Type
Experimental
Arm Description
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Arm Title
Atezolizumab + Regorafenib
Arm Type
Experimental
Arm Description
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Arm Title
Atezolizumab + Regorafenib + AB928
Arm Type
Experimental
Arm Description
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Arm Title
Atezolizumab + LOAd703
Arm Type
Experimental
Arm Description
Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.
Intervention Type
Drug
Intervention Name(s)
Regorafenib
Intervention Description
Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
Atezolizumab will be administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of 21-day cycles, with the exception of the Atezolizumab + Selicrelumab + Bevacizumab, Atezolizumab + Idasanutlin, Atezolizumab + Regorafenib and Atezolizumab + Regorafenib + AB928 arms where the Atezolizumab will be administered by IV infusion every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Imprime PGG
Intervention Description
Imprime PGG will be administered by IV infusion weekly on Days 1, 8, and 15 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab will be administered by IV infusion on Day 1 of each 21-day cycle for the Atezolizumab + Imprime PGG + Bevacizumab arm, and on Day 1 and Day 15 of each 28-day cycle for the Atezolizumab + Selicrelumab + Bevacizumab arm.
Intervention Type
Drug
Intervention Name(s)
Isatuximab
Intervention Description
Isatuximab will be administered on Day 1, 8 and 15 of cycle 1 and on day 1 of all subsequent cycles. Cycles will be 21 days long.
Intervention Type
Drug
Intervention Name(s)
Selicrelumab
Intervention Description
Selicrelumab will be administered by subcutaneous (SC) injection on Day 1 of cycles 1-4 and every third cycle thereafter. Cycles will be 28 days long.
Intervention Type
Drug
Intervention Name(s)
Idasanutlin
Intervention Description
Idasanutlin will be administered orally on Days 1-5 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
AB928
Intervention Description
AB928 will be administered orally once daily on Days 1-28 of each 28-day cycle.
Intervention Type
Genetic
Intervention Name(s)
LOAd703
Other Intervention Name(s)
Delolimogene mupadenorepvec
Intervention Description
LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.
Primary Outcome Measure Information:
Title
Best Confirmed Overall Response Rate (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)
Secondary Outcome Measure Information:
Title
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)
Title
Overall Survival (OS)
Time Frame
From randomization up to death from any cause (up to approximately 3-5 years)
Title
Percentage of Participants Who Are Alive at Landmark Timepoints
Time Frame
3, 6, 12, and 18 months
Title
Duration of Response (DOR) as Determined by the Investigator According 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)
Title
Disease Control Rate (DCR), 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)
Title
Percentage of Participants with Adverse Events (AEs)
Time Frame
From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 3-5 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Presence of BRAFV600E mutation
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
Inability to swallow medications
Malabsorption condition that would alter the absorption of orally administered medications
Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
Urine dipstick ≥ 2+ protein or ≥ 3.5 g of protein in a 24-hour urine collection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Peter MacCallum Cancer Center
City
North Melbourne
State/Province
Victoria
ZIP/Postal Code
3051
Country
Australia
Facility Name
Centre Georges François Leclerc; Pharmacie des Essais Cliniques
City
Dijon Cedex
ZIP/Postal Code
21079
Country
France
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Institut Claudius Regaud; Departement Oncologie Medicale
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Asan Medical Center.
City
Seoul
ZIP/Postal Code
5505
Country
Korea, Republic of
Facility Name
CHUV; Departement d'Oncologie
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
12. IPD Sharing Statement
Learn more about this trial
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)
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