Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03555149
Recruitment Status : Recruiting
First Posted : June 13, 2018
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: Regorafenib Drug: Atezolizumab Drug: Imprime PGG Drug: Bevacizumab Drug: Isatuximab Drug: Selicrelumab Drug: Idasanutlin Drug: AB928 Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 326 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : May 23, 2021
Estimated Study Completion Date : February 3, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Regorafenib (Control)
Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Drug: Regorafenib
Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Experimental: Atezolizumab + Imprime PGG + Bevacizumab
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.
Drug: Atezolizumab
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.

Drug: Imprime PGG
Imprime PGG will be administered by IV infusion weekly on Days 1, 8, and 15 of each 21-day cycle.

Drug: Bevacizumab
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.

Experimental: Atezolizumab + Isatuximab
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.
Drug: Atezolizumab
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.

Drug: Isatuximab
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.

Experimental: Atezolizumab + Selicrelumab + Bevacizumab
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.
Drug: Atezolizumab
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.

Drug: Bevacizumab
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.

Drug: Selicrelumab
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.

Experimental: Atezolizumab + Idasanutlin
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.
Drug: Atezolizumab
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.

Drug: Idasanutlin
Idasanutlin will be administered orally on Days 1-5 of each 28-day cycle.

Experimental: Atezolizumab + Regorafenib
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.
Drug: Regorafenib
Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Drug: Atezolizumab
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.

Experimental: Atezolizumab + Regorafenib + AB928
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.
Drug: Regorafenib
Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Drug: Atezolizumab
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.

Drug: AB928
AB928 will be administered orally once daily on Days 1-28 of each 28-day cycle.




Primary Outcome Measures :
  1. Objective 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 Measures :
  1. 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) ]
  2. Overall Survival (OS) After Randomization [ Time Frame: From randomization up to death from any cause (up to approximately 3-5 years) ]
  3. Percentage of Participants Who Are Alive at Month 6 [ Time Frame: Month 6 ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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 (of each 21 or 28 day cycle); 30 days after last dose (up to approximately 3-5 years) ]
  8. Percentage of Participants with ADAs to Bevacizumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 3 and 4 (of each 21 or 28 day cycle); 30 days after last dose (up to approximately 3-5 years) ]
  9. 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 (up to approximately 3-5 years) ]
  10. Percentage of Participants with ADAs to Selicrelumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 2, 4, 8, 12 and 16 (cycle = 28 days); 30 days after last dose (up to approximately 3-5 years) ]
  11. 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, 3, 4, 8, 12, 16 (of each 21 or 28 day cycle); 30 days after last dose (up to approximately 3-5 years) ]
  12. 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 Cycle 3 (cycles = 21 days) or on Day 1 of Cycle 4 (cycle = 28 days); 30 days after last dose (up to approximately 3-5 years) ]
  13. 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) ]
  14. 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) ]
  15. Serum Concentration of Selicrelumab [ Time Frame: Pre-infusion (0 hour [hr]) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 4, 8, 12, 16 (each cycle=28 days); 30 days after last dose (up to approximately 3-5 years) ]
  16. Plasma Concentration of AB928 [ Time Frame: Pre-infusion (0hr), post infusion (30min),1,2,4,6hrs on Day1, 24hrs on Day2, 0hr on Days 8,15,22 of Cycle1; 0hr on Day1 of Cycles 2,3,4,8,12,16 (cycle=28 days); post infusion (30min),1,3hrs on Day1 of Cycle2; 30 days after last dose (up to 3-5 years) ]
  17. Plasma Concentration of Regorafenib [ Time Frame: Pre-dose (0 hour [hr]) on Days 1, 8, 15 and 22 of Cycle 1. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03555149


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: CO39612 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Show Show 20 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03555149    
Other Study ID Numbers: CO39612
2017-004566-99 ( EudraCT Number )
First Posted: June 13, 2018    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors