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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Regorafenib | | Atezolizumab + Regorafenib |
| Atezolizumab | | Atezolizumab + Idasanutlin |
| Imprime PGG | | Atezolizumab + Imprime PGG + Bevacizumab |
| Bevacizumab | | Atezolizumab + Imprime PGG + Bevacizumab |
| Isatuximab | | Atezolizumab + Isatuximab |
| Selicrelumab | | Atezolizumab + Selicrelumab + Bevacizumab |
| Idasanutlin | | Atezolizumab + Idasanutlin |
| AB928 | | Atezolizumab + Regorafenib + AB928 |
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) that became
refractory to first- and second-line standard therapies. Eligible patients will be assigned
to one of several treatment arms.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Regorafenib (Control) | Active Comparator | Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. | |
| Atezolizumab + Imprime PGG + Bevacizumab | Experimental | 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.
Enrollment closed. | - Atezolizumab
- Imprime PGG
- Bevacizumab
|
| Atezolizumab + Isatuximab | Experimental | 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.
Enrollment closed. | |
| Atezolizumab + Selicrelumab + Bevacizumab | Experimental | 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.
Enrollment closed. | - Atezolizumab
- Bevacizumab
- Selicrelumab
|
| Atezolizumab + Idasanutlin | Experimental | 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.
Enrollment closed. | |
| Atezolizumab + Regorafenib | Experimental | 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. | |
| Atezolizumab + Regorafenib + AB928 | Experimental | 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. | - Regorafenib
- Atezolizumab
- AB928
|
| Atezolizumab + LOAd703 | Experimental | 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. | |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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) |
| 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 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 18, 2021
