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

NCT ID: NCT03555149

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-27
• Study Completion Date: 2022-09-26

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regorafenib (Control)

Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Group Type: ACTIVE_COMPARATOR

Regorafenib

Intervention Type: DRUG

Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Imprime PGG

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Isatuximab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Bevacizumab

Intervention Type: DRUG

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.

Selicrelumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

Idasanutlin

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Regorafenib

Intervention Type: DRUG

Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Regorafenib

Intervention Type: DRUG

Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

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.

AB928

Intervention Type: DRUG

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

Atezolizumab + LOAd703

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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.

LOAd703

Intervention Type: GENETIC

LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.

Interventions

Regorafenib

Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Intervention Type: 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.

Intervention Type: DRUG

Imprime PGG

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Idasanutlin

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

Intervention Type: DRUG

AB928

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

Intervention Type: DRUG

LOAd703

LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.

Intervention Type: GENETIC

Other Intervention Names

Delolimogene mupadenorepvec

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Yale University

New Haven, Connecticut, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Peter MacCallum Cancer Center

North Melbourne, Victoria, Australia

Centre Georges François Leclerc; Pharmacie des Essais Cliniques

Dijon, , France

Centre Leon Berard

Lyon, , France

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center.

Seoul, , South Korea

CHUV; Departement d'Oncologie

Lausanne, , Switzerland

Countries

United States; Australia; France; South Korea; Switzerland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-004566-99

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CO39612

Identifier Type: -

Identifier Source: org_study_id