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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03555149

Collaborator

(none)

382

Enrollment

Locations

Arms

61.9

Anticipated Duration (Months)

21.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

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 Genetic: LOAd703	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

382 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 :

Sep 27, 2018

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Nov 25, 2023

Arms and Interventions

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. Enrollment closed.	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. Enrollment closed.	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. Enrollment closed.	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. Enrollment closed.	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.
Experimental: 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.	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. Genetic: LOAd703 LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle. Other Names: Delolimogene mupadenorepvec

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years)]

Secondary Outcome Measures

Progression Free Survival (PFS) as Determined by Investigator According to RECIST v1.1 [From randomization up to the first occurrence of disease or death from any cause (up to approximately 3-5 years)]
Overall Survival (OS) After Randomization [From randomization up to death from any cause (up to approximately 3-5 years)]
Percentage of Participants Who Are Alive at Month 6 [Month 6]
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 [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)]
Disease Control Rate (DCR), as Determined by the Investigator per RECIST v1.1 [From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years)]
Percentage of Participants with Adverse Events (AEs) [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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	Yale University	New Haven	Connecticut	United States	06511
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	Columbia University Medical Center	New York	New York	United States	10032
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
7	Peter MacCallum Cancer Center	North Melbourne	Victoria	Australia	3051
8	Centre Georges François Leclerc; Pharmacie des Essais Cliniques	Dijon Cedex		France	21079
9	Centre Leon Berard	Lyon		France	69008
10	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse		France	31059
11	Institut Gustave Roussy	Villejuif		France	94805
12	Seoul National University Hospital	Seoul		Korea, Republic of	03080
13	Samsung Medical Center	Seoul		Korea, Republic of	06351
14	Asan Medical Center.	Seoul		Korea, Republic of	138-736
15	Universidad de Navarra - Clinica Universitaria de Navarra (CUN)	Pamplona	Navarra	Spain	31008
16	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
17	CHUV; Departement d'Oncologie	Lausanne		Switzerland	1011
18	Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)-CECM	London		United Kingdom	0

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT03555149

Other Study ID Numbers:

CO39612
2017-004566-99

First Posted:

Jun 13, 2018

Last Update Posted:

Aug 5, 2022

Last Verified:

Aug 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Colorectal Neoplasms

Bevacizumab

Atezolizumab

Study Results

No Results Posted as of Aug 5, 2022