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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03555149




Registration number
NCT03555149
Ethics application status
Date submitted
31/05/2018
Date registered
13/06/2018
Date last updated
7/11/2023

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)
Scientific 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)
Secondary ID [1] 0 0
2017-004566-99
Secondary ID [2] 0 0
CO39612
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Regorafenib
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Imprime PGG
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Isatuximab
Treatment: Drugs - Selicrelumab
Treatment: Drugs - Idasanutlin
Treatment: Drugs - AB928
Treatment: Other - LOAd703

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.

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.

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.

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.

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.

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.

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.

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.


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

Treatment: Drugs: 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.

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

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

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

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

Treatment: Other: LOAd703
LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Timepoint [1] 0 0
From randomization until disease progression or loss of clinical benefit (up to 4 years)
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) as Determined by Investigator According to RECIST v1.1
Timepoint [1] 0 0
From randomization up to the first occurrence of disease or death from any cause (up to 4 years)
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From randomization up to death from any cause (up to 4 years)
Secondary outcome [3] 0 0
Percentage of Participants Who Were Alive at Landmark Timepoints for Overall Survival (OS)
Timepoint [3] 0 0
3, 6, 12, and 18 months
Secondary outcome [4] 0 0
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
Timepoint [4] 0 0
From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 4 years)
Secondary outcome [5] 0 0
Disease Control Rate (DCR), as Determined by the Investigator Per RECIST v1.1
Timepoint [5] 0 0
From randomization until disease progression or loss of clinical benefit (up to 4 years)
Secondary outcome [6] 0 0
Percentage of Participants With at Least One Adverse Event (AE)
Timepoint [6] 0 0
Adverse event data were collected from baseline up to 6 months after the last dose of study treatment (up to 640 days); deaths (all-cause) were reported from baseline through survival follow-up (up to 4 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/09/2022
Sample size
Target
Accrual to date
Final
96
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Center - North Melbourne
Recruitment postcode(s) [1] 0 0
3051 - North Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
France
State/province [6] 0 0
Dijon Cedex
Country [7] 0 0
France
State/province [7] 0 0
Lyon
Country [8] 0 0
France
State/province [8] 0 0
Toulouse
Country [9] 0 0
France
State/province [9] 0 0
Villejuif
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Switzerland
State/province [11] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03555149
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03555149