Colorectal CancerPhase 1/2NCT03555149

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

A Phase 1/2 study testing Regorafenib, Atezolizumab and Imprime PGG in people with Colorectal Cancer, run by Hoffmann-La Roche at 15 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Cancer
What is being tested?: Regorafenib, Atezolizumab and Imprime PGG
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 96 participants
Where: 15 sitesin 5 countries
Study dates: 27 Sep 2018to 26 Sep 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

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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

Trial locations and contacts

15 sites in 5 countries.

Country

City, postcode or hospital

15 sites in 5 countries

United States6 sites

Dana Farber Cancer Institute
Boston, Massachusetts, 02215
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Yale University
New Haven, Connecticut, 06511
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Washington University School of Medicine
St Louis, Missouri, 63110

Other trials in United States

France4 sites

Centre Georges François Leclerc; Pharmacie des Essais Cliniques
Dijon, 21079
Centre Leon Berard
Lyon, 69008
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, 31059
Institut Gustave Roussy
Villejuif, 94805

Other trials in France

South Korea3 sites

Seoul National University Hospital
Seoul, 03080
Samsung Medical Center
Seoul, 06351
Asan Medical Center.
Seoul, 5505

Other trials in South Korea

Australia1 site

Peter MacCallum Cancer Center
North Melbourne, Victoria, 3051

Other trials in Australia

Switzerland1 site

CHUV; Departement d'Oncologie
Lausanne, 1011

Other trials in Switzerland

About this study

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)

Conditions: Colorectal Cancer
Being tested: Regorafenib, Atezolizumab, Imprime PGG, Bevacizumab, Isatuximab
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RegorafenibDrug
Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.
AtezolizumabDrug
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 PGGDrug
Imprime PGG will be administered by IV infusion weekly on Days 1, 8, and 15 of each 21-day cycle.
BevacizumabDrug
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.
IsatuximabDrug
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.
SelicrelumabDrug
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.
IdasanutlinDrug
Idasanutlin will be administered orally on Days 1-5 of each 28-day cycle.
AB928Drug
AB928 will be administered orally once daily on Days 1-28 of each 28-day cycle.
LOAd703Genetic
Also called Delolimogene mupadenorepvec
LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.

Study groups in NCT03555149
Study group	Role	What they receive
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. Receives: Drug: Regorafenib
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. Receives: Drug: Atezolizumab; Drug: Imprime PGG; Drug: 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. Receives: Drug: Atezolizumab; Drug: Isatuximab
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. Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: 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. Receives: Drug: Atezolizumab; Drug: Idasanutlin
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. Receives: Drug: Regorafenib; Drug: Atezolizumab
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. Receives: Drug: Regorafenib; Drug: Atezolizumab; Drug: 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. Receives: Drug: Atezolizumab; Genetic: LOAd703

What is being measured

The primary outcome is the main question the study is designed to answer.

Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
The best confirmed overall response rate (ORR) is defined as the percentage of participants with a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to RECIST v1.1. Participants could be classified as "Stable Disease" if the assessment was at least 6 weeks from randomization. Participants were classified as Missing if no post-baseline response assessments were available. Participants were classified as Not Evaluable if all post-baseline response assessments were unevaluable. The differences in ORR between the experimental arms and the corresponding control arm were calculated, along with 95% confidence intervals (CIs), using normal approximation of the binomial distribution. The 95% CIs for ORRs were constructed using the Clopper-Pearson method. The 95% CIs for the difference in rates were constructed using the Wald method with continuity correction.
Measured: From randomization until disease progression or loss of clinical benefit (up to 4 years)

Secondary outcomes (6)

Progression-Free Survival (PFS) as Determined by Investigator According to RECIST v1.1
Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), was determined by the investigator according to RECIST v1.1. For participants who did not have documented disease progression or death, PFS was censored at the day of the last tumor assessment. The Kaplan-Meier method was used to estimate the median for PFS with 95% confidence intervals (CIs) constructed through use of the Brookmeyer and Crowley method.
Measured: From randomization up to the first occurrence of disease or death from any cause (up to 4 years)
Overall Survival (OS)
Overall survival (OS) is defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier method was used to estimate the median for OS with 95% confidence intervals (CIs) constructed through use of the Brookmeyer and Crowley method.
Measured: From randomization up to death from any cause (up to 4 years)
Percentage of Participants Who Were Alive at Landmark Timepoints for Overall Survival (OS)
Overall survival (OS) is defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. OS is shown as the percentage of participants who were event-free at the landmark timepoints of 3, 6, 12, and 18 months.
Measured: 3, 6, 12, and 18 months
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause.
Measured: 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)
Disease Control Rate (DCR), as Determined by the Investigator Per RECIST v1.1
Disease control rate is defined as the percentage of participants with stable disease for ≥12 weeks or a complete or partial response, as determined by the investigator according to RECIST v1.1.
Measured: From randomization until disease progression or loss of clinical benefit (up to 4 years)
Percentage of Participants With at Least One Adverse Event (AE)
The incidence, nature, and severity of adverse events (AEs) are reported, with severity determined according to NCI CTCAE v4.0. All AEs were reported until 30 days after the last study dose or until start of new systemic anti-cancer therapy. Serious AEs and AEs of special interest were reported until 135 days (or 180 days for the Atezolizumab + LOAd703 arm only) after the last dose of study treatment.
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Sep 201826 Sep 2022

First posted13 Jun 2018
Study start27 Sep 2018
Primary completion26 Sep 2022
Study completion26 Sep 2022

Why it stopped: The Sponsor made the decision to terminate the study due to start up and recruitment issues caused by limited resource availability at the treating centers.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Colorectal CancerStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 96 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03555149
Sponsor's protocol ID: CO39612
Other IDs: 2017-004566-99, 2017
Status last verified: Nov 2023
First submitted: 31 May 2018
Last updated: 7 Nov 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT03555149
Acronym / sponsor ID: CO39612
Conditions: Colorectal Cancer
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The Sponsor made the decision to terminate the study due to start up and recruitment issues caused by limited resource availability at the treating centers.
Enrolment: 96 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: 27 Sep 2018 (actual)
Primary completion: 26 Sep 2022 (actual)
Study completion: 26 Sep 2022 (actual)
First posted: 13 Jun 2018 (actual)
Results: Posted 7 Nov 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Regorafenib (Control)	Active comparator	Drug: RegorafenibParticipants 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	Drug: Atezolizumab, Drug: Imprime PGG, Drug: BevacizumabParticipants 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 + Isatuximab	Experimental	Drug: Atezolizumab, Drug: IsatuximabParticipants 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 + Selicrelumab + Bevacizumab	Experimental	Drug: Atezolizumab, Drug: Bevacizumab, Drug: SelicrelumabParticipants 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 + Idasanutlin	Experimental	Drug: Atezolizumab, Drug: IdasanutlinParticipants 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	Experimental	Drug: Regorafenib, Drug: AtezolizumabParticipants 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	Drug: Regorafenib, Drug: Atezolizumab, Drug: AB928Participants 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 + LOAd703	Experimental	Drug: Atezolizumab, Genetic: LOAd703Participants 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (29 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RegorafenibRegorafenib will be administered orally on Days 1-21 of each 28-day cycle.	Drug	Atezolizumab + Regorafenib, Atezolizumab + Regorafenib + AB928, Regorafenib (Control)
AtezolizumabAtezolizumab 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	Atezolizumab + Idasanutlin, Atezolizumab + Imprime PGG + Bevacizumab, Atezolizumab + Isatuximab, Atezolizumab + LOAd703, Atezolizumab + Regorafenib, Atezolizumab + Regorafenib + AB928, Atezolizumab + Selicrelumab + Bevacizumab
Imprime PGGImprime PGG will be administered by IV infusion weekly on Days 1, 8, and 15 of each 21-day cycle.	Drug	Atezolizumab + Imprime PGG + Bevacizumab
BevacizumabBevacizumab 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	Atezolizumab + Imprime PGG + Bevacizumab, Atezolizumab + Selicrelumab + Bevacizumab
IsatuximabIsatuximab 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.	Drug	Atezolizumab + Isatuximab
SelicrelumabSelicrelumab 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.	Drug	Atezolizumab + Selicrelumab + Bevacizumab
IdasanutlinIdasanutlin will be administered orally on Days 1-5 of each 28-day cycle.	Drug	Atezolizumab + Idasanutlin
AB928AB928 will be administered orally once daily on Days 1-28 of each 28-day cycle.	Drug	Atezolizumab + Regorafenib + AB928
LOAd703Also: Delolimogene mupadenorepvecLOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.	Genetic	Atezolizumab + LOAd703

Primary outcome

Best Confirmed Overall 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 4 years)
The best confirmed overall response rate (ORR) is defined as the percentage of participants with a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to RECIST v1.1. Participants could be classified as "Stable Disease" if the assessment was at least 6 weeks from randomization. Participants were classified as Missing if no post-baseline response assessments were available. Participants were classified as Not Evaluable if all post-baseline response assessments were unevaluable. The differences in ORR between the experimental arms and the corresponding control arm were calculated, along with 95% confidence intervals (CIs), using normal approximation of the binomial distribution. The 95% CIs for ORRs were constructed using the Clopper-Pearson method. The 95% CIs for the difference in rates were constructed using the Wald method with continuity correction.

6 secondary outcomes

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 4 years)
Overall Survival (OS)
Time frame: From randomization up to death from any cause (up to 4 years)
Percentage of Participants Who Were Alive at Landmark Timepoints for Overall Survival (OS)
Time frame: 3, 6, 12, and 18 months
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 4 years)
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 4 years)
Percentage of Participants With at Least One Adverse Event (AE)
Time frame: 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)

Results and safety

Results posted to the registry on 7 Nov 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Regorafenib (Control)	24	0
Atezolizumab + Imprime PGG + Bevacizumab	15	0
Atezolizumab + Isatuximab	15	0
Atezolizumab + Selicrelumab + Bevacizumab	6	0
Atezolizumab + Idasanutlin	4	0
Atezolizumab + Regorafenib	15	0
Atezolizumab + Regorafenib + AB928	15	0
Atezolizumab + LOAd703	2	0

Primary outcome: Best Confirmed Overall 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 4 years). Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Regorafenib (Control) n = 19	Atezolizumab + Imprime PGG + Bevacizumab n = 15	Atezolizumab + Isatuximab n = 15	Atezolizumab + Selicrelumab + Bevacizumab n = 6	Atezolizumab + Idasanutlin n = 4	Atezolizumab + Regorafenib n = 15	Atezolizumab + Regorafenib + AB928 n = 15	Atezolizumab + LOAd703 n = 2
Responders (CR + PR)	0 (0 to 17.65)	0 (0 to 21.80)	0 (0 to 21.80)	0 (0 to 45.93)	0 (0 to 60.24)	6.7 (0.17 to 31.95)	6.7 (0.17 to 31.95)	0 (0 to 84.19)
Complete Response (CR)	0 (0 to 17.65)	0 (0 to 21.80)	0 (0 to 21.80)	0 (0 to 45.93)	0 (0 to 60.24)	0 (0 to 21.80)	0 (0 to 21.80)	0 (0 to 84.19)
Partial Response (PR)	0 (0 to 17.65)	0 (0 to 21.80)	0 (0 to 21.80)	0 (0 to 45.93)	0 (0 to 60.24)	6.7 (0.17 to 31.95)	6.7 (0.17 to 31.95)	0 (0 to 84.19)
Stable Disease (SD)	63.2 (38.36 to 83.71)	33.3 (11.82 to 61.62)	20.0 (4.33 to 48.09)	50 (11.81 to 88.19)	0 (0 to 60.24)	33.3 (11.82 to 61.62)	53.3 (26.59 to 78.73)	0 (0 to 84.19)
Progressive Disease (PD)	26.3 (9.15 to 51.20)	66.7 (38.38 to 88.18)	66.7 (38.38 to 88.18)	33.3 (4.33 to 77.72)	100 (39.76 to 100)	46.7 (21.27 to 73.41)	26.7 (7.79 to 55.10)	100 (15.81 to 100)
Not Evaluable	0 (NA to NA)	0 (NA to NA)	13.3 (NA to NA)	0 (NA to NA)	0 (NA to NA)	0 (NA to NA)	13.3 (NA to NA)	0 (NA to NA)
Missing	10.5 (NA to NA)	0 (NA to NA)	0 (NA to NA)	16.7 (NA to NA)	0 (NA to NA)	13.3 (NA to NA)	0 (NA to NA)	0 (NA to NA)

Regorafenib (Control) vs Atezolizumab + Regorafenib: Difference in Overall Response Rate: 6.67 (95% CI -11.92 to 25.25)
Regorafenib (Control) vs Atezolizumab + Regorafenib + AB928: Difference in Overall Response Rate: 6.67 (95% CI -11.92 to 25.25)

Population analysed: The efficacy evaluable population included all patients who received at least one dose of each drug for their assigned treatment regimen.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected from first study dose up to 6 months after the last dose of study treatment (up to 640 days); deaths (all-cause) were reported from enrolment through survival follow-up (up to 4 years).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Regorafenib (Control)	5 of 19 (26.3%)	19 of 19 (100%)	18 of 24
Atezolizumab + Imprime PGG + Bevacizumab	1 of 15 (6.7%)	15 of 15 (100%)	15 of 15
Atezolizumab + Isatuximab	5 of 15 (33.3%)	15 of 15 (100%)	15 of 15
Atezolizumab + Selicrelumab + Bevacizumab	3 of 6 (50%)	6 of 6 (100%)	4 of 6
Atezolizumab + Idasanutlin	1 of 4 (25%)	4 of 4 (100%)	4 of 4
Atezolizumab + Regorafenib	7 of 15 (46.7%)	15 of 15 (100%)	11 of 15
Atezolizumab + Regorafenib + AB928	7 of 15 (46.7%)	15 of 15 (100%)	12 of 15
Atezolizumab + LOAd703	1 of 2 (50%)	2 of 2 (100%)	1 of 2

Limitations and caveats (from the sponsor): This study is not designed to make explicit power and Type I error considerations for a hypothesis test. Instead, this study is designed to obtain preliminary efficacy, safety, and PK data. No formal statistical hypothesis testing was performed in this study. Due to the limited sample size, the results need to be interpreted with caution. For the Atezo+Idasa and Atezo+LOAd703 groups, no meaningful conclusion could be drawn because these experimental arms have been terminated prematurely.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

15 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Regorafenib, Atezolizumab and Imprime PGG in people with Colorectal Cancer, run by Hoffmann-La Roche at 15 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, France, South Korea, Australia, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best Confirmed Overall 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 4 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03555149.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.