Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Atezolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

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

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

Regorafenib

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

Imprime PGG

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.

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.

Isatuximab

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.

Selicrelumab

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

Idasanutlin

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

AB928

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

LOAd703

Clinical Trials

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.

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

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)

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.

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.

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.

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.

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.

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.

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.

Hoffmann-La Roche

All-Cause Mortality is reported in the all-enrolled patients population. Adverse events (AEs) are reported in the safety population, defined as all those who received ≥1 dose of study treatment. One participant in the Regorafenib arm died before receiving study dose. All AEs were reported until 30 days after the last study dose or until the start of new systemic anti-cancer therapy. Serious AEs and AEs of special interest are reported until up to 180 days after last study dose.

Regorafenib (Control)

Atezolizumab + Imprime PGG + Bevacizumab

Atezolizumab + Isatuximab

Atezolizumab + Selicrelumab + Bevacizumab

Atezolizumab + Idasanutlin

Atezolizumab + Regorafenib

Atezolizumab + Regorafenib + AB928

Atezolizumab + LOAd703

Total

Age (year)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ECOG performance status scale. 0 - Fully active; able to carry on all predisease performance without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature

ECOG score

Number of Metastatic Sites at Enrollment

All participants who were randomized in the study, regardless of whether they actually received any study treatment.

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.

Medical Communications

Responders (CR + PR)

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Not Evaluable

Missing

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

Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Progression-Free Survival (PFS) as Determined by Investigator According to RECIST v1.1

Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Isatuximab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Idasanutlin vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Regorafenib vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + LOAd703 vs. Regorafenib (Control) Hazard Ratio for OS

The efficacy evaluable population included all participants who received at least one dose of each study drug for their assigned treatment regimen.

Overall Survival (OS)

Difference in OS event-free rate at 3 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab +LOAd703 vs. Regorafenib (Control) arms

3 Months

6 Months

12 Months

18 Months

The efficacy evaluable population included all participants who received at least one dose of each study drug for their assigned treatment regimen. The number analyzed at each landmark timepoint indicates the number of participants who were remaining at risk for an event. The event-free rate was not estimable (NE) for landmark timepoints at which 0 participants were remaining at risk for an an event.

Percentage of Participants Who Were Alive at Landmark Timepoints for Overall Survival (OS)

The duration of response analysis included all participants from the efficacy evaluable population who had a confirmed overall response; only 1 participant in each of the atezolizumab + regorafenib arm and the atezolizumab + regorafenib + AB928 arm had a confirmed response.

Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1

Disease Control Rate (DCR), as Determined by the Investigator Per RECIST v1.1

Adverse Event (AE)

Death

Withdrawn from Stage due to an AE

AE with a Fatal Outcome

Serious AE (SAE)

SAE Leading to Withdrawal from any Treatment

SAE Leading to Dose Modification/Interruption

Related SAE

AE Leading to Withdrawal from any Treatment

AE Leading to Dose Modification/Interruption

Related AE

Related AE Leading to Withdrawal from any Treatment

Related AE Leading to Dose Modification/Interruption

Grade 3-5 AE

Worst Grade AE: 5

Worst Grade AE: 4

Worst Grade AE: 3

The safety-evaluable population included all patients who received any amount of dose of any component of study treatment.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial