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

NCT03555149 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CO396122017-004566-99
• Study Type: interventional
• Target: 96
• Locations: 5 countries
• Sites: 15

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  From randomization up to the first occurrence of disease or death from any cause (up to 4 years)

• Overall Survival (OS)

  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)

  3, 6, 12, and 18 months

• 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 4 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 4 years)

Study Arms (8)

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.

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.

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.

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.

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.

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.

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.

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.

Drug: Atezolizumab; Genetic: LOAd703

Interventions

Regorafenib DRUG

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

Atezolizumab + Regorafenib; Atezolizumab + Regorafenib + AB928; Regorafenib (Control)

Atezolizumab 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 + Idasanutlin; Atezolizumab + Imprime PGG + Bevacizumab; Atezolizumab + Isatuximab; Atezolizumab + LOAd703; Atezolizumab + Regorafenib; Atezolizumab + Regorafenib + AB928; Atezolizumab + Selicrelumab + Bevacizumab

Imprime PGG DRUG

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

Atezolizumab + Imprime PGG + Bevacizumab

Bevacizumab 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 + Imprime PGG + Bevacizumab; Atezolizumab + Selicrelumab + Bevacizumab

Isatuximab 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 + Isatuximab

Selicrelumab 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 + Selicrelumab + Bevacizumab

Idasanutlin DRUG

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

Atezolizumab + Idasanutlin

AB928 DRUG

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

Atezolizumab + Regorafenib + AB928

LOAd703 GENETIC

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

Also known as: Delolimogene mupadenorepvec

Atezolizumab + LOAd703

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (15)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Peter MacCallum Cancer Center

North Melbourne, Victoria, 3051, Australia

Location

Centre Georges François Leclerc; Pharmacie des Essais Cliniques

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Asan Medical Center.

Seoul, 5505, South Korea

Location

CHUV; Departement d'Oncologie

Lausanne, 1011, Switzerland

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib; atezolizumab; Bevacizumab; isatuximab; selicrelumab; RG7388

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

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.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: June 13, 2018
• Study Start: September 27, 2018
• Primary Completion: September 26, 2022
• Study Completion: September 26, 2022
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-11

Locations

FR (4); US (6); KR (3); CH (1); AU (1)