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)
Overview
- Phase
- Phase 1
- Intervention
- Regorafenib
- Conditions
- Colorectal Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 96
- Locations
- 15
- Primary Endpoint
- Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Regorafenib (Control)
Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Intervention: Regorafenib
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.
Intervention: Atezolizumab
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.
Intervention: Imprime PGG
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.
Intervention: Bevacizumab
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.
Intervention: Atezolizumab
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.
Intervention: Isatuximab
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.
Intervention: Atezolizumab
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.
Intervention: Bevacizumab
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.
Intervention: Selicrelumab
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.
Intervention: Atezolizumab
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.
Intervention: Idasanutlin
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.
Intervention: Regorafenib
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.
Intervention: Atezolizumab
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.
Intervention: Regorafenib
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.
Intervention: Atezolizumab
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.
Intervention: AB928
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.
Intervention: Atezolizumab
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.
Intervention: LOAd703
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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))
- Overall Survival (OS)(From randomization up to death from any cause (up to 4 years))
- 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))
- 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))
- Percentage of Participants With at Least One Adverse Event (AE)(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))