CO39612_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.
Indication :

Cancer coloréctal métastatique


Sponsor :

ROCHE


Phase :

I, II


Ligne :

3d


Traitement :

Multiple immunotherapy-based treatment combinations (Regorafenib (Control), Atezolizumab +Idasanutlin)


Site :

CHUV


Contact(s) :
Stefan Zimmermann
Investigateur Principal

CHUV
Service de Immuno-Oncologie

Rue du Bugnon 46
Lausanne
1011

0213143854
do.ion.ref@chuv.ch

Primary objective :

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in patients with metastatic CRC.


Inclusion criteria :

Ages Eligible for Study: 18 Years and older
Sexes Eligible for Study: All

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Life expectancy ≥ 3 months, as determined by the investigator
Disease progression during or following two (but not more) separate lines of treatment for metastatic colorectal cancer (mCRC) that consisted of fluoropyrimidine-, oxaliplatin-, or 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
Mutation in the BRAF oncogene
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