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A Phase Ib Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Cibisatamab in Combination With Atezolizumab After Pretreatment With Obinutuzumab in Participants With Previously Treated Metastatic Colorectal Adenocarcinoma

NCT03866239

Description:

CO40939 is a Phase Ib, open-label, multicenter, single-arm study designed to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of cibisatamab in combination with atezolizumab administered after pretreatment with obinutuzumab in patients with Stage IV microsatellite stable (MSS) metastatic colorectal cancer (mCRC) whose tumors have high carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression and who have progressed on two or more chemotherapy regimens. The study is composed of a safety run-in and an exploratory part.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase Ib Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Cibisatamab in Combination With Atezolizumab After Pretreatment With Obinutuzumab in Participants With Previously Treated Metastatic Colorectal Adenocarcinoma
  • Official Title: A Phase Ib, Multicenter, Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Cibisatamab in Combination With Atezolizumab After Pretreatment With Obinutuzumab in Patients With Previously Treated Metastatic, Microsatellite-Stable Colorectal Adenocarcinoma With High CEACAM5 Expression

Clinical Trial IDs

  • ORG STUDY ID: CO40939
  • SECONDARY ID: 2018-003198-93
  • NCT ID: NCT03866239

Conditions

  • Colorectal Cancer

Interventions

DrugSynonymsArms
ObinutuzumabGazyva/GazyvaroObinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab
AtezolizumabTecentriqObinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab
CibisatamabObinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab
TocilizumabObinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab

Purpose

CO40939 is a Phase Ib, open-label, multicenter, single-arm study designed to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of cibisatamab in combination with atezolizumab administered after pretreatment with obinutuzumab in patients with Stage IV microsatellite stable (MSS) metastatic colorectal cancer (mCRC) whose tumors have high carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression and who have progressed on two or more chemotherapy regimens. The study is composed of a safety run-in and an exploratory part.

Trial Arms

NameTypeDescriptionInterventions
Obinutuzumab Pretreatment (OpT) + Cibisatamab + AtezolizumabExperimentalParticipants will receive obinutuzumab approximately 2 weeks before receiving atezolizumab and cibisatamab on Day 1 of each treatment cycle (cycle = 21 days).
  • Obinutuzumab
  • Atezolizumab
  • Cibisatamab
  • Tocilizumab

Eligibility Criteria

        Inclusion criteria

          -  Histologically confirmed adenocarcinoma originating from the colon or rectum

          -  Metastatic disease not amenable to local treatment

          -  Tumors that are microsatellite stable or microsatellite instability low, as determined
             by a local, certified laboratory

          -  Tumors that have high carcinoembryonic antigen-related cell adhesion molecule 5
             (CEACAM5) expression as determined by quantitative reverse transcription polymerase
             chain reaction in a fresh tumor biopsy (for the safety run-in, CEACAM5 expression can
             be determined on the archival tumor tissue) and documented through central testing of
             a representative tumor tissue specimen performed at baseline

          -  Experienced disease progression during or within 3 months following the last
             administration of approved standard therapies

          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1

          -  Life expectancy of >= 12 weeks

          -  Adequate hematologic and end-organ function

          -  Negative HIV test at screening

          -  Negative hepatitis B surface antigen test and total hepatitis B core antibody (HBcAb)
             test at screening, or positive total HBcAb test followed by a negative hepatitis B
             virus (HBV) DNA test at screening

          -  Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
             test followed by a negative HCV RNA test at screening

          -  Negative human T-cell lymphotropic virus type 1 test for participants from endemic
             countries (Japan, countries in the Caribbean basin, South America, Central America,
             sub-Saharan Africa, and Malaysia)

          -  For women of childbearing potential: agreement to remain abstinent or use
             contraceptive methods, agreement to regular pregnancy testing, and agreement to
             refrain from donating eggs, women must remain abstinent or use contraceptive methods
             with a failure rate of < 1% per year during the treatment period and for 5 months
             after the final dose of atezolizumab, for 4 months after the final dose of
             cibisatamab, for 18 months after the final dose of obinutuzumab, and for 3 months
             after the final dose of tocilizumab

          -  For men: agreement to remain abstinent or use a condom, and agreement to refrain from
             donating sperm, with a female partner of childbearing potential or pregnant female
             partner, men must remain abstinent or use a condom during the treatment period and for
             3 months after the final dose of cibisatamab, for 3 months after the final dose of
             obinutuzumab, and for 2 months after the final dose of tocilizumab to avoid exposing
             the embryo

        Additional Inclusion Criteria for patient enrollment into Part 2 of the study:

        - No prior treatment with regorafenib or Trifluridine/Tipiracil (TAS-102)

        Exclusion criteria

          -  Symptomatic, untreated, or actively progressing central nervous system metastases

          -  Non-irradiated tumor lesions > 2 cm at critical sites where tumor swelling induced by
             cibisatamab is expected to lead to significant complications

          -  Dyspnea or peripheral capillary oxygen saturation < 92% at rest at baseline for
             patients with bilateral lung lesions or metastases in the remaining lung following
             lobectomy or pneumonectomy

          -  Spinal cord compression not definitively treated with surgery and/or radiation or
             previously diagnosed and treated spinal cord compression without evidence that disease
             has been clinically stable for >= 2 weeks prior to initiation of study treatment

          -  History of leptomeningeal disease and progressive multifocal leukoencephalopathy

          -  Uncontrolled tumor-related pain and pleural effusion or ascites requiring recurrent
             drainage procedures

          -  Patients with pericardial effusion

          -  Uncontrolled or symptomatic hypercalcemia

          -  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 scan

          -  Active tuberculosis that has required treatment within 3 years prior initiation of
             study treatment or latent tuberculosis that has not been appropriately treated

          -  Uncontrolled hypertension, unstable angina, congestive heart failure of any New York
             Heart Association Class II or greater, serious cardiac arrhythmia requiring treatment
             and history of myocardial infarction within 6 months 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 malignancy other than CRC within 5 years prior to screening, with the
             exception of malignancies with a negligible risk of metastasis or death, such as
             adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
             localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

          -  Known active infection, or reactivation of a latent infection, whether bacterial,
             viral, fungal, mycobacterial, or other pathogens, or any major episode of infection
             requiring hospitalization or treatment with IV antibiotics

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that contraindicates the use of an investigational drug, may affect
             the interpretation of the results, or may render the patient at high risk from
             treatment complications

          -  Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
             treatment, or anticipation of need for such a vaccine during study treatment or within
             5 months after the final dose of atezolizumab

          -  Current treatment with anti-viral therapy for HBV

          -  Treatment with any systemic anti-cancer therapy, including chemotherapy or hormonal
             therapy, within 28 days prior to initiation of study treatment

          -  Treatment with investigational therapy within 28 days prior to initiation of study
             treatment

          -  Prior treatment with any of the protocol-specified study treatments

          -  Prior treatment with T-cell bispecifics (TCBs), including CEACAM5-TCB, CD137 agonists
             or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and
             anti-PD-L1 therapeutic antibodies

          -  Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the
             drug prior to initiation of study treatment

          -  Treatment with systemic immunosuppressive medication within 2 weeks prior to
             initiation of study treatment, or anticipation of need for systemic immunosuppressive
             medication during study treatment

          -  Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or
             better with the exception of alopecia of any grade and Grade <= 2 peripheral
             neuropathy

          -  History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
             or fusion proteins

          -  Known hypersensitivity to Chinese hamster ovary cell products

          -  Known allergy or hypersensitivity to any of the study drugs or any of their excipients

          -  Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
             or within 5 months after the final dose of atezolizumab, within 4 months after the
             final dose of cibisatamab, within 18 months after the final dose of obinutuzumab, and
             within 3 months after the final dose of tocilizumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events (AEs)
Time Frame:Up to 5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Confirmed ORR, as Determined by an Independent Review Facility (IRF) According to Response Evaluation in Solid Tumors version 1.1 (RECIST v1.1)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years)
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 5 years)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From enrollment to death from any cause (up to 5 years)
Safety Issue:
Description:
Measure:Total Clearance (CL) for Cibisatamab
Time Frame:At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years)
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State (Vss) of Cibisatamab
Time Frame:At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years)
Safety Issue:
Description:
Measure:Area Under the Concentration-Time Curve (AUC0-t) for Cibisatamab
Time Frame:At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years)
Safety Issue:
Description:
Measure:Maximum Serum Concentration (Cmax) of Cibisatamab
Time Frame:At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years)
Safety Issue:
Description:
Measure:CL of Atezolizumab
Time Frame:At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:Vss of Atezolizumab
Time Frame:At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:AUC0-t of Atezolizumab
Time Frame:At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:Cmax of Atezolizumab
Time Frame:At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:CL of Obinutuzumab
Time Frame:At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:Vss of Obinutuzumab
Time Frame:At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:AUC0-t of Obinutuzumab
Time Frame:At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:Cmax of Obinutuzumab
Time Frame:At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days)
Safety Issue:
Description:
Measure:Incidence of Anti-Drug Antibodies (ADAs) to Cibisatamab
Time Frame:Baseline up to 5 years
Safety Issue:
Description:
Measure:Incidence of ADAs to Atezolizumab
Time Frame:Baseline up to 5 years
Safety Issue:
Description:
Measure:Incidence of ADAs to Obinutuzumab
Time Frame:Baseline up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

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