Clinical Trials /

Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment

NCT04826003

Description:

This is an open-label, multicenter, Phase Ib study to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) in the weekly (QW) and/or every 3 weeks (Q3W) regimens, safety, tolerability, PK, immunogenicity, PD profile and to evaluate preliminary anti-tumor activity of RO7122290 in combination with cibisatamab Q3W after pretreatment with obinutuzumab, in participants with previously treated metastatic, microsatellite-stable colorectal adenocarcinoma with high CEACAM5 expression

Related Conditions:
  • Colon Adenocarcinoma
  • Rectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment
  • Official Title: An Open-Label, Multicenter, Phase Ib Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290, A Fibroblast Activation Protein-A (FAP) Targeted 4-1BB Ligand (CD137L), In Combination With Cibisatamab With Obinutuzumab Pre-Treatment, In Participants With Previously Treated, Metastatic, Microsatellite-stable Colorectal Adenocarcinoma With High CEACAM5 Expression

Clinical Trial IDs

  • ORG STUDY ID: BP42675
  • NCT ID: NCT04826003

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
RO7122290Part I: Dose-escalation of RO7122290
CibisatamabPart I: Dose-escalation of RO7122290
ObinutuzumabPart I: Dose-escalation of RO7122290

Purpose

This is an open-label, multicenter, Phase Ib study to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) in the weekly (QW) and/or every 3 weeks (Q3W) regimens, safety, tolerability, PK, immunogenicity, PD profile and to evaluate preliminary anti-tumor activity of RO7122290 in combination with cibisatamab Q3W after pretreatment with obinutuzumab, in participants with previously treated metastatic, microsatellite-stable colorectal adenocarcinoma with high CEACAM5 expression

Trial Arms

NameTypeDescriptionInterventions
Part I: Dose-escalation of RO7122290ExperimentalThe dose-escalation of RO7122290 will use a QW dosing schedule of RO7122290 in combination with a Q3W dosing interval for cibisatamab with obinutuzumab pre-treatment. The starting dose for RO7122290 will be 35 mg, which represents the human equivalent dose for the minimal pharmacologically active dose (1 mg/kg) in mice.
  • RO7122290
  • Cibisatamab
  • Obinutuzumab
Part II: Dose-expansion of RO7122290ExperimentalPart II of this study will evaluate selected dose levels of RO7122290 from Part I (a QW RO712290 administration in combination with a Q3W cibisatamab administration with obinutuzumab pre-treatment) in a Q3W regimen in combination with a Q3W cibisatamab administration with obinutuzumab pre-treatment.
  • RO7122290
  • Cibisatamab
  • Obinutuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma originating from the colon or rectum.

          -  Metastatic disease (Stage IV American Joint Committee on Cancer, Version 7) not
             amenable to local treatment.

          -  Tumors that are MSS (microsatellite-stable) or MSI-low (microsatellite instable low),
             as determined by a certified laboratory

          -  Participants with tumors that have high CEACAM5 expression as determined by qRT-PCR in
             an archival tumor sample or if not available, in a fresh tumor biopsy 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 organ functions.

          -  Serum creatinine within normal limits or a calculated glomerular filtration rate of ≥
             60 mL/min/1.73 m2 for participants with serum creatinine levels above or below the
             institutional normal value.

          -  Serum albumin ≥30 g/L (3.0 g/dL).

          -  Lactate dehydrogenase ≤ 2.5 x ULN.

          -  Adequate contraception

        Exclusion Criteria:

          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)
             metastases.

          -  History of leptomeningeal disease

          -  Non-irradiated tumor lesions > 2 cm at critical sites (e.g., paraspinal, paratracheal,
             mediastinal, precarnial, sub-glottal) where tumor swelling induced by cibisatamab is
             expected to lead to significant complications. Irradiation must be completed at least
             14 days prior to initiation of study treatment.

          -  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

          -  Pleural effusion requiring drainage procedures.

          -  Pleural effusion and/or pleural lesions involving both lungs

          -  Active interstitial lung disease (ILD), pneumonitis, or a history of ILD/pneumonitis
             requiring treatment with steroids or history of idiopathic pulmonary fibrosis,
             organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or
             idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

          -  History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

          -  Severe dyspnea at rest due to complications of advanced malignancy or requiring
             supplementary oxygen therapy.

          -  Patients with > 10 bilateral pulmonary lesions

          -  Patients with pulmonary miliary metastatic pattern (innumerable small lesions) or
             pulmonary lymphangitic carcinomatosis.

          -  Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of
             study drug administration

          -  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 progressive multifocal leukoencephalopathy

          -  Uncontrolled tumor-related pain.

          -  Uncontrolled ascites requiring recurrent drainage procedures (QW or more frequently).
             Participants with indwelling catheters are allowed.

          -  Patients with pericardial effusion.

          -  Uncontrolled or symptomatic hypercalcemia

          -  Active or history of autoimmune disease or immune deficiency, including, but not
             limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
             antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome,
             or multiple sclerosis for a more comprehensive list of autoimmune diseases and immune
             deficiencies).

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

          -  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 (e.g., 5-year
             OS rate > 90%), 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.

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including diabetes
             mellitus, history of relevant pulmonary disorders, or other disease with ongoing
             fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis,
             palmar/plantar fibromatosis).

          -  Known active infection, or reactivation of a latent infection, whether bacterial,
             viral (including, but not limited to, Epstein-Barr virus infection), fungal,
             mycobacterial, or other pathogens (excluding fungal infections of nail beds), or any
             major episode of infection requiring hospitalization or treatment with systemic
             antibiotics (IV and oral antibiotic treatment must have been completed at least 4 and
             2 weeks, respectively, prior to initiation of study treatment).

          -  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.

          -  History of chronic liver disease or evidence of hepatic cirrhosis.

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that give reasonable suspicion of a disease or condition that would
             contraindicate the use of an investigational drug.

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
             and to chimeric or humanized antibodies or fusion proteins.

          -  Major surgery or significant traumatic injury < 28 days prior to the first
             obinutuzumab infusion (excluding biopsies) or anticipation of the need for major
             surgery during study treatment.

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

          -  Prior treatment with T-cell bispecifics (TCBs), CD137 (4-1BB) agonists or immune
             checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1
             therapeutic antibodies, unless discussed and agreed by the Sponsor.

          -  Treatment with systemic immunostimulatory agents (including, but not limited to,
             interferon and IL-2) within 4 weeks or 5 half-lives (whatever if longer) prior to
             initiation of study treatment.

          -  Treatment with systemic immunosuppressive medication (including, but not limited to,
             corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
             anti-TNF-alpha agents) 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.

          -  Known hypersensitivity to Chinese hamster ovary cell products.

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

          -  Any participant actively taking anti platelet medication (aspirin, clopidogrel,
             ticagrelor, etc.) or any participant who is fully anti coagulated with warfarin, low
             molecular weight heparin or a novel oral anti-coagulant including dabigatran,
             rivaroxaban, epixaban, etc.

          -  Pregnancy or breastfeeding, or intention of becoming pregnant during the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part I: Occurrence of dose-limiting toxicities
Time Frame:Baseline up to 21 days
Safety Issue:
Description:The DLT observation period is defined as a period of 21 days after the first administration of RO7122290 combined with cibisatamab. Additional days (maximum 3 days per dosing) are allowed in case of treatment delays for non-safety reasons. Participants are evaluable for DLT assessment, if they have received one dose of cibisatamab and at least two doses of RO7122290 during the DLT period.

Secondary Outcome Measures

Measure:Serum concentration of RO7122290 over time
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Plasma concentration of RO7122290 over time
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Maximum concentration (Cmax) of RO7122290
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Time of maximum concentration (Tmax) of RO7122290
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Clearance (CL) of RO7122290
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Volume of distribution (V) of RO7122290
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Area under the curve (AUC) of RO7122290
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Half-life (t1/2) of RO7122290
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290. Part II: Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days
Measure:Serum concentration of Cibisatamab over time
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Plasma concentration of Cibisatamab over time
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Maximum concentration (Cmax) of Cibisatamab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Time of maximum concentration (Tmax) of Cibisatamab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Clearance (CL) of Cibisatamab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Volume of distribution (V) of Cibisatamab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Area under the curve (AUC) of Cibisatamab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Half-life (t1/2) of Cibisatamab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Part I: Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit Part II: Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Serum concentration of Obinutuzumab over time
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Plasma concentration of Obinutuzumab over time
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Maximum concentration (Cmax) of Obinutuzumab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Time of maximum concentration (Tmax) of Obinutuzumab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Clearance (CL) of Obinutuzumab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Volume of distribution (V) of Obinutuzumab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Area under the curve (AUC) of Obinutuzumab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Half-life (t1/2) of Obinutuzumab
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days
Measure:Percentage of Participants with RO7122290 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Cycle 1: Day 1, 8, 15; Cycles 3, 4, 6, 8: Day 1; Discontinuation visit. Each cycle is 21 days
Measure:Percentage of Participants with Cibisatamab anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Cycle 1 Day 1 (Predose, 15 minutes postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); Day 8 (Predose); C3-16 D1, then every 4th cycle; Discontinuation visit. Each cycle is 21 days
Measure:Percentage of Participants with Obinutuzumab anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: Day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); C3, 4, 6, 8 Day 1; Discontinuation visit. Each cycle is 21 days
Measure:Treatment-induced change on T-cell proliferation (CD8/Ki67)
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on T-cell activation (CD8/4-1BB)
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on tumor necrosis factor alpha (TNF-alpha) levels
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on interferon gamma (IFN-gamma) levels
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on Interleukin (IL)-2 levels
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on Interleukin (IL)-6 levels
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on Interleukin (IL)-8 levels
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on Interleukin (IL)-10 levels
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Treatment-induced change on Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels
Time Frame:Baseline up to 28 months (detailed time frame provided in description)
Safety Issue:
Description:Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days
Measure:Objective response rate (ORR) defined as complete response (CR) + partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Baseline up to 28 months
Safety Issue:
Description:Objective response rate (ORR) is determined as the rate of participants with an objective tumor response of CR or PR. ORR will be derived for RECIST Version 1.1 and will be based on Investigators' assessment.
Measure:Disease control rate (DCR); defined as response rate (RR) + stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Baseline up to 28 months
Safety Issue:
Description:Disease control rate (DCR) is determined as the rate of participants with an objective tumor response of CR, PR or SD. DCR will be derived for RECIST Version 1.1 and will be based on Investigators' assessment.
Measure:Duration of response (DoR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Baseline up to 28 months
Safety Issue:
Description:DoR will be calculated for participants who have a best overall response of CR or PR and will be defined as the time from first occurrence of a documented OR until the time of documented disease progression or death (death within 30 days from last study treatment) from any cause, whichever occurs first. Censoring
Measure:Progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Baseline up to 28 months
Safety Issue:
Description:PFS will be defined as the time from first dose of cibisatamab or RO7122290 (C1D1) to the first occurrence of documented disease progression (based on RECIST Version 1.1 Investigator's assessment) or death from any cause, whichever occurs first. For participants who do not have documented progressive disease or death (within 30 days from last study treatment) during the study, PFS will be censored at the day of the last tumor assessment. Participants without any post-baseline assessments or with all post-baseline assessments having unknown result/response but known to be alive at the clinical cut off for the analysis will be censored at the date of study treatment initiation plus one day.
Measure:Change on CEACAM5 tumor expression levels
Time Frame:Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)
Safety Issue:
Description:Mandatory for the 4th-12th participant of each dose level
Measure:Change on CEA tumor expression levels
Time Frame:Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)
Safety Issue:
Description:Mandatory for the 4th-12th participant of each dose level
Measure:Change on FAP tumor expression levels
Time Frame:Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)
Safety Issue:
Description:Mandatory for the 4th-12th participant of each dose level
Measure:Change on 4-1BB tumor expression levels
Time Frame:Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)
Safety Issue:
Description:Mandatory for the 4th-12th participant of each dose level

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Trial Keywords

  • Microsatellite stable;
  • Metastatic colorectal cancer

Last Updated

August 5, 2021