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Completed

NCT Number: NCT04826003

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

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

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Key information

Conditions

Metastatic Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Rigshospitalet, København Ø, Denmark

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

RO7122290

Drug

RO7122290 will be administered using a QW (Part I) or Q3W (Part I or Part II) schedule in combination with 100 mg cibisatamab Q3W with obinutuzumab pre-treatment. The maximum dose of RO7122290 to be explored in combination with cibisatamab with obinutuzumab pre-treatment in this study is 500 mg for the QW dosing interval (Part I) or 1500 mg for the Q3W dosing interval (Part I or Part II).

Cibisatamab

Drug

Cibisatamab will be administered to participants at a fixed dose of 100 mg Q3W (100 mg on Day 1 of each 21-day cycle).

Obinutuzumab

Drug

Obinutuzumab will be administered (IV) as pre-treatment on Day - 8/- 7 (split dose) or

  • 8 (single dose) prior to C1D1 of cibisatamab and as re-treatment every 6 months if the participant is still receiving cibisatamab

Primary outcomes

  1. Part I: Occurrence of dose-limiting toxicities

    Time frame: Baseline up to 21 days

    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.

  2. Percentage of Participants with Adverse Events

    Time frame: Baseline up to 28 months

    Incidence, nature, and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 with the exception of cytokine release syndrome (CRS), which is graded according to the ASTCT grading scale for CRS (with individual signs and symptoms of CRS graded separately using the CTCAE v5.0 grading scale)

Secondary outcomes

  1. Serum concentration of RO7122290 over time

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  2. Plasma concentration of RO7122290 over time

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  3. Maximum concentration (Cmax) of RO7122290

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  4. Time of maximum concentration (Tmax) of RO7122290

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  5. Clearance (CL) of RO7122290

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  6. Volume of distribution (V) of RO7122290

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  7. Area under the curve (AUC) of RO7122290

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  8. Half-life (t1/2) of RO7122290

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  9. Serum concentration of Cibisatamab over time

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  10. Plasma concentration of Cibisatamab over time

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  11. Maximum concentration (Cmax) of Cibisatamab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  12. Time of maximum concentration (Tmax) of Cibisatamab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  13. Clearance (CL) of Cibisatamab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  14. Volume of distribution (V) of Cibisatamab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  15. Area under the curve (AUC) of Cibisatamab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  16. Half-life (t1/2) of Cibisatamab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  17. Serum concentration of Obinutuzumab over time

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  18. Plasma concentration of Obinutuzumab over time

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  19. Maximum concentration (Cmax) of Obinutuzumab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  20. Time of maximum concentration (Tmax) of Obinutuzumab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  21. Clearance (CL) of Obinutuzumab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  22. Volume of distribution (V) of Obinutuzumab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  23. Area under the curve (AUC) of Obinutuzumab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  24. Half-life (t1/2) of Obinutuzumab

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  25. 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)

    Cycle 1: Day 1, 8, 15; Cycles 3, 4, 6, 8: Day 1; Discontinuation visit. Each cycle is 21 days

  26. 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)

    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

  27. 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)

    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

  28. Treatment-induced change on T-cell proliferation (CD8/Ki67)

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  29. Treatment-induced change on T-cell activation (CD8/4-1BB)

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  30. Treatment-induced change on tumor necrosis factor alpha (TNF-alpha) levels

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  31. Treatment-induced change on interferon gamma (IFN-gamma) levels

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  32. Treatment-induced change on Interleukin (IL)-2 levels

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  33. Treatment-induced change on Interleukin (IL)-6 levels

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  34. Treatment-induced change on Interleukin (IL)-8 levels

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  35. Treatment-induced change on Interleukin (IL)-10 levels

    Time frame: Baseline up to 28 months (detailed time frame provided in 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

  36. 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)

    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

  37. 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

    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.

  38. 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

    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.

  39. Duration of response (DoR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Time frame: Baseline up to 28 months

    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

  40. Progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Time frame: Baseline up to 28 months

    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.

  41. Change on CEACAM5 tumor expression levels

    Time frame: Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)

    Mandatory for the 4th-12th participant of each dose level

  42. Change on CEA tumor expression levels

    Time frame: Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)

    Mandatory for the 4th-12th participant of each dose level

  43. Change on FAP tumor expression levels

    Time frame: Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)

    Mandatory for the 4th-12th participant of each dose level

  44. Change on 4-1BB tumor expression levels

    Time frame: Baseline, Cycle 2 Day 2, Discontinuation visit (up to 28 months)

    Mandatory for the 4th-12th participant of each dose level

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Apr 1, 2021
Registry last updated
Jul 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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