A Study of RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: RO7172508; Obinutuzumab; Tocilizumab
Intervention description: RO7172508 was administered at a dose and as per the schedule specified in the respective arms.; In the event obinutuzumab treatment is implemented, obinutuzumab will be administered either on Day-7 or on Day-7 and Day-6. If obinutuzumab is given only on one day, then the schedule for Day-7 should be followed including an end of infusion sample.; Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)
Intervention MeSH terms: Obinutuzumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study was to determine the maximum-tolerated dose (MTD) and/or the optimal biological
      dose (OBD) as well as the optimal schedule for intravenous (IV) and subcutaneous (SC)
      administrations of RO7172508 as monotherapy, with or without obinutuzumab pre-treatment, in
      participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA)-positive
      solid tumors who have progressed on standard of care (SOC) treatment, are intolerant to SOC,
      and/or are non-amenable to SOC. This study was conducted in two parts. Part I of the study
      consisted of an IV single participant cohort/multiple-ascending dose-escalation to evaluate
      the safety of RO7172508. Part II was a multiple participant cohort/multiple-ascending
      dose-escalation to define the MTD and/or OBD of RO7172508 administered as single agent, IV
      and/or SC, in participants with tumors that are expressing high as well as moderate/low-CEA.
      The study switched from Part I to Part II when the maximum planned dose for Part I was
      reached or the occurrence of a RO7172508-related Grade >= 2 adverse event (AE) or
      dose-limiting toxicity (DLT) was observed, whichever comes first. The Sponsor may decide to
      switch from Part I to Part II in the absence of an observed RO7172508-related Grade >= 2
      toxicity or prior to maximum planned dose for Part I.
    

Eligibility criteria:

        Inclusion Criteria:

          -  For Part I: participants with locally advanced and/or metastatic solid tumor with
             confirmed cytoplasmic and/or membranous high CEA expression in tumor tissue is
             required. Participants must have progressed on a SOC therapy, be intolerant to SOC,
             and/or are non-amenable to SOC.

          -  For <12 mg dose cohorts, serum CEA levels below a certain threshold is required as
             follows:

               -  For dose cohorts 65-159 microgram, a sCEA level of < 22 ng/mL

               -  For dose cohorts 160-399 microgram, a sCEA level of < 28 ng/mL

               -  For dose cohorts 400-799 microgram, a sCEA level of < 44 ng/mL

               -  For dose cohorts 800-1599 microgram, a sCEA level of < 70 ng/mL

               -  For the dose cohort of 1.6-3.1 milligram, a sCEA level of < 123 ng/mL

               -  For the dose cohort of 3.2-6.3 milligram, an sCEA level of < 229 ng/mL.

               -  For the dose cohort of 6.4-11.9 milligram, an sCEA level of < 440 ng/mL. If dose
                  fractionation is implemented, the sCEA threshold for inclusion should correspond
                  to the dose range of the first dose administered.

          -  For Part II, participants with locally advanced and/or metastatic solid tumor
             expressing cytoplasmic and/or membranous high-CEA or moderate/low-CEA on archival
             material, who have progressed on a SOC therapy, are intolerant to SOC, and/or are
             non-amenable to SOC. Participants must have a lesion amenable to biopsy (except
             participants with NSCLC, which may be enrolled with archival tissue available only).
             For participants with colorectal cancer (CRC) only, the CEA assessment by
             immunohistochemistry should be performed but the result is not required to enroll the
             participant.

          -  Radiologically measurable disease according to RECIST v1.1.

          -  Life expectancy of >= 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.

          -  All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure
             must have resolved to Grade <= 1 or returned to baseline except alopecia (any grade)
             and Grade 2 peripheral neuropathy.

          -  Adequate hematological, liver, renal, and lung function

          -  For women: agree to remain abstinent or use two contraceptive methods that result in a
             failure rate of <1% per year from screening until 2 months after the last dose of
             RO7172508 and have a negative pregnancy test within one week prior to the first study
             treatment administration

          -  For men: remain abstinent or use contraceptive measures such as a condom plus an
             additional contraceptive method that together result in a failure rate of <1% per
             year, with partners who are woman of childbearing potential and refrain from donating
             sperm during the study

        Exclusion Criteria:

          -  History or clinical evidence of central nervous system (CNS) primary tumors or
             metastases unless they have been previously treated, are asymptomatic, and have had no
             requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days before
             screening.

          -  Non-irradiated lesions > 2 cm at critical sites where tumor swelling induced by
             RO7172508 is expected to lead to significant complications.

          -  Another invasive malignancy in the last 2 years

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results or contraindicate the use of
             an investigational drug.

          -  Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac
             arrhythmia that requires treatment with the exceptions of atrial fibrillation and
             paroxysmal supraventricular tachycardia, and history of myocardial infarction within 6
             months of enrollment.

          -  Active or uncontrolled infections.

          -  Known hepatitis B or C

          -  Major surgery or significant traumatic injury < 28 days prior to the first RO7172508
             administration or anticipation of the need for major surgery during study treatment.

        Specific Exclusion Criteria if Pre-treatment with Obinutuzumab is Implemented:

          -  Known HIV

          -  Positive test results for HBV infection, HBcAb indicating an active viral infection
             and positive test results for HCV.

          -  Participants positive for HCV antibody are eligible only if polymerase chain reaction
             (PCR) is negative for HCV ribonucleic acid (RNA).

          -  History of progressive multifocal leukoencephalopathy.

          -  Active TB requiring treatment within 3 years prior to baseline.

          -  Latent TB diagnosed during Screening.

          -  Positive test results for human T-lymphotropic virus 1