A Study of RO6958688 in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen Positive Solid Tumors

Not Recruiting

Trial ID: NCT02324257


Study BP29541 is a first-in-human, open-label, multi-center, dose-escalation Phase I clinical study of single-agent RO6958688 in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA) positive solid tumors who have progressed on standard treatment, are intolerant to standard of care (SOC), and/or are non-amenable to SOC. The study will be conducted in two parts. Part I of the study will investigate the safety and pharmacokinetics of a single dose of RO6958688 in single participant cohorts with dosing starting from a minimal anticipated biological effect level dose of 0.05 milligrams (mg) and up to a maximum dose of 2.5 mg. Part II will establish the appropriate therapeutic dose based on safety, pharmacokinetics, and the maximum tolerated dose (MTD) of RO6958688 for the once per week (QW) regimen, every three weeks (Q3W) regimen, and for the step up dosing regimen.

Official Title

An Open-Label, Multicenter, Dose-Escalation Phase I Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688, A Novel T-cell Bispecific Antibody That Targets the Human Carcinoembryonic Antigen (CEA) on Tumor Cells and CD3 on T Cells, Administered Intravenously in Patients With Locally Advanced and/or Metastatic CEA(+) Solid Tumors

Stanford Investigator(s)

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine

Tyler Johnson
Tyler Johnson

Clinical Assistant Professor, Medicine - Oncology

Hans-Christoph Becker, MD, FSABI, FSCCT

Clinical Professor, Radiology


Inclusion Criteria:

   - For dose escalation, locally advanced and/or metastatic gastrointestinal (GI) solid
   tumor in participants who have progressed on a standard therapy, are intolerant to
   SOC, and/or are non-amenable to SOC and other solid tumors expressing CEA. Only
   locally advanced and/or metastatic colorectal cancer participants should be included
   in the scheduled comparison expansion

   - Radiologically measurable disease according to RECIST v1.1

   - Life expectancy, in the opinion of the investigator of greater than or equal (>/=) to
   12 weeks and LDH= 2.5 x ULN

   - Eastern Cooperative Oncology Group Performance Status of 0-1

   - All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure
   must have resolved to Grade less than or equal to 1 or returned to baseline except
   alopecia (any grade) and Grade 2 peripheral neuropathy

   - Adequate hematological, liver, and renal function

   - Participants must agree to remain abstinent or be willing to use effective methods of
   contraception as defined in the protocol

   - Non-GI solid tumors (like non-small cell lung cancer or breast cancer) should have
   confirmed CEA expression in tumor tissue >/= 20% of tumor cells staining with at least
   moderate to high intensity of CEA expression are required (immunohistochemistry
   [IHC]2+ and IHC 3+). For CRC, pancreatic and gastric cancer participants, the CEA
   assessment will be performed retrospectively and the result is not needed to enroll
   the participant

Exclusion Criteria:

   - Participants with a history or clinical evidence of central nervous system primary
   tumors or metastases including leptomeningeal 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

   - 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 at least 2 weeks prior to enrollment

   - Leptomeningeal disease

   - Participants with paraspinal, paratracheal and mediastinal pathologic lesions larger
   than 2 centimeters unless they are previously irradiated. Irradiation of lesions must
   be completed at least 14 days prior to initiation of study treatment

   - Participants with another invasive malignancy in the last 2 years (with the exception
   of basal cell carcinoma and tumors deemed by the investigator to be of low likelihood
   for recurrence)

   - 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, including diabetes mellitus, history of relevant
   cardio-pulmonary disorders, and known autoimmune diseases

   - Participants with bilateral lung lesions and dyspnea and/or with bilateral lung
   lesions and an oxygen saturation (SaO2) level less than 92% or participants with
   lobectomy or pneumonectomy with lung metastases in the remaining lung and either
   dyspnea or SaO2 less than 92% at baseline

   - Uncontrolled hypertension (systolic blood pressure [BP] greater than [>] 150
   millimeters of mercury [mmHg] and/or diastolic BP > 100 mmHg), unstable angina,
   congestive heart failure of any New York Heart Association classification, 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 human immunodeficiency virus (HIV) or known active hepatitis B or hepatitis C
   infection for participants not receiving obinutuzumab pretreatment

   - Known HIV (HIV testing will be performed at screening if required by local
   regulations) in participants to be pretreated with obinutuzumab

   - Pregnant or breastfeeding women

   - Known hypersensitivity to any of the components of RO6958688 and/or obinutuzumab

   - Concurrent therapy with any other investigational drug

   - Last dose of any chemotherapy less than 28 days prior to the first RO6958688 infusion

   - Expected need for regular immunosuppressive therapy

   - Regular dose of corticosteroids the 28 days prior to Day 1 of this study or
   anticipated need for corticosteroids that exceeds prednisone 10 mg/day or equivalent
   within 28 days prior to the first RO6958688 infusion. Inhaled and topical steroids are

   - Radiotherapy within the last 28 days prior to the first RO6958688 infusion with the
   exception of limited-field palliative radiotherapy.

Additional Exclusion Criteria for Participants to be Pretreated with Obinutuzumab:

   - Positive test results for human T-lymphotropic virus 1 (HTLV-1) or active HIV

   - Positive test results for chronic hepatitis B infection or hepatitis C

   - Known active tuberculosis (TB) requiring treatment within 3 years prior to baseline or
   latent TB that has not been appropriately treated

   - Active bacterial, viral, fungal, or other infection, or any major episode of infection
   requiring treatment with intravenous (IV) antibiotics within 4 weeks of Cycle 1, Day 1

   - Known hypersensitivity to any of the components of obinutuzumab; hypersensitivity to
   Chinese hamster ovary cell products or other recombinant human antibodies

   - History of progressive multifocal leukoencephalopathy (PML)


drug: RO6958688

drug: Obinutuzumab

drug: Tocilizumab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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