A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors

Not Recruiting

Trial ID: NCT02650713


This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab. Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.

Official Title

An Open-Label, Multicenter, Dose Escalation and Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Patients With Locally Advanced and/or Metastatic CEA-Positive 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 Associate Professor, Medicine - Oncology


Inclusion Criteria

   - Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor
   lesion of accessible non-critical location to biopsy, in participants who have
   progressed on a standard therapy, are intolerant to standard therapy, and/or are
   non-amenable to standard therapy

   - Radiologically measurable and clinically evaluable disease (as per RECIST v1.1)

   - Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate
   dehydrogenase (LDH) levels
   - 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    and Grade 2 peripheral neuropathy

   - Adequate hematological, liver, and renal function

   - Negative serum pregnancy test within 7 days prior to study treatment in premenopausal
   women and women    amenorrhea for more than 2 years)

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

   - Participants with non-colorectal cancer should have confirmed CEA expression in tumor
   tissue. For colorectal cancer (CRC), the CEA assessment should be performed but the
   result is not required for participant selection

Exclusion Criteria

   - Active or untreated central nervous system (CNS) metastases as determined by computed
   tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and
   prior radiographic assessments

   - 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 pathological lesions
   larger than 2 cm unless they are previously irradiated

   - Malignancies within 5 years prior to enrollment, with the exception of those with a
   negligible risk of metastasis or death and treated with expected curative outcome

   - Significant, uncontrolled concomitant diseases which could affect compliance with the
   protocol or interpretation of results

   - Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious
   cardiac arrhythmia requiring treatment history of myocardial infarction within 6
   months of enrollment

   - Administration of a live, attenuated vaccine within 28 days before Cycle 1 Day 1 or
   anticipation that such a live attenuated vaccine will be required during the study

   - Human Inmmunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV)

   - Severe infections within 28 days prior to Cycle 1 Day 1, including but not limited to
   hospitalization for complications of infection, bacteremia, or severe pneumonia or
   active tuberculosis

   - Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1

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

   - Major surgery or significant traumatic injury less than 28 days prior to Cycle 1 Day 1
   (excluding biopsies) or anticipation of the need for major surgery during study

   - Known history of autoimmune disease as defined in the protocol

   - History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
   organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
   pneumonia, etc.), or evidence of active pneumonitis (including drug induced) on
   screening chest CT scan. History of radiation pneumonitis in the radiation field
   (fibrosis) is permitted

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

   - Pregnant or breast-feeding

   - Known hypersensitivity to any of the components of RO6958688 and atezolizumab;
   hypersensitivity to Chinese hamster ovary cell products or other recombinant human

   - Investigational therapy (defined as treatment for which there is no regulatory
   authority approved indication) or last dose of prior immunotherapies within 28 days
   prior to Cycle 1 Day 1. Participants previously treated with anti-programmed
   death-ligand 1 (PD-L1), or anti-PD-1 are excluded

   - Last dose of any approved anti-cancer therapy within 28 days prior to the first
   RO6958688 infusion

   - Prior systemic corticosteroids greater than 10mg prednisone (or equivalent) within 14
   days of Cycle 1 Day 1. Inhaled and/or topical steroids are permitted

   - Expected need for regular immunosuppressive therapy

   - Radiotherapy within the last 28 days before Cycle 1 Day 1 with the exception of
   limited-field palliative radiotherapy


drug: RO6958688

drug: RO6958688

drug: Atezolizumab

Not Recruiting

Contact Information

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

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