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
- Conditions
- solide tumorenCancersolid tumors
- Registration Number
- NL-OMON47345
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
- Age * 18 years
- Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in patients 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 - previously irradiated lesions should not be counted as target lesions)
- Life expectancy of * 12 weeks and LDH levels <=<2.5 ULN
- 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 haematological, liver and renal function
- Patients with non-colorectal cancer should have confirmed CEA expression in tumor or centrally confirmed CEA expression in tumor tissue. For CRC cancer patients, the CEA assessment should be performed, but result is not required for patient selection. If no archival tumor tissue is available, in this case fresh biopsy is collected.
- Active or untreated central nervous system (CNS) metastases as determined by CT or 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 * 2 weeks prior to enrolment
- Leptomeningeal disease
- Patients 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
- 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
- Known history of autoimmune disease
- patients with bilateral lung lesions and dyspnea and/or SaO2<92% or patients with lobectomy or pneumonectomy with lung metastases in the remaining lung and either dyspnea or SaO2 <92% at baseline.
- Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 28 days prior to Cycle 1 Day 1
- Regular immunosuppressive therapy
- Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
- Radiotherapy within the last 28 days before Cycle 1 Day 1 with the exception of limited field palliative radiotherapy for bone pain relief
See protocol for Obinutuzumab-specific exclusion criteria.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety outcome measures<br /><br>The safety outcome measures for this study are:<br /><br>* Incidence and nature of DLTs<br /><br>* Incidence and severity of adverse events and IRRs and cytokine-release<br /><br>syndrome symptoms<br /><br>* Incidence of laboratory abnormalities (hematology testing, coagulation, serum<br /><br>chemistries, and urinalysis)<br /><br>* Incidence of ADAs (anti-atezolizumab antibodies and anti-RO6958688 antibodies)<br /><br>formation, detection of cytokine release and potential correlation with PK, PD,<br /><br>safety,<br /><br>and efficacy parameters<br /><br>* Incidence of autoantibodies (anti-nuclear antibody, anti-double-stranded DNA,<br /><br>cytoplasmic anti-neutrophil cytoplasmic antibody, and perinuclear<br /><br>anti-neutrophil<br /><br>cytoplasmic antibody) in comparison to baseline<br /><br>* Changes in vital signs, physical findings and ECG findings.</p><br>
- Secondary Outcome Measures
Name Time Method