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

Completed

Conditions: solide tumoren
Cancer
solid tumors

Registration Number: NL-OMON46944

Lead Sponsor: Roche Nederland B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

* For dose escalation, locally advanced and/or metastatic gastrointestinal solid tumor in patients who have progressed on a standard therapy, are intolerant to SOC, and/or are non-amenable to SOC and other solid tumors expressing CEA as per inclusion criterion 14.
* Radiologically measurable disease according to RECIST v1.1
* Life expectancy (in the opinion of the investigator) of ><= 12 weeks and lactate dehydrogenase levels <<= 2.5 upper limit of normal
* Eastern Cooperative Oncology Group 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 and renal function
* Patients must agree to be willing to use effective methods of contraception as defined in the protocol
* Non-gastrointestinal solid tumors (like non-small cell lung cancer or breast cancer patients) 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 IHC3+). For CRC patients only, the CEA assessment should be performed but the result is not required to enroll the patient.
* For the biomarker cohort, only patients with moderate/low CEA expression and very low/negative CEA expression or IHCO+ will be enrolled. CEA expression should be determined prior to enrollment.

Exclusion Criteria

1.Active or untreated central nervous system (CNS) metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments
2. 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 enrollment.
3. Leptomeningeal disease.
4. patients with paraspinal, paratracheal and mediastinal pathological lesions larger than 2 cm inless they are previously irridiated.
5. Patients 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)
6. 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 pulmonary disorders, and known autoimmune diseases
7. Patients with bilateral lung lesions and dyspnea and/or with bilateral lung lesions and SaO2 < 92% (at rest, room air) or patients with lobectomy or pneumonectomy with lung metastases in the remaining lung and either dyspnea or SaO2 less than 92% (at rest, room air) at baseline

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>* To assess the safety profile of RO6958688 with/without obinutuzumab<br /><br>pretreatment<br /><br>* To determine the maximum-tolerated dose (MTD) and/or the recommended dose and<br /><br>schedule (optionally with obinutuzumab pretreatment) for further development<br /><br>* To determine the late cycle maximum tolerated dose (late<br /><br>cycle MTD)<br /><br>* To establish the pharmacokinetics of RO6958688 as monotherapy with/without<br /><br>obinutuzumab pretreatment<br /><br>* To assess the effect of obinutuzumab pretreatment in decreasing the rate of<br /><br>patients with positive Anti-Drug Antibodies (ADA) titer against RO6958688 at<br /><br>week 8 and/or delaying the time of onset of ADA against RO6958688<br /><br></p><br>

Secondary Outcome Measures