Solid tumors Cancer
Conditions
Interventions
The study will be conducted in two parts. Part I of the study will investigate the safety and pharmacokinetics of a single dose of cibisatamab in single participant cohorts with dosing starting from a
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. Radiologically measurable disease according to RECIST v1.1 3. Life expectancy, in the opinion of the investigator of greater than or equal (>/=) to 12 weeks and LDH= 2.5 x ULN 4. Eastern Cooperative Oncology Group Performance Status of 0-1 5. 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 6. Adequate hematological, liver, and renal function 7. Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol 8. 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
Exclusion criteria: 1. 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 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 at least 2 weeks prior to enrollment 3. Leptomeningeal disease 4. 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 5. 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) 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 cardio-pulmonary disorders, and known autoimmune diseases 7. 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 8. 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 9. Active or uncontrolled infections 10. Known human immunodeficiency virus (HIV) or known active hepatitis B or hepatitis C infection for participants not receiving obinutuzumab pretreatment 11. Known HIV (HIV testing will be performed at screening if required by local regulations) in participants to be pretreated with obinutuzumab 12. Pregnant or breastfeeding women 13. Known hypersensitivity to any of the components of cibisatamab and/or obinutuzumab 14. Concurrent therapy with any other investigational drug 15. Last dose of any chemotherapy less than 28 days prior to the first cibisatamab infusion 16. Expected need for regular immunosuppressive therapy 17. 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 cibisatamab infusion. Inhaled and topical steroids are permitted 18. Radiotherapy within the last 28 days prior to the first cibisatamab infusion with the exception of limited-field palliative radiotherapy. 19. Additional Exclusion Criteria for Participants to be Pretreated with Obinutuz
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of participants with adverse events (AEs) or serious adverse events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 (NCI CTCAE v5 was used for CRS) at baseline up to 60 months 2. Percentage of participants with dose-limiting toxicities (DLTs) measured using NCI CTCAE v4.03 (NCI CTCAE v5 was used for CRS) at Day 1 up to Day 21 3. Percentage of participants with anti-drug antibodies (ADAs) against cibisatamab measured using an ADA assay at pre-dose (Hour 0) on Cycle 1 Day 1 up to 60 months (detailed timeframe is provided in the outcome description section)] Part I: Pre-dose (Hour 0) on Day 1 of Cycles 1, 2-3; 120 hours after the end of infusion (EOI) in Cycle 1. Part II QW: pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4. Part II Q3W: pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4; 120 hours and 336 hours after EOI in Cycle 1, and 120 hours after EOI in Cycles 2, 3, 4. For Part I and II (QW and Q3W): pre-dose (Hour 0) on Day 1 of every cycle after Cycle 4 (Cycle 3 for Part I) up to treatment discontinuation (approximately 60 months), 28 days after last dose (approximately 60 months) (Cycle = 7 days for Part I and II QW; 21 days for Part II Q3W) (infusion duration = 30 minutes for Part I and 120 minutes for Part II [QW and Q3W]) 4. MTD of cibisatamab with/without obinutuzumab pretreatment measured using NCI CTCAE v4.03 (NCI CTCAE v5 was used for CRS) at Day 1 up to Day 21 5. Late cycle MTD of cibisatamab without obinutuzumab pretreatment for the step-up dosing regimen measured using NCI CTCAE v4.03 (NCI CTCAE v5 was used for CRS) at Day 1 up to Day 7 of each cycle as long as the dose is escalated weekly in Part II QW (up to approximately 60 months; Cycle = 7 days)]. Late cycle MTD is defined as the highest dose with less than or equal to DLT having been observed for 6 evaluable participants. If more than 6 parti | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Percentage of participants with an objective response of complete response (CR) or partial response (PR) measured using Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 at baseline up to 60 months (detailed timeframe is provided in the outcome description section)] Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) 2. Duration of response (DOR) measured using RECIST v1.1 at baseline up to 60 months (detailed timeframe is provided in the outcome description section)] Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) 3. Percentage of participants with stable disease (SD) measured using RECIST v1.1 at baseline up to 60 months (detailed timeframe is provided in the outcome description section)] Baseline up to 60 months (assessed at Screening, at 12 weeks [in Part I], at 8 weeks [in Part II QW and Q3W] after Cycle 1 Day 1, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death whichever occurs first, up to 60 months) (Cycle = 7 days for Part I and II QW, and 21 days for Part II Q3W) 4. Percentage of participants with disease control, defined as partial response + complete response + stable disease (PR+CR+SD), measured using RECIST v1.1 at baseline up to 60 months (detailed timeframe is provided in the outcome description section)] | — |
Countries
Canada, Denmark, Italy, Netherlands, Spain, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed