Solid tumors Cancer
Conditions
Interventions
Dose-Escalation (Part IA):
Participants will receive cibisatamab weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 we
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. Radiologically measurable and clinically evaluable disease (as per RECIST v1.1) 3. Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate dehydrogenase (LDH) levels </= 2.5 ULN (upper limit of normal) 4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 5. 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 6. Adequate hematological, liver, and renal function 7. Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </= 2 years after start of menopause (menopause is defined as amenorrhea for more than 2 years) 8. Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol 9. 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
Exclusion criteria: 1. 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 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 pathological lesions larger than 2 cm unless they are previously irradiated 5. 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 6. Significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results 7. Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious cardiac arrhythmia requiring treatment history of myocardial infarction within 6 months of enrollment 8. 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 9. Human Immunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV) 10. 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 11. Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1 12. 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 13. 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 treatment 14. Known history of autoimmune disease as defined in the protocol 15. 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 16. 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 17. Pregnant or breastfeeding 18. Known hypersensitivity to any of the components of cibisatamab and atezolizumab; hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies 19. 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-p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Number of participants with adverse events (AEs) 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. Maximum-tolerated dose (MTD) of cibisatamab in combination with atezolizumab measured using NCI CTCAE v4.03 (NCI CTCAE v5 was used for CRS) Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation 4. Recommended Phase II Dose (RP2D) of cibisatamab in combination with atezolizumab measured using NCI CTCAE v4.03 (NCI CTCAE v5 was used for CRS) at Day 1 up to 60 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetics (PK): area under the concentration-time curve (AUC) of cibisatamab measured using a validated bi-functional PK assay at baseline up to 60 months 2. PK: volume of distribution at steady state (Vss) of cibisatamab measured using a validated bi-functional PK assay at baseline up to 60 months 3. PK: maximum serum concentration (Cmax) of cibisatamab measured using a validated bi-functional PK assay at baseline up to 60 months 4. PK: clearance (CL) of cibisatamab measured using a validated bi-functional PK assay at baseline up to 60 months 5. Pharmacodynamics: immune cell numbers measured using immunohistochemistry (IHC), gene expression and fluorescence-activated cell sorting (FACS) at pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length = 21 days) 6. Percentage of participants with objective response (partial response [PR] or complete response [CR] measured using Response Evaluation Criteria in Solid Tumors [RECIST]) at baseline up to 60 months. Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation. 7. Percentage of participants with disease control (PR, CR or stable disease [SD]) measured using RECIST at baseline up to 60 months. Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation. 8. Percentage of participants with stable disease (SD) measured using RECIST at baseline up to 60 months. Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation. 9. Duration of response (DOR) measured using RECIST from initial object | — |
Countries
Canada, Denmark, France, Italy, Netherlands, Spain, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed