Solid tumors Cancer
Conditions
Interventions
Part IA: selicrelumab (IV) + atezolizumab
Selicrelumab at a dose of 16 mg was administered intravenously (IV) on Day 1 of Cycle 1 (the first cycle in this group was 42 days, with subse
and atezolizumab 1200 mg was administered IV after 6 weeks on Day 1 of Cycle 2, followed by every 3 weeks during Part IA until disease progression, death, loss of follow-up, or withdrawal of consent.
and atezolizumab 1200 mg was administered IV on Day 1 of Cycle 2, and followed by every 3 weeks during Part IA as long as the participant experiences clinical benefit in the opinion of the investigato
and atezolizumab 1200 mg was administered IV on Day 1 of Cycle 1, and followed by every 3 weeks during Part IB as long as the participant experienced clinical benefit in the opinion of the investigato
and selicrelumab was administered at the dose defined in Part IB (not exceeding 80 mg SC [unless IV administration in Part IB demonstrates better benefit/risk ratio]) on Day 2 (1 day after atezolizuma
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors, which are not amenable to standard therapy: Part I: histologically confirmed diagnosis of advanced/metastatic small and large bowel carcinomas (small bowel and CRC), CPI-experienced non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) Part II: CPI-experienced NSCLC patients must have experienced documented disease progression on or after PD-L1 or PD-1 inhibitor therapy (investigational or approved): screening tumor assessment should confirm prior progression 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 3. Life expectancy greater than or equal to 16 weeks 4. Adequate hematologic and end organ function 5. Measurable disease per RECIST Version 1.1 6. Ability to comply with the protocol requirements 7. Female participants of childbearing potential must have a negative pregnancy test (urine/serum) within seven days prior to the first study drug administration 8. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than (<) 1% per year during the treatment period and for at least 5 months after the last dose of study treatment 9. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 28 days after the last dose of study treatment
Exclusion criteria
Exclusion criteria: 1. If one of the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1 Day 1) are: soluble interleukin 2 receptor (sCD25) greater than (>) 2 × upper limit of normal (ULN); Serum ferritin >1000 ng/ml 2. Any approved anti-cancer therapy that includes chemotherapy, hormonal therapy, or radiotherapy within 2 weeks prior to the first dose of study treatment; the following is, however, allowed: Palliative radiotherapy for bone metastases less than or equal to (</=) 2 weeks prior to Cycle 1 Day 1 3. Adverse events from prior anti-cancer therapy that have not resolved to Grade </= 1 except for any grade alopecia and </= Grade 2 peripheral neuropathy 4. Bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (example: bone metastasis or osteoporosis) is allowed 5. Uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent drainage procedures (one monthly or more frequently). Participants with indwelling catheters are allowed 6. Known clinically significant liver disease which includes active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease 7. History (within the previous year) of congestive heart failure, stroke, arrhythmia, or myocardial infarction 8. History of peripheral venous thrombosis or thromboembolic event (within 12 months prior to Cycle 1 Day 1) 9. Significant cardio- or cerebrovascular disease within 6 months prior to Cycle 1 Day 1 10. Known hereditary or acquired coagulopathies 11. Clinically meaningful proteinuria 12. Requiring dialysis (peritoneal or hemodialysis) 13. Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS metastases: participants with asymptomatic-treated CNS metastases may be enrolled after consultation with the Medical Monitor, provided they meet the following criteria: 13.1. Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study 13.2. No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1 Day 1 14. Pregnancy, lactation, or breastfeeding 15. Allergy or hypersensitivity to components of the RO7009789 formulation or to components of atezolizumab formulation 16. History of autoimmune diseases (participants with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible; participants with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study) 17. History of idiopathic pulmonary fibrosis, pneumonitis (excluding infectious disease-induced), organizing pneumonia, or evidence of active pneumonitis 18. History of radiation pneumonitis in the radiation field (fibrosis) is permitted 19. Participants with human immunodeficiency virus (HIV) infection, active hepatitis B (chronic or acute), or hepatitis C infection 20. Active tuberculosis 21. Severe infections within 4 weeks prior to Cycle 1 Day 1 22. Sig
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part IA: Percentage of participants with adverse events and serious adverse events, classified according to the NCI CTCAE v4.0 toxicity grade, measured from baseline up to 28 days after the last dose (approximately 60 months) Part IB: 1. Percentage of participants with adverse events and serious adverse events, classified according to the NCI CTCAE v4.0 toxicity grade, measured from baseline up to 28 days after the last dose (approximately 60 months) 2. Percentage of participants with dose-limiting toxicities (DLTs), measured using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) from Cycle 1 Day 1 up to Cycle 2 Day 2 (cycle length = 21 days) 3. Maximum tolerated dose (MTD) of selicrelumab, measured using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) from Cycle 1 Day 1 up to Cycle 2 Day 2 (cycle length = 21 days) 4. Recommended Part II dose of selicrelumab calculated from the MTD, measured from Cycle 1 Day 1 up to Cycle 2 Day 2 (cycle length = 21 days) Part II: 1. Percentage of participants with adverse events and serious adverse events, classified according to the NCI CTCAE v4.0 toxicity grade, measured from baseline up to 28 days after the last dose (approximately 60 months) 2. Percentage of participants with best overall response, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 from baseline up to disease progression (PD) or death due to any cause, whichever occurs first (up to approximately 60 months) 3. Progression-free survival (PFS), as determined by the investigator using RECIST Version 1.1 from baseline up to PD or death due to any cause, whichever occurs first (up to approximately 60 months) 4. Duration | — |
Secondary
| Measure | Time frame |
|---|---|
| Part IA: 1. Area under the concentration time curve (AUC) of selicrelumab measured from serum samples taken at pre selicrelumab dose (1 h) on Cycle (Cy) 1 Day 1 (D1); 4, 8, 24, 48, 72 h post D1 dose; D8, 15 of Cy 1; D1 Cy 2&3 (10 minutes pre ATZ dose); at radiographic disease progression (PD) (up to 60 months); 28 & 150 days after last ATZ dose (up to 60 months) (Cy = 21days) 2. Maximum serum concentration (Cmax) of selicrelumab, measured from serum samples taken at pre selicrelumab dose (within 1 h) on Cy 1 D1; 4, 8, 24, 48, 72 h post D1 dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 minutes [min] pre ATZ dose); at radiographic PD (up to 60 months); 28 & 150 days after last ATZ dose (up to 60 months) (Cy = 21days) 3. Time to Cmax (Tmax) of selicrelumab, measured from serum samples taken at pre selicrelumab dose (within 1 h) on Cy 1 D1; 4, 8, 24, 48, 72 h post D1 dose; D8, D15 of Cy 1; D1 of Cy 2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 60 months); 28 & 150 days after last ATZ dose (up to 60 months) (Cy = 21days) 4. Minimum serum concentration under steady-state (Cmin) of selicrelumab, measured from serum samples taken at pre selicrelumab dose (within 1 h) on Cy1 D1; 4, 8, 24, 48, 72 h post D1 dose; D8, D15 of Cy1; D1 of Cy 2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 60 months); 28 & 150 days after last ATZ dose (up to 60 months) (Cy = 21days) 5. Apparent clearance (CL/F) of selicrelumab, measured from serum samples taken at pre selicrelumab dose (within 1 h) on Cy1 D1; 4, 8, 24, 48,72 h post D1dose; D8, D15 of Cy1; D1 of Cy 2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 60 months); 28 & 150 days after last ATZ dose (up to 60 months) (Cy = 21 days) All other endpoints measured using serum samples (as applicable): 6. Half-life (t1/2) of selicrelumab, measured pre selicrelumab dose (within 1 h) on Cy1 D1; 4, 8, 24, 48,72 h post D1 do | — |
Countries
Canada, Denmark, France, Netherlands, Spain, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed