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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000812-33 | EudraCT Number |
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This global, multicenter, open-label study will evaluate the safety and tolerability of atezolizumab in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The atezolizumab plus ipilimumab arm (Arm A) will focus primarily on participants with advanced or metastatic non-small cell lung cancer (NSCLC). The atezolizumab plus interferon alfa-2b arm (Arm B), plus pegylated interferon alfa-2a (PEG-interferon alfa-2a, Arm C), and atezolizumab plus PEG-interferon Alfa-2a plus bevacizumab (Arm D) will enroll participants with advanced or metastatic renal cell carcinoma (RCC), metastatic NSCLC and melanoma. The atezolizumab plus obinutuzumab) (Arm E) will enroll participants with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Atezolizumab will be administered as intravenous (IV) infusion every 3 weeks (q3w).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Atezolizumab with Ipilimumab | Experimental | Participants will receive atezolizumab along with ipilimumab. |
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| Arm B: Atezolizumab with Interferon alfa-2b | Experimental | Participants will receive atezolizumab along with Interferon alfa-2b. |
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| Arm C: Atezolizumab with PEG- interferon alfa-2a | Experimental | Participants will receive atezolizumab along with PEG- interferon alfa-2a. |
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| Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab | Experimental | Participants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab. |
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| Arm E: Atezolizumab with Obinutuzumab | Experimental | Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w. |
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| Measure | Description | Time Frame |
|---|---|---|
| Recommended Phase II Dose (RP2D) of Atezolizumab When Given in Combination With Ipilimumab and Interferon Alfa-2b | From the first atezolizumab treatment up to 21 days | |
| Percentage of Participants with Adverse Events | From the first atezolizumab treatment up to 4.5 years (yr) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Best Overall Response, as Assessed Using Conventional Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) | |
| Percentage of Participants with Best Overall Response, as Assessed Using Immune Modified RECIST Criteria |
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Inclusion Criteria:
Inclusion criteria specific to Arm A: Atezolizumab+ Ipilimumab
Inclusion criteria specific to Arm B: Atezolizumab+ Interferon alfa-2b
Inclusion Criteria Specific to Arm C (Atezolizumab plus PEG-Interferon Alafa-2a):
- Cohort 1: participants with RCC
Inclusion Criteria Specific to Arm D (Atezolizumab plus PEG-Interferon Alfa-2a +Bevacizumab)
Inclusion Criteria Specific to Arm E (Atezolizumab +Obinutuzumab)
- R/M HNSCC participants with at least one prior line of systemic therapy
Inclusion Criteria Specific to prior Anti-PD-L1/PD-1 Treated Cohorts:
Exclusion Criteria:
General Medical Exclusions:
Cancer-Specific Exclusions:
Exclusion Criteria Related to Medications:
Exclusion Criteria Specific to Interferon Alpha Therapy (Arms B-D):
Exclusion Criteria Specific to Bevacizumab (Arm D)
Exclusion Criteria Specific Obinutuzumab (Arm E)
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HonorHealth Research Institute - Bisgrove | Scottsdale | Arizona | 85258 | United States | ||
| Mayo Clinic- Scottsdale |
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| Bevacizumab | Drug | Participant will receive Bevacizumab 15 milligrams per kilograms (mg/kg) IV infusion q3w. |
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| Interferon alfa-2b | Drug | Participants will receive Interferon alfa-2b 3, 5, or 10 million international units subcutaneously every other day for up to 3 doses per week. |
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| Ipilimumab | Drug | Participants will receive Ipilimumab 1, or 3 mg/kg IV, single dose, or multiple-dose regimen q3w for up to 4 cycles (Cycle = 21 days). |
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| Obinutuzumab | Drug | Obinutuzumab 1000 milligrams will be administered as pre-treatment on 2 consecutive days (Day -13 and Day -12) prior to treatment start with atezolizumab on Cycle 1, Day 1 (cycle length=21 days). An additional two doses of obinutuzumab will be administered on Days 85 and 86 of study treatment (Cycle 5, Day 1 and Cycle 5, Day 2). |
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| PEG-interferon alfa-2a | Drug | Participant will receive PEG-interferon alfa-2a 180 micrograms subcutaneous injection q3w for a total of 6 cycles (Cycle = 21 days). |
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| Screening to progression or death, up to 4.5 years (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) |
| Duration of Objective Response | Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) |
| Overall Survival | Baseline to death (up to 4.5 yr) |
| Progression-Free Survival | Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) |
| Percentage of Participants with Objective Response, as Assessed Using Conventional RECIST v1.1 | Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) |
| Percentage of Participants with Objective Response, as Assessed Using Immune Modified RECIST Criteria | Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) |
| Serum Atezolizumab Concentration | Arm A: Predose (0 hour [hr]), 30 minutes (min) post end of infusion on Day 1;Day 8,Day 15 of Cycle (cy) 1;Predose (0 hr) on Day 1 of cy 2,3,4,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 years [yr]). Arm B: Predose (0 hr) on Day 1,30 min post end of infusion on Day 8,Day 15,Day 22 of cy 1;Predose (0 hr) on Day 1 of cy 2,3,4,5,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arms C,D: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,3;Predose (0 hr) on Day 1 of cy 2,4,8, every 8 cy thereafter up to end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arm E: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,5;Predose (0 hr) on Day 1 of cy 2,3,4,8, every 8 cy thereafter up to treatment end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length = 21 days (28 days for Arm B, cycle 1) | Baseline up to 4.5 years (detailed timeframe is given in outcome description) |
| Serum Ipilimumab Concentration | Predose (0 hr), 30 min post end of infusion on Day 1 of Cy 1,3;Predose on Day 1 of Cy 4; end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days | Baseline up to 4.5 years (detailed timeframe is given in outcome description) |
| Serum Bevacizumab Concentration | Predose (0 hr), 30 min post end of infusion on Day 1 of Cy 1,3; end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days | Baseline up to 4.5 years (detailed timeframe is given in outcome description) |
| Serum Obinutuzumab Concentration | Predose (0 hr), 30 min post end of infusion on Days -13, -12 and on Day 1 Cy 5; end of treatment/withdrawal;≥90 days post last dose (up to 4.5 yr) Cycle length = 21 days | Baseline up to 4.5 years (detailed outcome given in outcome description) |
| Anti-Drug Antibody to Atezolizumab | Detailed timeframe: Arm A: Predose (0 hr) on Day 1 of Cy 1,2,3,4,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arm B: Predose (0 hr) on Day 1 of Cy 1,2,3,4,5,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arms C, D, E: Predose (0 hr) on Day 1 of cy 1,2,3,4,8, thereafter every 8 Cy up to end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length = 21 days (28 days for Arm B, cycle 1) | Baseline up to 4.5 years (detailed timeframe is given in outcome description) |
| Anti-Drug Antibody to Ipilimumab | Pre-dose (0 hr) on Day 1 of Cy 1, 4, end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days | Baseline up to 4.5 years (detailed timeframe is given in outcome description) |
| Anti-Drug Antibody to Bevacizumab | Predose (0 hr) on Day 1 of Cy 1, 3; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length = 21 days | Baseline up to 4.5 years (detailed timeframe is given in outcome description) |
| Anti-Drug Antibody to Obinutuzumab | Predose (0 hr) on Days -13 and -12; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days | Baseline up to 4.5 years (detailed timeframe is given in outcome description) |
| Scottsdale |
| Arizona |
| 85259 |
| United States |
| UCLA | Los Angeles | California | 90095 | United States |
| Yale University | New Haven | Connecticut | 06510 | United States |
| Mayo Clinic-Jacksonville | Jacksonville | Florida | 32224 | United States |
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Sarah Cannon Research Inst. | Nashville | Tennessee | 37203 | United States |
| Vanderbilt Medical Center | Nashville | Tennessee | 37232-7610 | United States |
| The Netherlands Cancer Institute of Amsterdam | Amsterdam | 1066 CX | Netherlands |
| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| D000077190 | Interferon alpha-2 |
| D000074324 | Ipilimumab |
| C543332 | obinutuzumab |
| C100416 | peginterferon alfa-2a |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D016898 | Interferon-alpha |
| D007370 | Interferon Type I |
| D007372 | Interferons |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
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