Phase 3
N=915
A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)
Renal Cell Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT02420821 ↗Enrolled (actual)
915
Serious AEs
40.1%
Results posted
Oct 2018
Primary outcome: Primary: Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population — 69.6; 58.4 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug); Bevacizumab (Drug); Sunitinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Feb 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population |
69.6; 58.4 | — |
| PRIMARY Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population |
7.5; 11.2 | 0.0205 sig |
| PRIMARY Percentage of Participants Who Died of Any Cause in ITT Population |
55.3; 54.8 | — |
| PRIMARY Overall Survival (OS) in ITT Population |
35.3; 36.1 | 0.2675 |
| SECONDARY Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population |
56.5; 53.9 | — |
| SECONDARY OS in PD-L1-Selected Population |
31.6; 38.7 | 0.263 |
| SECONDARY Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population |
63.6; 60.4 | — |
| SECONDARY PFS as Determined by an IRC According to RECIST v1.1 in ITT Population |
8.3; 9.6 | 0.1218 |
| SECONDARY Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population |
64.7; 62.9 | — |
| SECONDARY PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population |
7.2; 8.9 | 0.6138 |
| SECONDARY Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable Population |
33.3; 36.6 | 0.2733 |
| SECONDARY Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population |
14.2; 16.6 | — |
| SECONDARY Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population |
31.3; 33.3 | 0.5121 |
| SECONDARY DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population |
18.6; NA | — |
| SECONDARY Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population |
58.1; 55.1 | — |
| SECONDARY PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population |
12.3; 13.9 | 0.0606 |
| SECONDARY Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population |
35.0; 40.1 | 0.1011 |
| SECONDARY DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population |
19.4; 19.4 | — |
| SECONDARY Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population |
63.8; 60.1 | — |
| SECONDARY PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population |
8.4; 11.2 | 0.0254 sig |
| SECONDARY Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology |
85.1; 67.6 | — |
| SECONDARY PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology |
5.3; 8.3 | 0.0020 sig |
| SECONDARY Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology |
77.0; 64.7 | — |
| SECONDARY OS in Participants With Sarcomatoid Histology |
15.4; 21.7 | 0.0497 sig |
| SECONDARY Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score |
1.28; 0.54; 0.76; 0.56; 1.58; 0.56 | <0.0001 sig |
| SECONDARY Change From Baseline in Symptom Severity as Determined by MDASI Part I Score |
1.41; 0.92; 1.83; 1.20; 1.20; 0.29 | 0.0010 sig |
| SECONDARY Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score |
2.11; 2.08; 0.30; 0.37; 1.26; 1.06 | — |
| SECONDARY Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item |
3.08; 2.98; 0.34; 0.50; 1.32; 1.26 | — |
| SECONDARY Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score |
-1.08; -0.36; -0.87; -0.45; -1.13; -0.43 | <0.0001 sig |
| SECONDARY Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab |
16; 95; 1 | — |
| SECONDARY Number of Participants With ATAs Against Bevacizumab |
24; 4; 0 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) for Atezolizumab |
376 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) for Atezolizumab |
85.6; 127 | — |
| SECONDARY Cmax for Bevacizumab |
339 | — |
| SECONDARY Cmin for Bevacizumab |
135 | — |
Summary
This multi-center, randomized, open-label study will evaluate the efficacy and safety of atezolizumab plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic RCC who have not received prior systemic active or experimental therapy, either in the adjuvant or metastatic setting.
Eligibility Criteria
Inclusion Criteria
- Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
- Evaluable Memorial Sloan Kettering Cancer Center risk score
- Measurable disease, as defined by RECIST v1.1
- Karnofsky performance status greater than or equal to 70%
- Adequate hematologic and end-organ function prior to randomization
Exclusion Criteria
Disease-Specific Exclusions:
- Radiotherapy for RCC within 14 days prior to treatment
- Active central nervous system disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites
- Uncontrolled hypercalcemia
- Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death
General Medical Exclusions:
- Life expectancy less than 12 weeks
- Participation in another experimental drug study within 4 weeks prior to treatment
- Pregnant or lactating women
- Known hypersensitivity to any component of atezolizumab or other study medication
- History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
- Positive human immunodeficiency virus test
- Active or chronic hepatitis B or C
- Severe infections within 4 weeks prior to treatment
- Exposure to oral or IV antibiotics within 2 weeks prior to treatment
- Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
- Significant cardiovascular disease
- Prior allogeneic stem cell or solid organ transplantation
Exclusion Criteria Related to Medications:
- Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment
Bevacizumab- and Sunitinib-Specific Exclusions:
- History of hypertensive crisis or hypertensive encephalopathy
- Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds
Data sourced from ClinicalTrials.gov (NCT02420821). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.