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Phase 2 N=305 Randomized Treatment

A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma

Renal Cell Carcinoma

Enrolled (actual)
305
Serious AEs
36.6%
Results posted
Dec 2017
Primary outcome: Primary: Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population — 66.3; 59.2; 58.4 percentage of participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
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
Oct 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population
66.3; 59.2; 58.4
PRIMARY
Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population
11.7; 6.1; 8.4 0.9819
PRIMARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population
58.0; 59.3; 68.3
PRIMARY
PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
14.7; 5.5; 7.8 0.0952
SECONDARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
55.6; 61.4; 73.8
SECONDARY
PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
17.5; 5.7; 7.1 0.0153 sig
SECONDARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
57.8; 77.3; 83.3
SECONDARY
PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
16.6; 5.5; 6.8 0.0086 sig
SECONDARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
59.0; 58.2; 65.0
SECONDARY
PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
13.8; 5.7; 8.2 0.1973
SECONDARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
63.9; 76.4; 78.3
SECONDARY
PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
11.1; 5.5; 7.1 0.0830
SECONDARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population
71.3; 75.7; 75.2
SECONDARY
PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population
11.1; 5.5; 7.8 0.2541
SECONDARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population
66.0; 74.1; 81.7
SECONDARY
PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
11.1; 5.5; 7.0 0.0351 sig
SECONDARY
Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population
31.7; 25.2; 28.7 0.6492
SECONDARY
Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
46.0; 27.8; 26.7 0.0141 sig
SECONDARY
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population
34.7; 23.3; 32.7 0.8068
SECONDARY
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
48.0; 25.9; 28.3 0.0199 sig
SECONDARY
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population
37.6; 25.2; 33.7 0.6231
SECONDARY
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
52.0; 27.8; 30.0 0.0111 sig
SECONDARY
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population
60.4; 61.2; 63.4
SECONDARY
PFS Per Modified RECIST Via Investigator Assessment in ITT Population
16.7; 10.9; 9.9 0.0863
SECONDARY
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population
52.0; 59.3; 75.0
SECONDARY
PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
21.7; 10.9; 8.4 0.0021 sig
SECONDARY
Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population
22.1; NA; NA
SECONDARY
DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population
NA; NA; 14.2
SECONDARY
DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
22.1; NA; NA
SECONDARY
DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
22.4; NA; 14.1
SECONDARY
DOR Per Modified RECIST Via Investigator Assessment in ITT Population
NA; NA; 16.6
SECONDARY
DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
22.4; NA; 16.6
SECONDARY
Percentage of Participants Who Died in ITT Population
38.6; 35.0; 30.7
SECONDARY
Overall Survival (OS) in ITT Population
NA; NA; NA 0.2867
SECONDARY
Percentage of Participants Who Died in IC1/2/3 Population
38.0; 39.8; 35.0
SECONDARY
OS in IC1/2/3 Population
27.3; 30.2; NA 0.7879
SECONDARY
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population
24.4; 27.8
SECONDARY
DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population
NA; NA
SECONDARY
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population
59.1; 68.4
SECONDARY
PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population
12.6; 8.3
SECONDARY
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
34.0; 25.0
SECONDARY
Maximum Serum Concentration (Cmax) of Atezolizumab
335; 358; 418; 314
SECONDARY
Minimum Serum Concentration (Cmin) of Atezolizumab
72.6; 79.9; 174; 73.2; 122; 125
SECONDARY
Cmax of Bevacizumab
89.8; 433; 455
SECONDARY
Cmin of Bevacizumab
75.2; 101; 95.9
SECONDARY
M.D. Anderson Symptom Inventory (MDASI) Interference Score
1.60; 1.38; 1.79; 2.08; 1.26; 3.16
SECONDARY
Brief Fatigue Inventory (BFI) Fatigue Level Score
2.80; 2.52; 2.66; 3.80; 2.55; 4.42

Summary

This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.

Eligibility Criteria

Inclusion Criteria

  • Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting
  • Measurable disease, as defined by RECIST v1.1
  • Karnofsky performance score greater than or equal to (>/=) 70
  • Adequate hematologic and end-organ function as defined by protocol
  • Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol

Exclusion Criteria

Disease-Specific Exclusions:

  • Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control
  • Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia
  • Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome

General Medical Exclusions:

  • Life expectancy of less than (<) 12 weeks
  • Pregnant and lactating women
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • History of autoimmune disease
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease
  • Prior allogeneic stem cell or solid organ transplant

Exclusion Criteria Related to Medications:

  • Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1

Bevacizumab- and Sunitinib-Specific Exclusions:

  • Inadequately controlled hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association Class II or greater congestive heart failure
  • History of myocardial infarction or unstable angina, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01984242). 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.

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