Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT02807636
• Date of registration: 17/06/2016
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma IMvigor130
• Scientific title: A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination With Platinum-Based Chemotherapy in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma
• Date of first enrolment: June 30, 2016
• Target sample size: 1213
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02807636
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Czech Republic, Czechia, Estonia, Finland, Georgia, Greece, Hong Kong, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovenia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria

- Considered to be eligible to receive platinum-based chemotherapy, in the
investigator's judgment

- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
(
- Histologically documented, locally advanced (T4b, any N; or any T, N2-3) or metastatic
urothelial carcinoma (mUC) (M1, Stage IV) (also termed transitional cell carcinoma
[TCC] or urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis,
ureters, urinary bladder, and urethra)

- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
blocks (blocks preferred) or at least 15 unstained slides, with an associated
pathology report, for central testing and determined to be evaluable for tumor PD-L1
expression prior to study enrollment; participants who have fewer than 15 unstained
slides available at baseline (but no less than [<] 10) may be eligible following
discussion with the Medical Monitor

- No prior chemotherapy for inoperable locally advanced or mUC

- For participants who received prior adjuvant/neoadjuvant chemotherapy or
chemo-radiation for urothelial carcinoma, a treatment-free interval more than (>) 12
months between the last treatment administration and the date of recurrence is
required in order to be considered treatment naive in the metastatic setting

- Prior local intravesical chemotherapy or immunotherapy is allowed if completed at
least 4 weeks prior to the initiation of study treatment

- Measurable disease, as defined by RECIST v1.1

- Adequate hematologic and end-organ function

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of <1% per year during the treatment period and for at least 6 months after the last
dose of carboplatin, cisplatin, or gemcitabine or for 5 months after the last dose of
atezolizumab

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm

Exclusion Criteria:

- Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3
weeks prior to initiation of study treatment

- Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 28 days prior to enrolment

- Active or untreated CNS metastases as determined by computed tomography (CT) or
magnetic resonance imaging evaluation during screening and prior radiographic
assessments

- Participants with treated asymptomatic central nervous system (CNS) metastases are
eligible, provided they meet all of the following criteria: * Evaluable or measurable
disease outside the CNS * No metastases to midbrain, pons, medulla, or within 10 mm of
the optic apparatus (optic nerves and chiasm) * No history of intracranial or spinal
cord hemorrhage * No ongoing requirement for corticosteroid as therapy for CNS
disease; anti-convulsants at a stable dose are allowed * No evidence of significant
vasogenic edema * No stereotactic radiation, whole-brain radiation or neurosurgical
resection within 4 weeks prior to Cycle 1, Day 1 * Radiographic demonstration of
interim stability (i.e., no progression) between the completion of CNS-directed
therapy and the screening radiographic study * Screening CNS radiographic study >/=4
weeks since completion of radiotherapy or surgical resection and >/=2 weeks since
discontinuation of corticosteroids

- Prior treatment with CD137 agonists, anti-CTLA-4, anti-programmed death-1 (PD-1), or
anti-PD-L1 therapeutic antibody or pathway-targeting agents

- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents)
within 2 weeks prior to Cycle 1, Day 1 or anticipated requirement for systemic
immunosuppressive medications during the study

- Leptomeningeal disease

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)

- Uncontrolled tumour-related pain or hypercalcemia

- Significant cardiovascular disease including known left ventricular ejection fraction
(LVEF) <40%

- Severe infections within 4 weeks before randomization or therapeutic oral or IV
antibiotics within 2 weeks before randomization

- Major surgical procedure within 4 weeks prior to randomization or anticipation of need
for a major surgical procedure during the course of the study other than for diagnosis

- Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1

- Life expectancy of <12 weeks

- Pregnant or lactating, or intending to become pregnant during the study

- Serum albumin <25 gram per liter (g/L)

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or any component of the atezolizumab formulation

- History of autoimmune disease

- Participants with prior allogeneic stem cell or solid organ transplantation

- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan

- Positive test for human immunodeficiency virus (HIV)

- Active hepatitis B or hepatitis C

- Active tuberculosis

- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Urothelial Carcinoma

Intervention(s)

Drug: Gemcitabine

Other: Placebo

Drug: Atezolizumab

Drug: Cisplatin

Drug: Carboplatin

Primary Outcome(s)

Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Baseline until death due to any cause (up to approximately 73 months)]

Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Baseline until death due to any cause (up to approximately 73 months)]

Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Baseline up to first documented disease progression or death, whichever occurs first (up to approximately 35 months)]

Secondary Outcome(s)

Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Up to approximately 73 months]

Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)]

PFS Event Free Rate [Time Frame: Year 1]

Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm [Time Frame: Up to approximately 73 months]

Maximum Atezolizumab Serum Concentration [Time Frame: Cycle 1 Day 1]

Minimum Atezolizumab Serum Concentration [Time Frame: Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, Cycle 16 Day 1, Cycle 24 Day 1, Cycle 32 Day 1, Day 120 post dose of last blinded atezolizumab treatment, and study drug early discontinuation]

Percentage of Participants With Adverse Events (AEs) Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [Time Frame: Baseline up to 90 months]

Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)]

Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs) [Time Frame: Up to approximately 35 months]

Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)]

Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)]

Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Up to approximately 73 months]

Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm [Time Frame: Up to approximately 73 months]

Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 35 months)]

OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Year 1]

OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm [Time Frame: Year 1]

IRF-PFS [Time Frame: Randomization to first documented disease progression or death from any cause (up to 35 months)]

Secondary ID(s)

2016-000250-35

WO30070

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 13/12/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02807636