A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2)

NCT02108652 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: GO29293 (Cohort 2)IMvigor 2102013-005486-39
• Study Type: interventional
• Target: 310
• Locations: 8 countries
• Sites: 77

Brief Summary

This Phase II, single-arm study is designed to evaluate the effect of atezolizumab treatment in participants with locally advanced or metastatic urothelial bladder cancer. Participants will be enrolled into 1 of 2 cohorts. Cohort 1 will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. The results of Cohort 1 are reported separately (NCT02951767). Cohort 2 (reported here) will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. Participants in both cohorts will be given a 1200 milligrams (mg) intravenous (IV) dose of atezolizumab on Day 1 of 21-day cycles. Treatment of participants in Cohort 1 will continue until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or unmanageable toxicity. Treatment of participants in Cohort 2 will continue until loss of clinical benefit or unmanageable toxicity.

Conditions

Bladder Cancer

Keywords

anti-PD-L1; PD-L1; MPDL3280A; PD-1; bladder cancer; atezolizumab; Tecentriq

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With a Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Independent Review Facility (IRF) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.

  Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

• Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According Modified RECIST

  Tumor response was assessed by the investigator according to modified RECIST. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.

  Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Secondary Outcomes (16)

• Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1

  Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

• DOR as Assessed by the Investigator According to RECIST v1.1

  Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

• DOR as Assessed by the Investigator According to Modified RECIST

  Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

• Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1

  Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

• Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1

  Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Study Arms (1)

Cohort 2: Participants With Second-line or Beyond Treatments

EXPERIMENTAL

Participants with advanced disease who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting will receive atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg given by IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria/loss of clinical benefit or unmanageable toxicity.

Also known as: MPDL3280A, Tecentriq

Cohort 2: Participants With Second-line or Beyond Treatments

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
• Representative tumor specimens as specified by the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than or equal to (\>=) 12 weeks
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end organ function
• Disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin \[GC\], methotrexate, vinblastine, doxorubicin, and cisplatin \[MVAC\], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence.
• A regimen was defined as participants receiving at least two cycles of a platinum-containing regimen. Participants who had received one cycle of a platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or Grade 3 or 4 non-hematologic toxicity could also be eligible.
• Participants who received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen were considered as second-line participants.

You may not qualify if:

• Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled hypercalcemia (greater than \[\>\] 1.5 millimoles per liter \[mmol/L\] ionized calcium or Ca \> 12 milligrams per deciliter \[mg/dL\] or corrected serum calcium \> upper limits of normal \[ULN\]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Malignancies other than urothelial bladder cancer 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 or incidental prostate cancer
• Pregnant and lactating women
• 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
• Serum albumin less than (\<) 2.5 grams per deciliter (g/dL)
• Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis
• Severe infections within 4 weeks prior to Cycle 1, Day 1
• Significant cardiovascular disease

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (77)

University of Alabama At Birmingham

Birmingham, Alabama, 35294, United States

Location

Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

Arizona Oncology - HOPE Wilmot

Tucson, Arizona, 85710, United States

Location

UCLA

Los Angeles, California, 90024, United States

Location

The Angeles Clinic and Research Institute - W LA Office

Los Angeles, California, 90025, United States

Location

USC Norris Cancer Center

Los Angeles, California, 90033, United States

Location

UCSF

San Francisco, California, 94143-0106, United States

Location

Kaiser Permanente - San Marcos

San Marcos, California, 92069, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5820, United States

Location

Kaiser Permanente; Oncology Clinical Trials

Vallejo, California, 94589, United States

Location

Rocky Mountain Cancer Center - Aurora

Aurora, Colorado, 80012, United States

Location

University Of Colorado

Aurora, Colorado, 80045, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Yale Cancer Center ; Medical Oncology

New Haven, Connecticut, 06520, United States

Location

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, 20057, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Piedmont Cancer Institute, PC

Atlanta, Georgia, 30318, United States

Location

University of Chicago; Hematology/Oncology

Chicago, Illinois, 60637, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Indiana University Health; Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40402, United States

Location

Massachusetts General Hospital;Oncology

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Inst. ; Dept. of Medical Oncology

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Medicine

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Minnesota Oncology Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Urology Cancer Center & GU Research Network

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89128, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12208, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Mount Sinai School of Medicine - Tisch Cancer Institute

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

Case Western Reserve Univ; Hem/Onc

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Willamette Valley Cancer Ctr - 520 Country Club

Eugene, Oregon, 97401-8122, United States

Location

Kimmel Cancer Center Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Cancer Center - Tennessee Oncology, Pllc

Nashville, Tennessee, 37203, United States

Location

Ctr for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - Houston (Gessner)

Houston, Texas, 77024, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates - Lake Wright Cancer Center

Norfolk, Virginia, 23502, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Bcca - Cancer Center Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, L1G 2B9, Canada

Location

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, H3T 1E2, Canada

Location

APHP - Hospital Saint Louis

Paris, 75475, France

Location

Hopital Foch; Oncologie

Suresnes, 92151, France

Location

Institut Gustave Roussy; Oncologie Medicale

Villejuif, 94800, France

Location

Charité - Universitätsmedizin Berlin; CC 8: Chirurgische Medizin; Klinik für Urologie

Berlin, 12200, Germany

Location

Universitätsklinikum Düsseldorf; Urologische Klinik

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II

Hamburg, 20246, Germany

Location

Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik

München, 81675, Germany

Location

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, 20133, Italy

Location

Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia

Arezzo, Tuscany, 52100, Italy

Location

The Netherlands Cancer Institute - Antoni Van Leeuwenhoekziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, 41013, Spain

Location

University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Barts and The London

London, EC1M 6BQ, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, L63 4JY, United Kingdom

Location

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (8)

• Holm JS, Funt SA, Borch A, Munk KK, Bjerregaard AM, Reading JL, Maher C, Regazzi A, Wong P, Al-Ahmadie H, Iyer G, Tamhane T, Bentzen AK, Herschend NO, De Wolf S, Snyder A, Merghoub T, Wolchok JD, Nielsen M, Rosenberg JE, Bajorin DF, Hadrup SR. Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma. Nat Commun. 2022 Apr 11;13(1):1935. doi: 10.1038/s41467-022-29342-0.

  PMID: 35410325 DERIVED

• Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.

  PMID: 33241650 DERIVED

• Teo MY, Seier K, Ostrovnaya I, Regazzi AM, Kania BE, Moran MM, Cipolla CK, Bluth MJ, Chaim J, Al-Ahmadie H, Snyder A, Carlo MI, Solit DB, Berger MF, Funt S, Wolchok JD, Iyer G, Bajorin DF, Callahan MK, Rosenberg JE. Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers. J Clin Oncol. 2018 Jun 10;36(17):1685-1694. doi: 10.1200/JCO.2017.75.7740. Epub 2018 Feb 28.

  PMID: 29489427 DERIVED

• Perez-Gracia JL, Loriot Y, Rosenberg JE, Powles T, Necchi A, Hussain SA, Morales-Barrera R, Retz MM, Niegisch G, Duran I, Theodore C, Grande E, Shen X, Wang J, Nelson B, Derleth CL, van der Heijden MS. Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens. Eur Urol. 2018 Mar;73(3):462-468. doi: 10.1016/j.eururo.2017.11.023. Epub 2017 Dec 20.

  PMID: 29273410 DERIVED

• Necchi A, Joseph RW, Loriot Y, Hoffman-Censits J, Perez-Gracia JL, Petrylak DP, Derleth CL, Tayama D, Zhu Q, Ding B, Kaiser C, Rosenberg JE. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study. Ann Oncol. 2017 Dec 1;28(12):3044-3050. doi: 10.1093/annonc/mdx518.

  PMID: 28950298 DERIVED

• Snyder A, Nathanson T, Funt SA, Ahuja A, Buros Novik J, Hellmann MD, Chang E, Aksoy BA, Al-Ahmadie H, Yusko E, Vignali M, Benzeno S, Boyd M, Moran M, Iyer G, Robins HS, Mardis ER, Merghoub T, Hammerbacher J, Rosenberg JE, Bajorin DF. Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: An exploratory multi-omic analysis. PLoS Med. 2017 May 26;14(5):e1002309. doi: 10.1371/journal.pmed.1002309. eCollection 2017 May.

  PMID: 28552987 DERIVED

• Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Duran I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thastrom A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2. Epub 2016 Dec 8.

  PMID: 27939400 DERIVED

• Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4.

  PMID: 26952546 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 7, 2014
• First Posted: April 9, 2014
• Study Start: May 31, 2014
• Primary Completion: July 4, 2016
• Study Completion: February 28, 2023
• Last Updated: March 28, 2024
• Results First Posted: January 4, 2017

Record last verified: 2024-03

Locations

GB (5); DE (5); ES (7); FR (3); US (47); NL (1); IT (2); CA (7)