A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer

NCT04677504 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GO42661
• Study Type: interventional
• Target: 162
• Locations: 13 countries
• Sites: 49

Brief Summary

This study will evaluate the efficacy and safety of atezolizumab with bevacizumab in combination with cisplatin and gemcitabine(CisGem), compared with atezolizumab in combination with CisGem, in participants with advanced biliary tract cancer (BTC) who have not received prior systemic therapy. Treatment will consist of a chemotherapy combination phase followed by a cancer immunotherapy (CIT)/placebo phase.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)

  Randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)

Secondary Outcomes (9)

• Overall Survival (OS)

  Randomization to death from any cause (up to approximately 23 months)

• Confirmed Objective Response Rate (ORR)

  Randomization up to approximately 14 months

• Duration of Response (DOR)

  First occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)

• Disease Control Rate (DCR)

  Randomization up to approximately 14 months

• Time to Confirmed Deterioration (TTCD)

  Randomization to the first clinically meaningful deterioration (up to approximately 14 months)

Study Arms (2)

Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev

EXPERIMENTAL

Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cisplatin; Drug: Gemcitabine

Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO

ACTIVE COMPARATOR

Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive placebo matching bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.

Drug: Atezolizumab; Other: Placebo; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Atezolizumab DRUG

Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Also known as: Tecentriq

Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev; Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO

Bevacizumab DRUG

Bevacizumab will be administered at a dose of 15 mg/kg intravenously on Day 1 of each 21-day cycle after atezolizumab.

Also known as: Avastin

Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev

Placebo OTHER

Placebo matching bevacizumab will be administered intravenously on Day 1 of each 21-day cycle after atezolizumab.

Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO

Cisplatin DRUG

Cisplatin will be administered intravenously at a dose of 25 mg/m\^2 on Days 1 and 8 of each 21-day cycle for Cycles 1-8.

Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev; Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO

Gemcitabine DRUG

Gemcitabine will be administered intravenously at a dose of 1000 mg/m\^2 on Days 1 and 8 of each 21-day cycle for Cycles 1-8.

Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev; Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO

Eligibility Criteria

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

You may qualify if:

• Considered to be eligible to receive platinum-based chemotherapy, in the investigator's judgment
• Documentation of recurrent/metastatic or locally advanced unresectable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) scans
• Histologically or cytologically confirmed diagnosis of iCCA, eCCA, or GBC
• No prior systemic therapy for advanced BTC
• At least one measurable untreated lesion (per RECIST v1.1)
• Adequate biliary drainage with no evidence of ongoing infection
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Life expectancy of \> 3 months
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

You may not qualify if:

• Recurrent disease \<=6 months after curative surgery or \<= 6 months after the completion of adjuvant therapy
• Prior local regional therapy such as radioembolization
• Combined or mixed hepatocellular/cholangiocarcinoma
• Clinically significant hepatic encephalopathy within the 12 months prior to Day 1 of Cycle 1
• National Cancer Institute Common Terminoogy Criteria for Adverse Events Grade \>= 2 peripheral neuropathy
• Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to Day 1 of Cycle 1
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab, cisplatin or gemcitabine
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
• History of malignancy other than BTC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Symptomatic, untreated, or actively progressing CNS metastases
• For patients with lung metastases, if one of the following criteria applies: Large, centrally located pulmonary metastases; Clear tumor infiltration into the thoracic great vessels seen on imaging; Clear cavitation of pulmonary lesions seen on imaging
• Active tuberculosis
• Co-infection with HBV and HCV
• Treatment with systemic immunostimulatory agents or immunosuppressive medication

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (49)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

Sir Run Run Shaw Hospital Zhejiang University

Hangzhou, 310016, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Queen Mary Hospital; Dept. Of Haematology & Oncology

Hong Kong, Hong Kong

Location

Prince of Wales Hosp; Dept. Of Clinical Onc

Shatin, Hong Kong

Location

Fondazione Pascale; U.O. Sperimentazioni Cliniche

Napoli, Campania, 80100, Italy

Location

Azienda Ospedaliero Universitaria di Bologna; Istituto di Ematologia "Lorenzo e Ariosto Seragnoli"

Bologna, Emilia-Romagna, 40139, Italy

Location

Istituto Clinico Humanitas - Humanitas Cancer Center

Rozzano, Sicily, 20089, Italy

Location

IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II

Padua, Veneto, 35128, Italy

Location

SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej

Bytom, 41-902, Poland

Location

Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii

Gdansk, 80-214, Poland

Location

Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii

Koszalin, 75-581, Poland

Location

NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii

Warsaw, 02-034, Poland

Location

Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii

Wroc?aw, 53-413, Poland

Location

FSBI "National Medical Research Center of Oncology N.N. Blokhin?

Moscow, Moscow Oblast, 115478, Russia

Location

First Moscow State Medical University n.a. I.M. Sechenov

Moscow, Moscow Oblast, 119991, Russia

Location

SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"

Moskva, Moscow Oblast, 111123, Russia

Location

GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

CHA Bundang Medical Center

Gyeonggi-do, 13496, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Complejo Hospitalario de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron; Oncology

Barcelona, 08035, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Complejo Hospitalario de Orense; Servicio de Oncologia

Ourense, 32005, Spain

Location

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, 50009, Spain

Location

National Taiwan Uni Hospital; Dept of Oncology

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital; Department of Oncology

Taipei, 112201, Taiwan

Location

Maharaj Nakorn Chiang Mai Hosp; Oncology Unit

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital; Medical Oncology Unit

Khon Kaen, 40002, Thailand

Location

Sunpasitthiprasong Hospital; Oncology and/or Hematology

Ubon Ratchathani, 34000, Thailand

Location

Adana Ac?badem Hospital Oncology Department

Adana, 01130, Turkey (Türkiye)

Location

Memorial Ankara Hastanesi

Ankara, 06520, Turkey (Türkiye)

Location

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, 44280, Turkey (Türkiye)

Location

Koc Universitesi Hastanesi; T?bbi Onkoloji

Zeyt?nburnu, 34010, Turkey (Türkiye)

Location

SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU

Kharkiv, Kharkiv Governorate, 61018, Ukraine

Location

?Kharkov Regional Oncology Center

Kharkiv, Kharkiv Governorate, 61070, Ukraine

Location

SI "Shalimov National Institute of Surgery and Transplantation" of Nat.Acad of Med.Sci of Ukraine

Kyiv, KIEV Governorate, 03126, Ukraine

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Royal Free Hospital

London, NW3 2QS, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Royal Marsden Hospital (Sutton)

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Macarulla T, Ren Z, Chon HJ, Park JO, Kim JW, Pressiani T, Li D, Zhukova L, Zhu AX, Chen MH, Hack SP, Wu S, Liu B, Guan X, Lu S, Wang Y, El-Khoueiry AB. Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial. J Clin Oncol. 2025 Feb 10;43(5):545-557. doi: 10.1200/JCO.24.00337. Epub 2024 Oct 18.

  PMID: 39423355 DERIVED

• Hack SP, Verret W, Mulla S, Liu B, Wang Y, Macarulla T, Ren Z, El-Khoueiry AB, Zhu AX. IMbrave 151: a randomized phase II trial of atezolizumab combined with bevacizumab and chemotherapy in patients with advanced biliary tract cancer. Ther Adv Med Oncol. 2021 Jul 31;13:17588359211036544. doi: 10.1177/17588359211036544. eCollection 2021.

  PMID: 34377158 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

atezolizumab; Bevacizumab; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: December 21, 2020
• Study Start: February 23, 2021
• Primary Completion: May 16, 2022
• Study Completion: August 25, 2023
• Last Updated: July 3, 2024
• Results First Posted: June 29, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

US (5); CN (3); TW (2); TH (3); RU (4); GB (4); KR (5); ES (5); IT (4); UA (3); HK (2); PL (5); TU (4)