A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

Sponsor
Genentech, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT02500407
Collaborator
(none)
836
56
2
98
14.9
0.2

Study Details

Study Description

Brief Summary

This is a Phase 1/2 dose-escalation study of BTCT4465A (Mosunetuzumab) administered as a single agent and in combination with atezolizumab in participants with relapsed or refractory B-cell NHL and CLL. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Condition or Disease Intervention/Treatment Phase
  • Drug: BTCT4465A (Mosunetuzumab) IV
  • Drug: Atezolizumab
  • Drug: BTCT4465A (Mosunetuzumab) SC
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
836 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Multicenter, Phase I/II Trial Evaluating the Safety, Efficacy, and Pharmacokinetics of Escalating Doses of Mosunetuzumab (BTCT4465A) as a Single Agent and Combined With Atezolizumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia
Actual Study Start Date :
Sep 15, 2015
Anticipated Primary Completion Date :
Nov 15, 2023
Anticipated Study Completion Date :
Nov 15, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation

Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level.

Drug: BTCT4465A (Mosunetuzumab) IV
Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via IV infusion.

Drug: Atezolizumab
Participants assigned to an atezolizumab combination group will receive atezolizumab 1200 mg administered as an IV infusion in combination with BTCT4465A (Mosunetuzumab).
Other Names:
  • Tecentriq
  • Drug: BTCT4465A (Mosunetuzumab) SC
    Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.

    Experimental: Dose Expansion

    Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.

    Drug: BTCT4465A (Mosunetuzumab) IV
    Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via IV infusion.

    Drug: Atezolizumab
    Participants assigned to an atezolizumab combination group will receive atezolizumab 1200 mg administered as an IV infusion in combination with BTCT4465A (Mosunetuzumab).
    Other Names:
  • Tecentriq
  • Drug: BTCT4465A (Mosunetuzumab) SC
    Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of BTCT4465A (Mosunetuzumab) [BTCT4465A (Mosunetuzumab) single agent: Cycle 1; BTCT4465A (Mosunetuzumab) in combination with atezolizumab: during the first cycle that BTCT4465A (Mosunetuzumab) and atezolizumab are administered concurrently (cycle length = 21 days)]

    2. Percentage of Participants With Adverse Events [Cycle 1 Day 1 until 90 days after the last infusion (cycle length = 21 days; up to approximately 14 months)]

    3. BTCT4465A (Mosunetuzumab) Serum Concentration [Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)]

    4. Atezolizumab Serum Concentration [Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)]

    5. Percentage of Participants with Complete Response as Assessed Using Standard Criteria for NHL [Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal)]

    Secondary Outcome Measures

    1. Duration of Response as Assessed Using Standard Criteria for NHL [Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal)]

    2. Progression-Free Survival (PFS) as Assessed Using Standard Criteria for NHL [Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, withdrawal, or death from any cause)]

    3. Overall Survival [Baseline until death from any cause (up to approximately 4 years)]

    4. European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Scores to Assess Health-Related Quality of Life (HRQoL) [Baseline until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 4 years).]

      The Functional Assessment of Cancer Therapy-Lymphoma (FACT-lym) Subscale, and the EuroQol 5 Dimension-5 Level (EQ-5D-5L) Questionnaire scores will also be used to assess HRQoL

    5. Objective Response Rate (ORR) [Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    • B-cell hematologic malignancies expected to express the cluster of differentiation 20 (CD20) antigen who have relapsed after or failed to respond to at least one prior treatment regimen and for whom there is no available therapy expected to improve survival

    • Adequate hepatic, hematologic, and renal function

    Key Exclusion Criteria:
    • Pregnant or lactating women

    • Monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, chemotherapy, or other investigational anti-cancer agent within 4 weeks prior to study drug

    • Treatment with radiotherapy within 2 weeks prior to the first BTCT4465A (Mosunetuzumab) administration

    • Systemic immunosuppressive medication within 2 weeks prior to study drug

    • Autologous stem cell transplantation (SCT) within 100 days prior to study drug, or any prior allogeneic SCT or solid organ transplantation

    • Autoimmune disease with the exception of controlled/treated hypothyroidism, disease-related immune thrombocytopenic purpura, or hemolytic anemia

    • History of central nervous system (CNS) lymphoma or other CNS disease

    • Significant cardiovascular or pulmonary disease

    • Hepatitis B or C or human immunodeficiency virus (HIV)

    • Receipt of a live attenuated vaccine within 4 weeks prior to study drug

    • Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first BTCT4465A (Mosunetuzumab) administration

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope National Medical Center Duarte California United States 91010
    2 University of California San Diego Moores Cancer Center La Jolla California United States 92037
    3 Sansum Medical Clinic, Inc. Santa Barbara California United States 93105
    4 Rocky Mountain Cancer Center Denver Colorado United States 80218
    5 Yale University School Of Medicine New Haven Connecticut United States 06519
    6 Washington University; Wash Uni. Sch. Of Med Saint Louis Missouri United States 63110
    7 Hackensack University Medical Center Hackensack New Jersey United States 07601
    8 Memorial Sloan Kettering Bergen Montvale New Jersey United States 07645
    9 Memorial Sloan Kettering Cancer Center - Commack Commack New York United States 11725
    10 Memorial Sloan-Kettering Cancer Center Commack New York United States 11725
    11 Memorial Sloan Kettering Cancer Center at Westchester Harrison New York United States 10604
    12 New York Uni Medical Center New York New York United States 10016
    13 Willamette Valley Cancer Insitute and Research Center Springfield Oregon United States 97477
    14 University of Pennsylvania; School of Medicine Philadelphia Pennsylvania United States 19104
    15 Tennessee Oncology Nashville Tennessee United States 37203
    16 MD Anderson Cancer Center Houston Texas United States 77030
    17 Fred Hutchinson Cancer Research Center Seattle Washington United States
    18 St Vincent's Hospital Sydney Darlinghurst New South Wales Australia 2010
    19 Wollongong Hospital; Cancer Care Centre Wollongong New South Wales Australia 2500
    20 Icon Cancer Care South Brisbane South Brisbane Queensland Australia 4101
    21 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
    22 Royal Adelaide Hospital; Haematology Clinical Trials Adelaide South Australia Australia 5000
    23 St. Vincent's Hospital Melbourne Fitzroy South Australia Australia 3065
    24 Royal Hobart Hospital Hobart Tasmania Australia 7000
    25 Monash Health Clinical Trial Pharmacy department Clayton Victoria Australia 3168
    26 Peter MacCallum Cancer Centre-East Melbourne Melbourne Victoria Australia 3000
    27 The Alfred Melbourne Victoria Australia 3124
    28 Linear Clinical Research Limited Nedlands Western Australia Australia 6009
    29 The Perth Blood Institute Nedlands Western Australia Australia 6009
    30 BC Cancer Agency Vancouver Centre - PARENT Vancouver British Columbia Canada V5Z 1H3
    31 Princess Margaret Hospital; Department of Med Oncology Toronto Ontario Canada M5G 2M9
    32 Jewish General Hospital; Research Unit Montréal Quebec Canada H3T 1E2
    33 Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez Lille France 59037
    34 CHRU Montpellier; SMPEA Peyre Plantade Centre de Ressources Autisme Montpellier France 34295
    35 CHU NANTES - Hôtel Dieu; Service d'Hematologie Clinique Nantes France 44093
    36 Hôpital St Louis - Service de Dermatologie II Paris France 75010
    37 Centre Hospitalier Lyon Sud Pierre-Benite France 69495
    38 Institut Universitaire du Cancer de Toulouse-Oncopole Toulouse France 31059
    39 DIAKO Ev. Diakonie-Krankenhaus Bremen GmbH; Med. Klinik II; Hämatologie und internistische Onkologie Bremen Germany 28239
    40 St. Johannes Hospital; Abt. für Hämatologie und Onkologie Dortmund Germany 44137
    41 Universitätsklinikum Heidelberg Heidelberg Germany 69120
    42 Universitatsklinikum Koln; Apotheke Uniklinik Koln Koln Germany 50931
    43 Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz Mainz Germany 55101
    44 Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III München Germany 81377
    45 Universitatsklinikum Munster Münster Germany 48149
    46 Universitätsklinikum Würzburg Würzburg Germany 97080
    47 Seoul National University Hospital Seoul Korea, Republic of 03080
    48 Asan Medical Center Seoul Korea, Republic of 05505
    49 Samsung Medical Center Seoul Korea, Republic of 06351
    50 Clínica Universidad de Navarra Pamplona Navarra Spain 31620
    51 Hospital Universitario Vall d'Hebron Barcelona Spain 08035
    52 Hospital Universitario La Paz Madrid Spain 280146
    53 Complejo Asistencial Universitario de Salamanca Salamanca Spain 37007
    54 Barts Cancer Institute London United Kingdom E1 2AT
    55 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
    56 Royal Marsden Hospital; Institute of Cancer Research; Pharmacy Stores Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT02500407
    Other Study ID Numbers:
    • GO29781
    First Posted:
    Jul 16, 2015
    Last Update Posted:
    Aug 5, 2022
    Last Verified:
    Aug 1, 2022

    Study Results

    No Results Posted as of Aug 5, 2022