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)
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 |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
Drug: BTCT4465A (Mosunetuzumab) SC
Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.
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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:
Drug: BTCT4465A (Mosunetuzumab) SC
Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.
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Outcome Measures
Primary Outcome Measures
- 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)]
- 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)]
- BTCT4465A (Mosunetuzumab) Serum Concentration [Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)]
- Atezolizumab Serum Concentration [Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)]
- 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
- 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)]
- 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)]
- Overall Survival [Baseline until death from any cause (up to approximately 4 years)]
- 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
- 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
Key Inclusion Criteria:
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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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
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Adequate hepatic, hematologic, and renal function
Key Exclusion Criteria:
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Pregnant or lactating women
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Monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, chemotherapy, or other investigational anti-cancer agent within 4 weeks prior to study drug
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Treatment with radiotherapy within 2 weeks prior to the first BTCT4465A (Mosunetuzumab) administration
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Systemic immunosuppressive medication within 2 weeks prior to study drug
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Autologous stem cell transplantation (SCT) within 100 days prior to study drug, or any prior allogeneic SCT or solid organ transplantation
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Autoimmune disease with the exception of controlled/treated hypothyroidism, disease-related immune thrombocytopenic purpura, or hemolytic anemia
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History of central nervous system (CNS) lymphoma or other CNS disease
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Significant cardiovascular or pulmonary disease
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Hepatitis B or C or human immunodeficiency virus (HIV)
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Receipt of a live attenuated vaccine within 4 weeks prior to study drug
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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 | |
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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.- GO29781