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)

• ClinicalTrials.gov Identifier: NCT02500407
• Recruitment Status: Active, not recruiting
• First Posted: July 16, 2015
• Last Update Posted: May 16, 2023
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: July 14, 2015
• First Posted Date: July 16, 2015
• Last Update Posted Date: May 16, 2023
• Actual Study Start Date: September 15, 2015
• Estimated Primary Completion Date: November 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2021)

• Maximum Tolerated Dose (MTD) of BTCT4465A (Mosunetuzumab) [ Time Frame: 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 [ Time Frame: Cycle 1 Day 1 until 90 days after the last infusion (cycle length = 21 days; up to approximately 14 months) ]
• BTCT4465A (Mosunetuzumab) Serum Concentration [ Time Frame: Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months) ]
• Atezolizumab Serum Concentration [ Time Frame: 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 [ Time Frame: 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) ]

Original Primary Outcome Measures (submitted: July 14, 2015)

• Incidence of dose-limiting toxicities (DLTs) [ Time Frame: During Cycle 1 (up to 21 days) ]
• Incidence of adverse events [ Time Frame: From Cycle 1 Day 1 until 90 days after the last infusion (up to approximately 9 months) ]
• Area under the concentration-time curve (AUC) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 on Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) ]
• Maximum serum concentration (Cmax) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 on Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) ]
• Minimum serum concentration (Cmin) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 on Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) ]
• Clearance (CL) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 on Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) ]
• Volume of distribution at steady state (Vss) of BTCT4465A [ Time Frame: Pre-dose and post-dose on Days 1, 8, and 15 on Cycle 1 and on Days 1 and 8 of Cycles 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) ]

Current Secondary Outcome Measures (submitted: May 21, 2018)

• Duration of Response as Assessed Using Standard Criteria for NHL [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) ]

Original Secondary Outcome Measures (submitted: July 14, 2015)

• Incidence of objective tumor response [ Time Frame: At Screening and every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 3 years) ]
• Duration of objective tumor response [ Time Frame: At Screening and every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 3 years) ]
• Progression-free survival (PFS) [ Time Frame: At Screening and every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 3 years) ]
• Incidence of anti-therapeutic antibodies (ATAs) to BTCT4465A [ Time Frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8 and within 30 days after the last infusion (up to approximately 7 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lymphocytic Leukemia, Chronic
• Lymphoma, Non Hodgkin

Intervention

• 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 Name: Tecentriq
• Drug: BTCT4465A (Mosunetuzumab) SC
  Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.

Study Arms

• 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.
  Interventions:

  • Drug: BTCT4465A (Mosunetuzumab) IV
  • Drug: Atezolizumab
  • Drug: BTCT4465A (Mosunetuzumab) SC
• Experimental: Dose Expansion
  Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.
  Interventions:

  • Drug: BTCT4465A (Mosunetuzumab) IV
  • Drug: Atezolizumab
  • Drug: BTCT4465A (Mosunetuzumab) SC

Publications *

• Budde LE, Sehn LH, Matasar M, Schuster SJ, Assouline S, Giri P, Kuruvilla J, Canales M, Dietrich S, Fay K, Ku M, Nastoupil L, Cheah CY, Wei MC, Yin S, Li CC, Huang H, Kwan A, Penuel E, Bartlett NL. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022 Aug;23(8):1055-1065. doi: 10.1016/S1470-2045(22)00335-7. Epub 2022 Jul 5.
• Budde LE, Assouline S, Sehn LH, Schuster SJ, Yoon SS, Yoon DH, Matasar MJ, Bosch F, Kim WS, Nastoupil LJ, Flinn IW, Shadman M, Diefenbach C, O'Hear C, Huang H, Kwan A, Li CC, Piccione EC, Wei MC, Yin S, Bartlett NL. Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. J Clin Oncol. 2022 Feb 10;40(5):481-491. doi: 10.1200/JCO.21.00931. Epub 2021 Dec 16.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 14, 2021): 836
• Original Estimated Enrollment (submitted: July 14, 2015): 170
• Estimated Study Completion Date: November 15, 2023
• Estimated Primary Completion Date: November 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Germany, Korea, Republic of, Spain, United Kingdom, United States
• Removed Location Countries: France

Administrative Information

• NCT Number: NCT02500407
• Other Study ID Numbers: GO29781
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: May 2023