A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide (+Len), and the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Participants With Follicular Lymphoma

A Phase Ib/II, Open-Label, Multicenter Study With a Non-Randomized Stage Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab Plus Lenalidomide (+Len), and a Randomized Stage Evaluating the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Patients With Follicular Lymphoma

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab (Mosun) + lenalidomide (Len) (Mosun + Len) in participants with follicular lymphoma (FL). This study will also compare the pharmacokinetics, pharmacodynamics, safety, efficacy, and immunogenicity of IV mosunetuzumab + len vs subcutaneous (SC) mosunetuzumab + len.

Study Overview

• Status: Active, not recruiting
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Drug: Mosunetuzumab (IV); Drug: Tocilizumab; Drug: Lenalidomide; Drug: Mosunetuzumab (SC)

• Study Type: Interventional
• Enrollment (Estimated): 187
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: CO41942 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• China
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changsha CITY, China, 410013
    • Hunan Cancer Hospital
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Tianjin, China, 3000060
    • Tianjin Medical University Cancer Institute & Hospital
  • Xiamen, China, 361003
    • The First Affiliated Hospital of Xiamen University
• France
  • Lille, France, 59037
    • CHRU de Lille - Hopital Claude Huriez
  • Montpellier, France, 34295
    • CHU Montpellier
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud; Direction Générale
  • Rennes cedex 09, France, 35033
    • CHU Rennes - Hopital Pontchaillou
  • Toulouse, France, 31059
    • Institut Claudius Regaud; IUCT Oncopôle
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d Hebron
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz.
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust - University College Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust - City Hospital
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospitals NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center; IDS Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• R/R FL after treatment with at least one prior systemic lymphoma therapy, which includes prior immunotherapy or chemoimmunotherapy
• Previously untreated participants with FL must require systemic therapy assessed by investigator based on the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
• Histologically documented FL of Grade 1, 2, or 3a, and that expresses CD20 at time of diagnosis as determined by the local laboratory
• Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive lymphoma)
• At least one bi dimensionally measurable nodal lesion (>1.5 cm in its largest dimension by PET- computed tomography (CT) scan), or at least one bi dimensionally measurable extranodal lesion (>1.0 cm in its largest dimension by PET-CT scan)
• Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of FL
• Adequate hematologic function (unless due to underlying lymphoma, per the investigator) as defined by the protocol
• Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/mL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
• Normal laboratory values (unless due to underlying lymphoma) as defined by the protocol
• Agreement to comply with all local requirements of the Len risk minimization plan
• For women of childbearing potential: agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period, and for at least 12 months after the final dose of glofitamab, 28 days after the last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun. Women must refrain from donating eggs during this same period
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm, with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 2 months after the final dose of glofitamab, 28 days after last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun

Exclusion Criteria

• Any history of Grade 3b FL
• Any history of disease transformation and/or diffuse large B-cell lymphoma (DLBCL)
• Documented refractoriness to an obinutuzumab monotherapy containing regimen in glofitamab-containing treatment combination
• Active or history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
• Documented refractoriness to lenalidomide, defined as no response (partial response (PR) or complete response (CR)) within 6 months of therapy
• Prior standard or investigational anti-cancer therapy as specified by the protocol
• Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade <=2 prior to Day 1 of Cycle 1
• Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT scan
• Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
• History of solid organ transplantation
• History of severe allergic or anaphylactic reaction to humanized, chimeric or murine MAbs
• Known sensitivity or allergy to murine products
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the glofitamab, Mosun, G, Len, or thalidomide formulation, including mannitol
• History of erythema multiforme, Grade >=3 rash, or blistering following prior treatment with immunomodulatory derivatives
• Known history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT scan
• Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
• Known or suspected chronic active Epstein-Barr virus infection or hemophagocytic syndrome
• Known history of macrophage activating syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH)
• Active Hepatitis B and Hepatitis C infection or autoimmune disease requiring treatment
• Prior allogenic hematopoietic stem cell transplant
• Known history of HIV positive status
• History of progressive multifocal leukoencephalopathy
• Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
• Other malignancy that could affect compliance with the protocol or interpretation of results
• Prior allogenic hematopoietic stem cell transplant (HSCT)
• Contraindication to treatment for thromboembolism prophylaxis
• Grade >=2 neuropathy
• Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to significant cardiovascular disease or significant pulmonary disease
• Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Inadequate hematologic function
• Any of the following abnormal laboratory values
• Pregnant or lactating or intending to become pregnant during the study
• Life expectancy < 3 months
• Unable to comply with the study protocol, in the investigator's judgment
• History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's or Medical Monitor's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous (IV) Mosunetuzumab + Lenalidomide (Non-randomized); Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)	Drug: Mosunetuzumab (IV); Participants will receive IV mosunetuzumab as defined by the study protocol; Other Names: RO7030816; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed for adverse reactions as defined by the study protocol; Other Names: RO4877533; Drug: Lenalidomide; Participants will receive oral lenalidomide as defined by the study protocol
Experimental: Arm A: IV Mosunetuzumab + Len (Randomized); Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)	Drug: Mosunetuzumab (IV); Participants will receive IV mosunetuzumab as defined by the study protocol; Other Names: RO7030816; Drug: Lenalidomide; Participants will receive oral lenalidomide as defined by the study protocol
Experimental: Arm B: SC Mosunetuzumab + Len (Randomized); Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)	Drug: Lenalidomide; Participants will receive oral lenalidomide as defined by the study protocol; Drug: Mosunetuzumab (SC); Participants will receive SC mosunetuzumab as defined by the study protocol; Other Names: RO7030816
Experimental: Subcutaneous (SC) Mosunetuzumab + Lenalidomide (Non-randomized); Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward). Participants that have received complete metabolic response (CMR) or partial metabolic response (PMR) after 12 cycles of induction therapy with mosunetuzumab + lenalidomide will have the option of receiving maintenance therapy with SC mosunetuzumab every 8 weeks (Q8W) for an additional 9 cycles.	Drug: Tocilizumab; Participants will receive IV tocilizumab as needed for adverse reactions as defined by the study protocol; Other Names: RO4877533; Drug: Lenalidomide; Participants will receive oral lenalidomide as defined by the study protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-Limiting Toxicities (DLTs)	Cycle 2 Days 1-28 (cycle length = 28 days)
Percentage of Participants with Adverse Events	From baseline to 90 days after the last dose of study drug
Cumulative Area under the Curve over Cycles 1-3 (AUC1-3) of Mosunetuzumab	Day 1 - Day 78
Serum Trough Concentration at Steady State Approximated by Cycle 4 (Ctrough, c4) of Mosunetuzumab	Day 106

Secondary Outcome Measures

Outcome Measure	Time Frame
Minimum Serum Concentration (Cmin) of Mosunetuzumab	At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Maximum Serum Concentration (Cmax) of Mosunetuzumab	At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Area Under the Concentration vs Time Curve (AUC) of Mosunetuzumab	At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Percentage of Participants with ADAs to Mosunetuzumab	At pre-defined intervals from baseline through follow-up (2 years after last treatment)
Percentage of Participants with AEs (Arms A and B)	From baseline to 90 days after the last dose of study drug
Cumulative AUC Over Cycles 1-2 (AUCc1-2) of Mosunetuzumab (Arms A and B)	Day 1 - Day 50
Serum Trough Concentration in Cycle 2 (Ctrough, c2) of Mosunetuzumab (Arms A and B)	Day 50
AUC at Steady State (AUCss) (Arms A and B)	Cycle 4 (cycle length = 28 days)
Complete Response Rate (CRR) as determined by the investigator (non-randomized stage)	Up to the end of Cycle 12 (cycle length = 28 days)
CRR as determined by Independent Review Committee (IRC) (randomized stage)	Up to the end of Cycle 12 (cycle length = 28 days)
Objective Response Rate (ORR) as determined by the investigator (non-randomized stage)	Up to the end of Cycle 12 (cycle length = 28 days)
ORR as determined by IRC (randomized stage)	Up to the end of Cycle 12 (cycle length = 28 days)
Duration of Response (DOR) as determined by the investigator (non-randomized stage)	From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, up to the end of Cycle 8 (cycle length = 28 days)
DOR as determined by IRC (randomized stage)	From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, up to the end of Cycle 8 (cycle length = 28 days)
Duration of Complete Reponse (DOCR) as determined by the investigator (non-randomized stage)	From the first occurrence of a documented complete response (CR) to disease progression, relapse, or death from any cause, whichever occurs first, up to the end of Cycle 12 (cycle length = 28 days)
DOCR as determined by IRC (randomized stage)	From the first occurrence of a documented complete response (CR) to disease progression, relapse, or death from any cause, whichever occurs first, up to the end of Cycle 12 (cycle length = 28 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2020
• Primary Completion (Actual): February 1, 2024
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: CO41942; 2019-004291-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No