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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 R/R Follicular Lymphoma

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04246086
Collaborator
(none)
169
Enrollment
22
Locations
4
Arms
67.6
Anticipated Duration (Months)
7.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
169 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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 Relapsed or Refractory Follicular Lymphoma
Actual Study Start Date :
Aug 12, 2020
Anticipated Primary Completion Date :
Mar 29, 2024
Anticipated Study Completion Date :
Mar 31, 2026

Arms and Interventions

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: 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)

    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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose-Limiting Toxicities (DLTs) [Cycle 2 Days 1-28 (cycle length = 28 days)]

    2. Percentage of Participants with Adverse Events [From baseline to 90 days after the last dose of study drug]

    3. Cumulative Area under the Curve over Cycles 1-3 (AUC1-3) of Mosunetuzumab [Day 1 - Day 78]

    4. Serum Trough Concentration at Steady State Approximated by Cycle 4 (Ctrough, c4) of Mosunetuzumab [Day 106]

    Secondary Outcome Measures

    1. Complete Response Rate (CRR) [Up to the end of Cycle 12 (cycle length = 28 days)]

    2. Objective Response Rate (ORR) [Up to the end of Cycle 12 (cycle length = 28 days)]

    3. Duration of Response (DOR) [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)]

    4. Duration of Complete Reponse (DOCR) [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)]

    5. Minimum Serum Concentration (Cmin) of Mosunetuzumab [At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)]

    6. Maximum Serum Concentration (Cmax) of Mosunetuzumab [At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)]

    7. 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)]

    8. Percentage of Participants with ADAs to Mosunetuzumab [At pre-defined intervals from baseline through follow-up (2 years after last treatment)]

    9. Percentage of Participants with AEs (Arms A and B) [From baseline to 90 days after the last dose of study drug]

    10. Cumulative AUC Over Cycles 1-2 (AUCc1-2) of Mosunetuzumab (Arms A and B) [Day 1 - Day 50]

    11. Serum Trough Concentration in Cycle 2 (Ctrough, c2) of Mosunetuzumab (Arms A and B) [Day 50]

    12. AUC at Steady State (AUCss) (Arms A and B) [Cycle 4 (cycle length = 28 days)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

    • R/R FL after treatment with at least one prior chemo immunotherapy regimen that included an anti CD20 monoclonal antibody (MAb)

    • 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

    • 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 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope National Medical Center Duarte California United States 91010
    2 Swedish Medical Center; IDS Pharmacy Seattle Washington United States 98122
    3 the First Hospital of Jilin University Changchun China 130021
    4 Hunan Cancer Hospital GCP Pharmacy Changsha China 410013
    5 West China Hospital, Sichuan University Chengdu China 610041
    6 Fudan University Shanghai Cancer Center Shanghai City China 200120
    7 Tianjin Medical University Cancer Institute & Hospital Tianjing China 300060
    8 CHRU de Lille - Hopital Claude Huriez Lille France 59037
    9 CHU Montpellier Montpellier France 34295
    10 Hôpital Saint-Louis Paris France 75475
    11 Centre Hospitalier Lyon Sud; Direction Générale Pierre Benite France 69495
    12 CHU Rennes - Hopital Pontchaillou Rennes cedex 09 France 35033
    13 Institut Claudius Regaud; IUCT Oncopôle Toulouse France 31059
    14 Hospital Universitario Vall d'Hebron Barcelona Spain 08035
    15 Hospital Universitario Fundacion Jimenez Diaz. Madrid Spain 28040
    16 Hospital Universitario Virgen de la Victoria Malaga Spain 29010
    17 Complejo Asistencial Universitario de Salamanca Salamanca Spain 37007
    18 University College London Hospitals NHS Foundation Trust - University College Hospital London United Kingdom NW1 2PG
    19 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
    20 Freeman Hospital Newcastle upon Tyne United Kingdom NE7 7DN
    21 Nottingham University Hospitals NHS Trust - City Hospital Nottingham United Kingdom NG5 1PB
    22 Oxford University Hospitals NHS Foundation Trust Oxford United Kingdom OX3 7LE

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04246086
    Other Study ID Numbers:
    • CO41942
    • 2019-004291-20
    First Posted:
    Jan 29, 2020
    Last Update Posted:
    Aug 11, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Follicular
    Lenalidomide

    Study Results

    No Results Posted as of Aug 11, 2022