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

Follicular Lymphoma Clinical Trial

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 Follicular Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04246086
• Other study ID #: CO41942
• Secondary ID: 2019-004291-20
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 12, 2020
• Est. completion date: November 15, 2027

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 187
• Est. completion date: November 15, 2027
• Est. primary completion date: November 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Mosunetuzumab (IV)
Participants will receive IV mosunetuzumab as defined by the study protocol
• Tocilizumab
Participants will receive IV tocilizumab as needed for adverse reactions as defined by the study protocol
• Lenalidomide
Participants will receive oral lenalidomide as defined by the study protocol
• Mosunetuzumab (SC)
Participants will receive SC mosunetuzumab as defined by the study protocol

Locations

Country	Name	City	State
China	the First Hospital of Jilin University	Changchun
China	Hunan Cancer Hospital	Changsha CITY
China	West China Hospital, Sichuan University	Chengdu
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	The First Affiliated Hospital of Xiamen University	Xiamen
France	CHRU de Lille - Hopital Claude Huriez	Lille
France	CHU Montpellier	Montpellier
France	Hôpital Saint-Louis	Paris
France	Centre Hospitalier Lyon Sud; Direction Générale	Pierre Benite
France	CHU Rennes - Hopital Pontchaillou	Rennes cedex 09
France	Institut Claudius Regaud; IUCT Oncopôle	Toulouse
Spain	Hospital Universitario Vall d Hebron	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz.	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Complejo Asistencial Universitario de Salamanca	Salamanca
United Kingdom	University College London Hospitals NHS Foundation Trust - University College Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Freeman Hospital	Newcastle upon Tyne
United Kingdom	Nottingham University Hospitals NHS Trust - City Hospital	Nottingham
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United States	City of Hope National Medical Center	Duarte	California
United States	Swedish Medical Center; IDS Pharmacy	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  China,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Limiting Toxicities (DLTs)		Cycle 2 Days 1-28 (cycle length = 28 days)
Primary	Percentage of Participants with Adverse Events		From baseline to 90 days after the last dose of study drug
Primary	Cumulative Area under the Curve over Cycles 1-3 (AUC1-3) of Mosunetuzumab		Day 1 - Day 78
Primary	Serum Trough Concentration at Steady State Approximated by Cycle 4 (Ctrough, c4) of Mosunetuzumab		Day 106
Secondary	Complete Response Rate (CRR) as determined by the investigator (non-randomized stage)		Up to the end of Cycle 12 (cycle length = 28 days)
Secondary	CRR as determined by Independent Review Committee (IRC) (randomized stage)		Up to the end of Cycle 12 (cycle length = 28 days)
Secondary	Objective Response Rate (ORR) as determined by the investigator (non-randomized stage)		Up to the end of Cycle 12 (cycle length = 28 days)
Secondary	ORR as determined by IRC (randomized stage)		Up to the end of Cycle 12 (cycle length = 28 days)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Minimum Serum Concentration (Cmin) of Mosunetuzumab		At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Secondary	Maximum Serum Concentration (Cmax) of Mosunetuzumab		At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Secondary	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)
Secondary	Percentage of Participants with ADAs to Mosunetuzumab		At pre-defined intervals from baseline through follow-up (2 years after last treatment)
Secondary	Percentage of Participants with AEs (Arms A and B)		From baseline to 90 days after the last dose of study drug
Secondary	Cumulative AUC Over Cycles 1-2 (AUCc1-2) of Mosunetuzumab (Arms A and B)		Day 1 - Day 50
Secondary	Serum Trough Concentration in Cycle 2 (Ctrough, c2) of Mosunetuzumab (Arms A and B)		Day 50
Secondary	AUC at Steady State (AUCss) (Arms A and B)		Cycle 4 (cycle length = 28 days)