A Study Evaluating the Safety and Efficacy of Glofitamab or Mosunetuzumab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT04313608

Collaborator

(none)

Enrollment

Locations

Arms

16.7

Actual Duration (Months)

7.7

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate the safety and efficacy of glofitamab or mosunetuzumab in combination with gemcitabine and oxaliplatin (Glofit-GemOx or Mosun-GemOx) in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL).

Condition or Disease	Intervention/Treatment	Phase
B-cell Lymphoma	Drug: Glofitamab Drug: Gemcitabine Drug: Oxaliplatin Drug: Mosunetuzumab Drug: Obinutuzumab Drug: Tocilizumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Glofitamab or Mosunetuzumab in Combination With Gemcitabine Plus Oxaliplatin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

Actual Study Start Date :

Jun 4, 2020

Actual Primary Completion Date :

Oct 26, 2021

Actual Study Completion Date :

Oct 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Glofit-GemOx Participants will receive up to 8 cycles of Glofit-GemOx (glofitamab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles, followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab.	Drug: Glofitamab Participants will receive intravenous (IV) glofitamab in combination with gemcitabine and oxaliplatin for up to 8 cycles, followed by up to 4 cycles of glofitamab monotherapy. Other Names: RO7082859 Drug: Gemcitabine Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles. Drug: Oxaliplatin Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles. Drug: Obinutuzumab Participants will receive a single dose of IV obinutuzumab 7 days prior to the first administration of glofitamab. Other Names: RO5072759 Drug: Tocilizumab Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS). Other Names: RO4877533
Experimental: Arm B: Mosun-GemOx Participants will receive up to 8 cycles of Mosun-GemOx (mosunetuzumab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles.	Drug: Gemcitabine Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles. Drug: Oxaliplatin Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles. Drug: Mosunetuzumab Participants will receive IV mosunetuzumab in combination with gemcitabine and oxaliplatin for up to 8 cycles. Other Names: RO7030816 Drug: Tocilizumab Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS). Other Names: RO4877533

Arm

Intervention/Treatment

Experimental: Arm A: Glofit-GemOx

Participants will receive up to 8 cycles of Glofit-GemOx (glofitamab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles, followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab.

Drug: Glofitamab

Participants will receive intravenous (IV) glofitamab in combination with gemcitabine and oxaliplatin for up to 8 cycles, followed by up to 4 cycles of glofitamab monotherapy.

Other Names:

RO7082859

Drug: Gemcitabine

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Drug: Oxaliplatin

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Drug: Obinutuzumab

Participants will receive a single dose of IV obinutuzumab 7 days prior to the first administration of glofitamab.

Other Names:

RO5072759

Drug: Tocilizumab

Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).

Other Names:

RO4877533

Experimental: Arm B: Mosun-GemOx

Participants will receive up to 8 cycles of Mosun-GemOx (mosunetuzumab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles.

Drug: Gemcitabine

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Drug: Oxaliplatin

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Drug: Mosunetuzumab

Participants will receive IV mosunetuzumab in combination with gemcitabine and oxaliplatin for up to 8 cycles.

Other Names:

RO7030816

Drug: Tocilizumab

Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).

Other Names:

RO4877533

Outcome Measures

Primary Outcome Measures

Percentage of Participants with Adverse Events (AEs) [Up to 17 months]

Secondary Outcome Measures

Tolerability of Study Treatment as Measured by Dose Interruptions, Dose Reductions, Dose Intensity, and Treatment Discontinuation due to AEs [Up to 17 months]
Complete Response (CR) Based on PET/CT as Determined by the Investigator According to the 2014 Lugano Response Criteria [Up to 17 months]
Objective Response Rate (ORR), Defined as the Proportion of Participants with a Best Overall Response of Partial Response (PR) or CR, as Determined by the Investigator According to the 2014 Lugano Response Criteria [Up to 17 months]
Minimum Serum Concentration (Cmin) of the CD20-CD3 Bispecific Antibody [At pre-defined intervals from baseline up to 17 months]
Maximum Serum Concentration (Cmax) of the CD20-CD3 Bispecific Antibody [At pre-defined intervals from baseline up to 17 months]
Area Under the Concentration-Time Curve (AUC) of the CD20-CD3 Bispecific Antibody [At pre-defined intervals from baseline up to 17 months]
Proportion of Participants with Anti-Drug Antibodies (ADAs) to Glofitamab [Baseline up to 17 months]
Proportion of Participants with ADAs to Mosunetuzumab [Baseline up to 17 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0,1, or 2
Histologically confirmed B-cell lymphoma, including one of the following diagnoses per the 2016 World Health Organization (WHO) classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS); HGBCL with MYC and BCL2 and/or BCL6 rearrangements; HGBCL, NOS
R/R disease, defined as follows: Relapse: disease that has recurred following a response that lasted >/=6 months after completion of last line of therapy; Refractory: disease that progressed during therapy or progressed within 6 months (<6 months) of prior therapy
At least one line of prior systemic therapy
At least one bi-dimensionally measurable nodal lesion or one bi-dimensionally measurable extranodal lesion, as measured on positron emission tomography-computed tomography (PET/CT) scan
Adequate hematologic function
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as follows: Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 18 months after the final dose of obinutuzumab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, 3 months after the final dose of mosunetuzumab, 3 months after the final dose of tocilizumab, and 2 months after the final dose of glofitamab. Women must refrain from donating eggs during this same period
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as follows: With a female partner of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 2 months after the final dose of glofitamab, 2 months after the final dose of mosunetuzumab, 2 months after the final dose of tocilizumab (if applicable), 3 months after the final dose of obinutuzumab, and 6 months after the final dose of oxaliplatin or gemcitabine to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

Exclusion Criteria

Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
Contraindication to obinutuzumab, gemcitabine, oxaliplatin, or tocilizumab
Prior treatment with a bispecific antibody targeting both CD20 and CD3, including glofitamab and mosunetuzumab
Grade >1 peripheral neuropathy
Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to the first study treatment
Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
History of other malignancy that could affect compliance with the protocol or interpretation of results
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to first study treatment
Suspected or latent tuberculosis
Positive test results for chronic hepatitis B virus (HBV) infection
Positive test results for hepatitis C virus (HCV) antibody
Known HIV-seropositive status
Known or suspected chronic active Epstein-Barr virus infection
Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
History of progressive multifocal leukoencephalopathy
Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
Administration of a live, attenuated vaccine within 4 weeks prior to the first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
Prior solid organ transplantation
Prior allogenic stem cell transplant
Active autoimmune disease requiring treatment
Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks prior to the first dose of study treatment
Corticosteroid therapy within 2 weeks prior to first dose of study treatment, with exceptions defined by the study protocol
Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
Clinically significant history of liver disease, including cirrhosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Prince of Wales Hospital; Haematology	Randwick	New South Wales	Australia	2031
2	Monash Health Monash Medical Centre	Clayton	Victoria	Australia	3168
3	St Vincent's Hospital Melbourne	Fitzroy	Victoria	Australia	3065