The purpose of this study is to determine how effective and safe the combination of glofitamab and obinutuzumab is in treating patients with Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL) who have not received other treatments for their lymphoma. The names of the study drugs involved in this study are: * Glofitamab (a type of immunotherapy) * Obinutuzumab (a type of immunotherapy)
This is an open-label, multicenter, phase II study to evaluate the efficacy and safety of obinutuzumab and glofitamab for patients with untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL). Obinutuzumab and Glofitamab use the immune system to target and attack cancer cells. The research study procedures include screening for eligibility, study treatment visits, bone marrow biopsies, blood tests, Computerized Tomography (CT) scans, and Positron Emission Tomography (PET) scans. The U.S. Food and Drug Administration (FDA) has not approved glofitamab as a treatment for any disease. The U.S. FDA has approved obinutuzumab in combination with chemotherapy for patients with follicular lymphoma. Participants will receive study treatment for approximately 9 months and will be followed for 10 years. It is expected that about 45-50 people will take part in this research study. Genentech and Roche are supporting this research study by providing the study drugs, glofitamab and obinutuzumab, and funding for the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Humanized glycoengineered type II anti-CD20 monoclonal antibody, via IV infusion.
T-cell bispecific humanized monoclonal antibody, via IV infusion.
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Columbia University Irving Medical Center
New York, New York, United States
Mount Sinai Medical Center
New York, New York, United States
End of Treatment (EOT) Complete Metabolic Response (CMR) Rate
EOT CMR rate defined as the proportion of participants achieving CR per PET/CT Lugano 2014 criteria (protocol appendix B) at the EOT assessment: PET-CT, score 1, 2, or 3 with or without a residual mass on a 5-point scale (5PS).
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days
Best Partial Metabolic Response (PMR) Rate
Best PMR rate defined as the proportion of participants achieving PR per Lugano 2014 criteria (protocol appendix B) ever on treatment: PET-CT Score 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size or on CT, ≥ 50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; no increase in non-measured lesions; spleen if enlarged must have regressed by \>50% in length beyond normal.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days
Best Complete Metabolic Response (CMR) Rate
Best CMR rate defined as the proportion of participants achieving CR per Lugano 2014 criteria (protocol appendix B) ever on treatment.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days
Best Objective Metabolic Response (OMR) Rate
Best OMR rate defined as the proportion of participants achieving CR or partial response (PR) per Lugano 2014 criteria (protocol appendix B) ever on treatment.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days
EOT Partial Metabolic Response (PMR) Rate
EOT PMR rate defined as the proportion of participants achieving PR per PET/CT Lugano 2014 criteria (protocol appendix B) at the EOT assessment: PET-CT Score 4 or 5 with reduced uptake compared with baseline and residual mass(es).
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days
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EOT Objective Metabolic Response (OMR) Rate
EOT OMR rate defined as the proportion of participants achieving CR or partial response (PR) per PET/CT Lugano 2014 criteria (protocol appendix B) at the EOT assessment.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days
2-year Duration of Response (DOR)
2-year DOR is a probability estimated using the Kaplan Meier method; DOR is defined as the time measurement criteria are met for CR or PR (whichever is first recorded) per Lugano 2014 criteria (protocol Appendix B) until the first date that recurrent or progressive disease is objectively documented, or death due to any cause. CR and PR participants without events reported are censored at the last disease evaluation.
Time frame: 2 years
2-year Duration of Complete Response (DOCR)
2-year DOCR is a probability estimated using the Kaplan Meier method; DOCR is defined as the time measurement criteria are met for CR per Lugano 2014 criteria (protocol Appendix B) until the first date that recurrent or progressive disease is objectively documented, or death due to any cause. CR participants without events reported are censored at the last disease evaluation.
Time frame: 2 years
2-year Progression-free Survival (PFS)
2-year PFS is a probability estimated using the Kaplan Meier method; PFS is defined as the duration of time from study entry to documented disease progression (PD) or death. PD defined by Lugano 2014 criteria (protocol Appendix B).
Time frame: 2 years
2-year Time-to-Next Treatment (TTNT)
2-y TTNT is a probability estimated using the Kaplan Meier method; TTNT is defined as the duration of time from the first dose of treatment until the time of initiation of new therapy, or censored at the date of last contact.
Time frame: 2 years
2-year Overall Survival (OS)
2-year OS is a probability estimated using the Kaplan-Meier method; OS is defined as the time from study entry to death, or censored at date last known alive.
Time frame: 2 years
Incidence of Histological Transformation
Histological transformation was defined as participants who have a biopsy showing diffuse large B-cell lymphoma (DLBCL). Incidence is the number of participants with histological transformation during or after treatment.
Time frame: up to 10 years
Number of Participants with Cytokine Release Syndrome (CRS) by Grade
All grade CRS AEs regardless of attribution based on American Society of Transplantation and Cellular Therapy \[ASTCT\] Consensus grading as reported on case report forms are counted and maximum grade tabulated. Incidence by grade is then tabulated as the number of participants ever experiencing maximum grade during the time of observation.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days + 30 days
Grade 3-5 Treatment-Related CRS Rate
All grade 3-5 CRS AEs with attribution of probably, possibly or definitely-related to treatment based on American Society of Transplantation and Cellular Therapy \[ASTCT\] Consensus grading as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 CRS AE of any type during the time of observation.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days + 30 days
Number of Participants with Neurotoxicity by Grade
All grade neurotoxicity AEs regardless of attribution based on CTCAEv5 as reported on case report forms are counted and maximum grade tabulated. Incidence by grade is then tabulated as the number of participants ever experiencing maximum grade during the time of observation.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days + 30 days
Grade 3-5 Treatment-Related Neurotoxicity Rate
All grade 3-5 neurotoxicity AEs with attribution of probably, possibly or definitely-related to treatment based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 neurotoxicity AE of any type during the time of observation.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days + 30 days
Grade 3-5 Toxicity Rate
All grade 3-5 AEs regardless of attribution based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one grade 3-5 AE of any type during the time of observation.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days + 30 days
Grade 3-5 Treatment-Related Toxicity Rate
All grade 3-5 AEs with attribution of probably, possibly or definitely-related to treatment based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days + 30 days
Grade 2-5 Treatment-Related Toxicity Rate
All grade 2-5 AEs with attribution of probably, possibly or definitely-related to treatment based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 2-5 AE of any type during the time of observation.
Time frame: (Cycle 1 = 36 days, cycle 2 - 12 = 21 days), up to 267 days + 30 days