A Phase II Study Evaluating the Efficacy of Mosunetuzumab in Combination With Polatuzumab Vedotin in Untreated Follicular Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Mosunetuzumab
- Conditions
- Lymphoma, Follicular
- Sponsor
- Washington University School of Medicine
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Number of participants with complete response (CR) as best response
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This phase II clinical trial studies the combination of mosunetuzumab and polatuzumab vedotin in order to see how well it works in patients with untreated follicular lymphoma. Mosunetuzumab is an antibody that has been engineered to attach to two target cells in the immune system: T cells that normally perform tasks like killing virus-infected cells, and cancerous B cells. Mosunetuzumab has been designed to direct these T cells to kill the cancerous B cells instead. Polatuzumab vedotin is an antibody-drug conjugate that attaches to certain cancerous B cells and then delivers a drug specifically to those cells.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of follicular lymphoma grade 1-3A, stage II-IV by Ann Arbor criteria.
- •One or more of the following criteria (adapted from GELF criteria):
- •Any nodal or extranodal tumor mass with diameter \> 7 cm
- •Involvement of at least 3 nodal sites, each with diameter \> 3 cm
- •Presence of any systemic or B symptoms
- •Splenic enlargement with inferior margin below the umbilical line
- •Compression syndrome (e.g., ureteral, orbital, gastrointestinal)
- •Pleural or peritoneal serous effusion (irrespective of cell content)
- •Cytopenia(s) attributable to lymphoma
- •At least 18 years of age.
Exclusion Criteria
- •Prior history of aggressive B cell lymphoma such as diffuse large B cell lymphoma or high-grade B cell lymphoma.
- •Known history of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents.
- •Known history of macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH).
- •Current or past history of CNS lymphoma.
- •Any prior systemic therapy for follicular lymphoma.
- •Treatment with radiotherapy within 2 weeks prior to the first dose of mosunetuzumab (otherwise one measurable lesion outside of the radiation field must remain).
- •Treatment with any anti-CD20 monoclonal antibody within 4 weeks of Day 1 of Cycle
- •Current or recent history (within the last 6 months) of CNS disease, such as stroke, epilepsy CNS vasculitis, or serious progressive neurodegenerative disease, with clinically significant symptoms.
- •Treatment with systemic immunosuppressive medications, including but not limited to prednisone (\> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle
- •\* Note: The use of inhaled corticosteroids, mineralocorticoids for management of orthostatic hypotension, and single dose dexamethasone for nausea or B symptoms is permitted.
Arms & Interventions
Mosunetuzumab and Polatuzumab Vedotin
Patients receive CD3xCD20 bispecific antibody mosunetuzumab administered subcutaneously in combination with CD79b directed ADC polatuzumab vedotin administered intravenously. Mosunetuzumab and polatuzumab vedotin are given in combination for 6 cycles. Mosunetuzumab is given on Days 1, 8, and 15 of cycle 1 and then Day 1 thereafter, and polatuzumab vedotin is given on Day 1. After 6 cycles, patients continue on mosunetuzumab alone for 2 additional cycles. Patients undergo scans at the end of cycle 8, and if those scans show a complete response, patients will stop any further treatment and will enter follow-up. Patients with a partial response or stable disease on scans at the end of cycle 8 may receive up to 9 additional cycles of mosunetuzumab in the absence of disease progression or unacceptable toxicity. All cycles are planned to be 21 days.
Intervention: Mosunetuzumab
Mosunetuzumab and Polatuzumab Vedotin
Patients receive CD3xCD20 bispecific antibody mosunetuzumab administered subcutaneously in combination with CD79b directed ADC polatuzumab vedotin administered intravenously. Mosunetuzumab and polatuzumab vedotin are given in combination for 6 cycles. Mosunetuzumab is given on Days 1, 8, and 15 of cycle 1 and then Day 1 thereafter, and polatuzumab vedotin is given on Day 1. After 6 cycles, patients continue on mosunetuzumab alone for 2 additional cycles. Patients undergo scans at the end of cycle 8, and if those scans show a complete response, patients will stop any further treatment and will enter follow-up. Patients with a partial response or stable disease on scans at the end of cycle 8 may receive up to 9 additional cycles of mosunetuzumab in the absence of disease progression or unacceptable toxicity. All cycles are planned to be 21 days.
Intervention: Polatuzumab vedotin
Outcomes
Primary Outcomes
Number of participants with complete response (CR) as best response
Time Frame: Through completion of treatment (estimated to be 1 year)
CR determined by response to treatment by PET-CT at end of treatment per Deauville 5-point scale (Lugano 2014 criteria). The Deauville scale is scored from 1 to 5, with 1 indicating no uptake on PET-CT and 5 indicating markedly increased uptake on PET-CT.
Secondary Outcomes
- Number of participants with stable disease (SD)(After Cycle 2 (each cycle is 21 days; estimated to be 42 days))
- Number of participants with complete response (CR)(After Cycle 2 (each cycle is 21 days; estimated to be 42 days))
- Time to first response of complete response (CR) or partial response (PR)(Through completion of treatment (estimated to be 1 year))
- Overall response rate (ORR) as measured by number of participants with complete response (CR) and partial response (PR)(After Cycle 2 (each cycle is 21 days; estimated to be 42 days))
- Overall survival (OS)(At 48 months)
- Time to first complete response (CR)(Through completion of treatment (estimated to be 1 year))
- Duration of first complete response (CR)(Through completion of treatment (estimated to be 1 year))
- Progression-free survival (PFS)(At 48 months)
- Rate of treatment discontinuation due to treatment-emergent adverse events (TEAEs)(Evaluated from start of treatment to 30 day follow-up after conclusion of treatment, study discontinuation/termination, or initiation of alternative lymphoma-directed therapy, whichever occurs first (estimated to be 1 year and 30 days).)
- Number of participants with partial response (PR)(After Cycle 2 (each cycle is 21 days; estimated to be 42 days))
- Time to next treatment (TTNT)(Through completion of follow-up (estimated to be 6 years))
- Number of tocilizumab doses per patient for management of cytokine release syndrome (CRS)(Up to approximately 1 year and 3 days)
- Number of participants with progressive disease (PD)(After Cycle 2 (each cycle is 21 days; estimated to be 42 days))
- Duration of first response of complete response (CR) or partial response (PR)(Through completion of treatment (estimated to be 1 year))
- Frequencies and grades of treatment-emergent adverse events (TEAEs)(Evaluated from start of treatment to 30 day follow-up after conclusion of treatment, study discontinuation/termination, or initiation of alternative lymphoma-directed therapy, whichever occurs first (estimated to be 1 year and 30 days).)
- Percentage of patients requiring any tocilizumab doses for management of cytokine release syndrome (CRS)(Up to approximately 1 year and 3 days)