This phase II trial tests how well pirtobrutinib and mosunetuzumab work in treating patients with grade 1-3a follicular lymphoma (FL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Pirtobrutinib, a type of tyrosine kinase inhibitor, works by blocking the action of the Bruton tyrosine kinase (BTK) protein. The BTK protein signals cancer cells to multiply, and blocking it may help keep cancer cells from growing. It could also improve T cell fitness and decrease inflammation, therefore, may improve the efficacy and safety of T cell-based therapies, such as mosunetuzumab. Mosunetuzumab is a bispecific antibody that binds both T cells and the lymphoma cancer cells and harnesses T cells to interfere with the ability of cancer cells to grow and spread. Giving pirtobrutinib and mosunetuzumab together may kill more tumor cells in patients with relapsed or refractory grade 1-3a FL and potentially decreases some side effects of mosunetuzumab which are related to T cells being activated (e.g., cytokine release syndrome).
Ability to understand, willing, and capable of signing a written informed consent document
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Histologically confirmed FL, grades 1-3a
Prior BTK inhibitor (BTKi) refractory disease defined as disease progression or recurrence during or within 6 months of prior BTKi therapy. If disease progression or recurrence occurs > 6 months after patients are off BTKi (e.g., due to intolerance), it is not considered as BTKi refractoriness. Patients with prior BTKi exposure but not meeting the criteria of BTKi refractoriness can be enrolled in this trial
Prior exposure to pirtobrutinib
CD3 T-cell engager exposed disease. However, these patients may be eligible if they stay in remission for at least 24 months after the last treatment with CD3 T-cell engager and have histologically confirmed CD20 expression on lymphoma at relapse or progression of disease
Prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate within 4 weeks before first pirtobrutinib administration
Single group
Pirtobrutinib
DrugGiven PO
Mosunetuzumab
Biological/VaccineGiven SC or IV
Biospecimen Collection
Procedure/SurgeryUndergo blood sample and oral swab and/or rectal swab collection
Biopsy Procedure
Procedure/SurgeryUndergo tissue biopsy
Computed Tomography
Procedure/SurgeryUndergo CT and PET/CT
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Questionnaire Administration
Other interventionAncillary studies
Complete remission (CR) rate
Will report the number of CR and the estimated CR rate with 95% exact binomial confidence interval (CI). Will build logistic regression to evaluate the risk factor association with the endpoint of interest.
Progression free survival (PFS)
Analyses will follow standard methodology by employing Kaplan-Meier (KM) and Cox proportional hazard model methodology. The 1-year PFS rate and 95% CI will be estimated by KM.
Cytokine release syndrome (CRS)
CRS will be graded by the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading system. The rate and grade of CRS will be reported.
Immune effector cell-associated neurotoxicity syndrome (ICANS)
ICANS will be graded by the ASTCT Consensus Grading system. Will report the rate and grade of ICANS.
Incidence of grade 3 or higher adverse events (AEs)
AEs will be graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Overall survival
Analyses will follow standard methodology by employing KM and Cox proportional hazard model methodology.
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University of Washington
Lead sponsor
Eli Lilly and Company
Collaborator
