Pirtobrutinib and Mosunetuzumab for the Treatment of Relapsed/Refractory Grades 1-3A Follicular Lymphoma, PROMOTE-FL Trial

Inclusion Criteria: * 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 * Relapsed after or failed to respond to at least two prior lines of systemic therapy and had received prior treatment with an anti-CD20-directed therapy * Prior treatment-related adverse events (AEs) must have recovered to grade ≤ 1 with the exception of alopecia and grade 2 peripheral neuropathy * At least one bi-dimensionally measurable lesion (≥ 1.5 cm in its largest dimension for nodal lesions, or ≥ 1.0 cm in its largest dimension for extranodal lesions within 6 weeks of screening by PET/CT scans with diagnostic computed tomography \[CT\] scan. PET/magnetic resonance imaging \[MRI\] scans may be allowed only if they are approved by the principal investigator \[PI\]) * Aspartate aminotransferase and alanine aminotransferase ≤ 3 x the upper limit of normal (ULN) * Total bilirubin ≤ 1.5 x ULN; or total bilirubin ≤ 3 x ULN in patients with documented liver involvement or in patients with a documented history of Gilbert syndrome * Platelet count ≥ 75 000/mm\^3 at any time during the screening window without requiring transfusion within 14 days prior to first dose of pirtobrutinib * Absolute neutrophil count ≥ 1000/mm\^3 in the absence of growth factor support * Total hemoglobin ≥ 10 g/dL at any time during the screening window without requiring transfusion within 21 days prior to first dose of pirtobrutinib * Patients who did not meet criteria for hematologic function because of extensive marrow involvement of non-Hodgkin lymphoma, splenic sequestration, and/or disease-related cytopenia (e.g., immune thrombocytopenia) could be enrolled into the study if they have platelet count ≥ 50,000/mm\^3, absolute neutrophil count ≥ 750/mm\^3, and hemoglobin ≥ 7.5 g/dL after discussion with and confirmation by the PI * Activated partial thromboplastin time (or partial thromboplastin time) and prothrombin (or international normalized ratio) ≤ 1.5 ULN * Estimated creatinine clearance (CL) ≥ 30 mL/min by Cockcroft-Gault formula: (140 - age) x body weight (kg) x 0.85 (if female) serum creatinine (mg/dl) x 72 or other institutional standard methods (e.g., based on nuclear medicine renal scan) * Negative serum pregnancy test at any time during the screening window for women of childbearing potential (WOCBP), defined as following: menarche and who are not postmenopausal (and 2 years of non-therapy-induced amenorrhea) or surgically sterile. Additionally, a negative serum pregnancy test is required within 3 days of initiating pirto * Fertile male and WOCBP patients must be willing to use highly effective contraceptive methods from the initiation of study treatment, until at least 3 months after the last dose of mosun or at least one month after the last dose of pirto, whichever occurs last Exclusion Criteria: * 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 * Prior treatment with systemic immunotherapeutic agents for which the mechanism of action involves T cells, including but not limited to cytokine therapy and anti-CTLA-4, anti-programmed death (PD)-1 and anti-PD-ligand 1 therapeutic antibodies, within 12 weeks or 5 half-lives of the drug, whichever was shorter, before first pirtobrutinib administration * Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever was shorter, prior to first pirtobrutinib administration * Treatment with radiotherapy within 2 weeks prior to the first pirtobrutinib administration. If patients received radiotherapy within 4 weeks prior to the first pirtobrutinib administration, patients must have had at least one measurable lesion outside of the radiation field. Patients who had only one measurable lesion that was previously irradiated but subsequently progressed are eligible * History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within 60 days of enrollment or presence of any of the following, regardless of prior SCT and/or CAR-T therapy timing: * Active graft versus host disease (GVHD); * Cytopenia from incomplete blood cell count recovery post-transplant; * Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity \> grade 1 from CAR-T therapy; * Ongoing immunosuppressive therapy (\> 20 mg prednisone or equivalent daily) or have been off immunosuppressive agents \< 2 months * Prior solid organ transplantation * Patients who cannot swallow oral medications * History of bleeding diathesis * Patients who experienced a major bleeding event on prior treatment with a BTKi * Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug * History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, infla