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

NCT06948786 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1125134NCI-2025-0270820877
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Follicular Lymphoma; Refractory Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  After cycle 8 of mosunetuzumab (cycle length = 21 days)

• 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.

  From trial enrollment to disease progression or death, whichever occurs first, assessed at 1 year

Secondary Outcomes (7)

• Cytokine release syndrome (CRS)

  Up to 30 days after last dose of study treatment

• Immune effector cell-associated neurotoxicity syndrome (ICANS)

  Up to 30 days after last dose of study treatment

• Incidence of grade 3 or higher adverse events (AEs)

  Up to 30 days after last dose of study treatment.

• Overall survival

  From trial enrollment to death from any cause, assessed up to 4 years

• Event free survival

  From trial enrollment to death from any cause, disease progression, needing the next line of therapy, whichever occurs first, assessed up to 4 years

Study Arms (1)

Treatment (pirtobrutinib, mosunetuzumab)

EXPERIMENTAL

Patients receive pirtobrutinib PO QD on 7 days prior to the start of mosunetuzumab (day -7) and continue it until up to 52 weeks. Patients receive mosunetuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 then on day 1 of remaining cycles. Cycles of mosunetuzumab repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients with a CR after cycle 8 discontinue mosunetuzumab. Patients also undergo blood sample and oral swab and/or rectal swab collection, tissue biopsy, CT, and PET/CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy at screening and after cycle 8.

Drug: Pirtobrutinib; Biological: Mosunetuzumab; Procedure: Biospecimen Collection; Procedure: Biopsy Procedure; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Other: Questionnaire Administration

Interventions

Pirtobrutinib DRUG

Given PO

Also known as: BTK Inhibitor LOXO-305, LOXO 305, Jaypirca, LY3527727

Treatment (pirtobrutinib, mosunetuzumab)

Mosunetuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A, BTCT-4465A, CD20/CD3 BiMAb BTCT4465A, Lunsumio, RG 7828, RG-7828

Treatment (pirtobrutinib, mosunetuzumab)

Biospecimen Collection PROCEDURE

Undergo blood sample and oral swab and/or rectal swab collection

Also known as: Biological Sample Collection

Treatment (pirtobrutinib, mosunetuzumab)

Biopsy Procedure PROCEDURE

Undergo tissue biopsy

Also known as: Bx

Treatment (pirtobrutinib, mosunetuzumab)

Computed Tomography PROCEDURE

Undergo CT and PET/CT

Also known as: CT Scan, CT, CAT Scan

Treatment (pirtobrutinib, mosunetuzumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: PET scan, PET

Treatment (pirtobrutinib, mosunetuzumab)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (pirtobrutinib, mosunetuzumab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (pirtobrutinib, mosunetuzumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (pirtobrutinib, mosunetuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 without 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 without 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

pirtobrutinib; Biopsy; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Mengyang Di, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mengyang Di, MD, PhD

CONTACT

206-606-2519; mydi@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: April 29, 2025
• Study Start: November 17, 2025
• Primary Completion (Estimated): July 31, 2031
• Study Completion (Estimated): July 31, 2031
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)