Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

NCT06252675 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: 232516NCI-2024-00054
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests the safety and effectiveness of glofitamab given in combination with pirtobrutinib in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Glofitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Obinutuzumab may also reduce the risk of immune-related conditions from treatment. Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the protein that signals cancer cells to multiply. Giving glofitamab in combination with pirtobrutinib may be safe, tolerable and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (5)

• Percentage of participants with high grade, treatment-emergent adverse events (AEs)

  The severity of the toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. AEs and clinically significant laboratory abnormalities meeting grade 3 4 or 5 will be summarized by maximum intensity and relationship to study drug for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days.

  Approximately 2 weeks

• Proportion of participants with Complete Response (CR)

  CR will be defined as the proportion of treated participants who experience a CR per Lugano criteria among evaluable participants. The Lugano classification recommends the Deauville five-point scale for reporting response by Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT): (1) no uptake or no residual uptake (when used interim) (2) slight uptake, but below blood pool (mediastinum) (3) uptake above mediastinal, but below or equal to uptake in the liver (4) uptake slightly to moderately higher than liver (5) markedly increased uptake or any new lesion (on response evaluation) from cycle 5 Day 1 through the follow-up period up to 94 weeks.

  Up to 94 weeks

• Proportion of participants with reported Cytokine-release syndrome (CRS)

  The proportion of participants with a diagnosed incident of CRS for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.

  Approximately 2 weeks

• Proportion of participants with immune effector cell-associated neurotoxicity syndrome (ICANS)

  The proportion of participants with a diagnosed incident of ICANS for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.

  Approximately 2 weeks

• Proportion of participants with reported Hemophagocytic lymphohistiocytosis (HLH)

  The proportion of participants with a diagnosed incident of HLH for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.

  Approximately 2 weeks

Secondary Outcomes (7)

• Median Progression-free survival (PFS)

  Up to 94 weeks

• Median Overall Survival (OS)

  Up to 94 weeks

• Objective Response Rate (ORR)

  Up to 94 weeks

• Duration of response (DOR)

  Up to 94 weeks

• Proportion of participants with complete response without measurable disease (CRMRD)

  At cycle 13, day 1 (a cycle is 21 days)

Study Arms (1)

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

EXPERIMENTAL

Participants receive obinutuzumab IV on days 1 and 2 of cycle 1 for a total of 2 doses. Participants receive glofitamab IV on days 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Participants receive pirtobrutinib PO once a day (QD) on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity up to Cycle 30, Day 22. Participants also undergo FDG-PET/CT at screening, after every 4 cycles through cycle 13 and then after every 6 cycles. Participants will undergo a bone marrow biopsy and aspiration at cycle 13 and blood sample collection throughout study and a tissue biopsy at relapse or progression.

Biological: Obinutuzumab; Biological: Glofitamab; Drug: Pirtobrutinib; Procedure: Tumor Imaging; Procedure: Biospecimen Collection; Device: ClonoSeq Assay; Procedure: Bone Marrow Biopsy

Interventions

Obinutuzumab BIOLOGICAL

Given intravenously (IV)

Also known as: Anti-CD20 Monoclonal Antibody R715, huMAB(CD20), RO5072759

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

Glofitamab BIOLOGICAL

Given IV

Also known as: Anti-CD3 Bispecific Monoclonal Antibody RO7082859, RO7082859

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

Pirtobrutinib DRUG

Given Orally (PO)

Also known as: LOXO-305

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

Tumor Imaging PROCEDURE

Undergo regular care imaging/scans

Also known as: FDG-PET, Computed Tomography (CT)

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

Biospecimen Collection PROCEDURE

Blood and tissue samples

Also known as: Biological Sample Collection

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

ClonoSeq Assay DEVICE

ClonoSEQ is an FDA-cleared, Clinical Laboratory Improvement Amendments of 1988 (CLIA)-validated measure used to determine minimal residual disease (MRD). This helps uncover how much, if any, cancer remains in your body during and after treatment.

Also known as: ClonoSeq

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration.

Also known as: Biopsy of Bone Marrow

Treatment (obinutuzumab, glofitamab, pirtobrutinib)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at the time of signing the informed consent form.
• Have a life expectancy (in the opinion of the investigator) of at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 60%).
• History of previously treated MCL meeting the following criteria: Relapsed after or failed to respond to at least one prior line of systemic therapy including anti-CD20 monoclonal antibody and alkylator-containing chemotherapy.
• At least one bi-dimensionally measurable nodal lesion ( \> 1.5 cm in its largest dimension by PET/CT scan), or at least one bi-dimensionally measurable extranodal lesion ( \> 1.0 cm in its largest dimension by PET/CT scan) and FDG-avid.
• Availability of leftover tissue from the time of progression for pathology confirmation and correlative studies. Note: Formalin fixed paraffin embedded blocks are preferred. If blocks are not available, 12-15 slides containing unstained, serial sections are acceptable.
• Hemoglobin ≥ 9 g/dL (Independent of transfusions and within 7 days prior to screening assessment).
• Absolute neutrophil count \>= 1.0 x 10\^9/L (Independent of growth factor support and within 7 days prior to screening assessment).
• Platelets ≥ 75 x 10\^9/L or \>= 50 x 10\^9/L if due to bone marrow involvement (Independent of transfusions and within 7 days prior to screening assessment, and independent of growth factor support and within 7 days prior to screening assessment). If the patient is cytopenic there should be no evidence of myelodysplasia orhypoplastic bone marrow.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (or ≤ 3 x ULN for participants with Gilbert syndrome, or \<= 3 x ULN if due to underlying lymphoma).
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT)) \<= 2.5 X institutional upper limit of normal.
• Alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase (SGPT)) \<= 2.5 X institutional upper limit of normal.
• Creatinine clearance \>= 50 mL/min (by Cockcroft-Gault formula).
• Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) \<= 1.5 x ULN.
• Prothrombin (PT) or (international normalized ratio (INR) \<= 1.5 x ULN.

You may not qualify if:

• Pregnant, or intention of becoming pregnant during the study or within 18 months after treatment with obinutuzumab or 2 months after the last dose of glofitamab, or 3 months after treatment with tocilizumab, whichever is longer; and 1 month after the last dose of pirtobrutinib.
• Participants should avoid chest-feeding until at least 1 week after discontinuing pirtobrutinib.
• Have received the following treatments/procedures prior to study entry:
• Participants who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor. NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome)
• Participants who discontinued a covalent BTK inhibitor due to disease progression or relapse. NOTE: Participants who discontinued covalent BTK inhibitor therapy due to intolerance will not be excluded. Covalent BTK inhibitor intolerance is defined as:
• Any grade 1 or higher non-hematologic toxicity that lasted longer than 7 days or recurred
• Any grade 4 hematologic toxicity
• Neutropenic fever
• Discontinuation due to drug interaction/expected toxicity with resolution of prior covalent BTK inhibitor-related toxicities
• Any CD20/CD3-directed bispecific antibodies for treatment of lymphoma
• Allogeneic stem cell transplant (SCT) within 6 months or on active immunosuppression or active graft versus host disease (GVHD)
• Solid organ transplantation
• Have received the following treatments/procedures prior to study entry whether investigational or approved, within the respective time periods prior to initiation of study treatment:
• Radiotherapy within 2 weeks prior to the first dose of study treatment. Note: If participants have received radiotherapy within 4 weeks prior to the first study treatment administration, participants must have at least one measurable lesion outside of the radiation field
• Autologous SCT within 90 days prior to first study treatment

Sponsors & Collaborators

• University of California, San Francisco: lead
• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator
• Adaptive Biotechnologies: collaborator

Study Sites (3)

University of California, Davis

Davis, California, 95616, United States

RECRUITING

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

obinutuzumab; glofitamab; pirtobrutinib

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

Study Officials

• Madhav Seshadri, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF Hematopoietic Malignancies Clinical Trial Recruitment

CONTACT

877-827-3222; HDFCCC.Heme@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 12, 2024
• Study Start: June 11, 2024
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)