NCT06043674

Phase 2 Study of Glofitamab Monotherapy & With Polatuzumab Vedotin, Pirtobrutinib, or Atezolizumab in Richter's Transformation

A Phase 2 Study of Glofitamab as Monotherapy or in Combination With Polatuzumab Vedotin, Pirtobrutinib, or Atezolizumab in Richter's Transformation

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Christine Ryan · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research is being done to evaluate Glofitamab by itself or in combination with Polatuzumab Vedotin, Pirtobrutinib, or Atezolizumab as possible treatments for Chronic Lymphocytic Leukemia (CLL) that has transformed into Richter's Transformation (RT). The names of the study drugs involved in this research study are: * Glofitamab (a T-cell bispecific humanized monoclonal antibody) * Obinutuzumab (a humanized glycoengineered type II anti-CD20 monoclonal antibody) * Polatuzumab vedotin (an antibody-drug conjugate) * Pirtobrutinib (a selective inhibitor of BTK) * Atezolizumab (a humanized immunoglobulin monoclonal antibody) * Tocilizumab (a recombinant, humanized, anti-human monoclonal antibody)

Detailed description

This is an open-label, multicenter phase II study to evaluate the efficacy and safety of glofitamab as monotherapy and in combination with polatuzumab vedotin, pirtobrutinib, or atezolizumab for participants with Richter's Transformation (RT) that has transformed from chronic lymphocytic leukemia (CLL). The U.S. Food and Drug Administration (FDA) has not approved glofitamab, obinutuzumab, polatuzumab vedotin, pirtobrutinib or atezolizumab for RT, but each drug has been approved for other uses. Glofitamab has been approved by the FDA for certain people with diffuse large B-cell lymphoma (DLBCL), which is similar to Richter's Transformation. Glofitamab has been studied as a single therapy and in combination with polatuzumab vedotin and atezolizumab in people with DLBCL. Polatuzumab vedotin is already an approved therapy for diffuse large B-cell lymphoma in combination with chemoimmunotherapy. Pirtobrutinib is an approved therapy for chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma. Atezolizumab is an approved therapy for other cancers. Obinutuzumab is an approved therapy for chronic lymphocytic leukemia. Tocilizumab is approved for the treatment of an entity called cytokine release syndrome following another therapy called chimeric antigen receptor T-cell therapy; it will be used to treat cytokine release syndrome if a participant develops it in this study. Study procedures include screening for eligibility, clinic visits for study treatment, blood and urine tests, Positron Emission Tomography (PET) or Computed Topography (CT) scans, bone marrow biopsies, echocardiograms, and electrocardiograms (ECGs). Participants will receive study treatment for about 9 months and will be followed every 3-6 months for up to 10 years thereafter. It is expected that about 70 people will take part in this research study. Genentech, Inc./Loxo Oncology, Inc./Eli Lilly and Company are funding this research study by providing study drugs.

Conditions

• Chronic Lymphocytic Leukemia
• Richter's Transformation

Interventions

Type	Name	Description
DRUG	Glofitamab	"2:1" T-cell bispecific humanized monoclonal antibody, administered via intravenous infusion per protocol.
DRUG	Obinutuzumab	Humanized glycoengineered type II anti-CD20 monoclonal antibody, administered via intravenous infusion per protocol.
DRUG	Polatuzumab Vedotin	Antibody-drug conjugate, administered via intravenous infusion per protocol.
DRUG	Atezolizumab	Humanized immunoglobulin monoclonal antibody, administered via intravenous infusion per protocol.
DRUG	Tocilizumab	For the treatment of Cytokine Release Syndrome. Recombinant, humanized, anti-human monoclonal antibody, administered via intravenous infusion per protocol.
DRUG	Pirtobrutinib	Selective inhibitor of BTK, 50 mg or 100 mg tablet, via oral administration per protocol.

Timeline

• Start date: 2024-01-22
• Primary completion: 2028-01-15
• Completion: 2033-01-15
• First posted: 2023-09-21
• Last updated: 2026-01-07

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study