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

ConditionsChronic Lymphocytic LeukemiaRichter's Transformation
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorChristine Ryan

About this trial

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)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per IW-CLL 2018 criteria with biopsy proven transformation to diffuse large B-cell lymphoma (DLBCL), consistent with Richter's Transformation. The diagnostic sample must be reviewed by the treating institution. Tumor sample may be obtained by core needle or excisional surgical biopsy. A fresh biopsy is encouraged, but an archival sample is acceptable if the following provisions are met: 1) availability of a tumor-containing formalin-fixed, paraffin-embedded (FFPE) tissue block, 2) if the tumor containing FFPE tissue block cannot be provided in total, sections from this block should be provided. Biopsy can be obtained up to 3 months prior to first day of treatment.

Glofitamab monotherapy cohort: Patients with either relapsed/refractory or previously untreated Richter's Transformation.

Glofitamab + polatuzumab vedotin cohort: Patients with previously untreated RT. After the first 10 patients are enrolled in this cohort irrespective of prior BTKi exposure status, the remainder of the patients enrolled to this cohort must have previously untreated RT and no prior BTK inhibitor. Patients cannot have prior polatuzumab vedotin exposure.

Glofitamab + pirtobrutinib cohort: Patients with previously untreated RT and prior BTK inhibitor exposure (with enrollment to begin only after the first 10 patients are accrued to the polatuzumab combination cohort). Patients cannot have prior pirtobrutinib exposure.

Disqualifiers

Patients with the Hodgkin variant transformation of CLL will be excluded.

No prior anti-CD20 bispecific antibody is allowed. No prior, polatuzumab vedotin is allowed for patients in the polatuzumab vedotin-containing combination arm. No prior, or atezolizumab therapy is allowed for patients in the atezolizumab-containing combination arm. No prior pirtobrutinib is allowed for patients in the pirtobrutinib-containing arm.

Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of treatment: investigational agents, targeted therapies, e.g. tyrosine kinase inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not limited to, CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, radio-immunoconjugates, antibody-drug conjugates (patients in the pirtobrutinib combination arm may not have received an antibody-drug conjugate within 28 days prior to the first dose of study treatment), immune/cytokines and monoclonal antibodies. Patients who are currently receiving treatment with a Bruton's tyrosine kinase inhibitor may continue this agent until the day prior to starting treatment, to reduce the risk of tumor flare on treatment cessation.

Prior treatment with CAR T-cell therapy within 30 days before first study treatment administration.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Glofitamab

    Drug

    "2:1" T-cell bispecific humanized monoclonal antibody, administered via intravenous infusion per protocol.

  • Obinutuzumab

    Drug

    Humanized glycoengineered type II anti-CD20 monoclonal antibody, administered via intravenous infusion per protocol.

  • Polatuzumab Vedotin

    Drug

    Antibody-drug conjugate, administered via intravenous infusion per protocol.

  • Atezolizumab

    Drug

    Humanized immunoglobulin monoclonal antibody, administered via intravenous infusion per protocol.

  • Tocilizumab

    Drug

    For the treatment of Cytokine Release Syndrome. Recombinant, humanized, anti-human monoclonal antibody, administered via intravenous infusion per protocol.

  • Pirtobrutinib

    Drug

    Selective inhibitor of BTK, 50 mg or 100 mg tablet, via oral administration per protocol.

Treatment groups

70 Participants
are divided into 4 treatment groups
Group A: Monotherapy Cohort: Obinutuzumab and GlofitamabActive comparator 3 interventions
Group B: Combination A Group: Obinutuzumab, Glofitamab, and Polatuzumab VedotinExperimental treatment 4 interventions
Group C: Combination B Group: Obinutuzumab, Glofitamab, and PirtobrutinibExperimental treatment 4 interventions
Group D: Combination C Group: Obinutuzumab, Glofitamab, and AtezolizumabExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Best Complete Response (CR) Rate

Best Complete Response (CR) rate is defined as the proportion of participants achieving CR at any of the 3 timepoints (after 4, 8 and 12 cycles). CR is defined per Lugano 2014 criteria.

Time frame
Disease evaluation will be performed at 12, 24 and 36 weeks

Secondary outcomes

1

Best Overall Response Rate (ORR)

Best Overall response rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) at any of the 3 timepoints (after 4, 8 and 12 cycles). CR and PR are defined per Lugano 2014 criteria.

Time frame
Disease evaluation will be performed at 12, 24 and 36 weeks
2

Best Partial Response (PR) Rate

Best Partial response (PR) rate is defined as the proportion of participants achieving partial response at any of the 3 timepoints (after 4, 8, 12 cycles). PR is defined per Lugano 2014 criteria.

Time frame
Disease evaluation will be performed at 12, 24 and 36 weeks
3

Overall Response Rate at 36 weeks

Overall response rate (ORR) at 36 weeks is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) at the time of disease evaluation at 12 cycles (36 weeks). CR and PR are defined per Lugano 2014 criteria.

Time frame
36 weeks
4

Partial Response (PR) Rate at 36 weeks

Partial Response (PR) rate at 36 weeks is defined as the proportion of participants achieving PR at the time of disease evaluation at 12 cycles (36 weeks). PR defined per Lugano 2014 criteria.

Time frame
36 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Christine Ryan

Lead sponsor

Dana-Farber Cancer Institute

Sponsor institution

Genentech, Inc.

Collaborator

Loxo Oncology, Inc.

Collaborator

Eli Lilly and Company

Collaborator

Source ClinicalTrials.gov
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