An Open-Label, Multi-Center, Phase IB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin (Plus a Single Pre-Treatment Dose of Obinutuzumab) in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Study Identifier:
NP39488
CT.gov Identifier:
NCT03533283
EudraCT Identifier:
2017-004835-36
EU Trial (CTIS) Number:
2023-505222-34-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

To assess the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for this combination treatment

To evaluate the general safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and preliminary anti-tumor activity of this combination treatment in adult patients.

to present updated study results

To present updated results with longer follow-up in a greater number of pts with R/R LBCL, including pts with HGBCL and prior chimeric antigen receptor (CAR) T-cell therapy, at the previously confirmed recommended Phase II dose of Glofit (30mg, from Part I of the study) when combined with Pola

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Lymphoma
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Arms:
    • Read More
  • Drug: Drug: Atezolizumab
  • Drug: Drug: Obinutuzumab
  • Drug: Experimental: Polatuzumab Vedotin
  • Drug: Drug: Tocilizumab
  • Drug: All patients will receive study treatment every 3 weeks (a cycle) for 8 cycles, unless they discontinue early. Patients who achieve a partial response/stable disease will receive 9 additional cycles of treatment. Following the last dose of treatment, all patients will enter into long-term follow-up.
  • Drug: ASH 2019:
  • Drug: Experimental: Imaging Sub-study
  • Drug: Drug: 89Zr-Df-IAB22M2C
  • Drug: This study includes an additional open-label imaging feasibility sub-study using a tracer in adult participants with relpased/refractory B-cell non-Hodgkin's lymphoma to image CD8+T-cells at baseline and after treatment with glofitamab, including pre-treatment with obinutuzumab.
  • Drug: ASH 2021
  • Drug: ICML 2023
  • Drug: Patients received obinutuzumab 1000mg on Cycle (C) 1 Day (D) 1 to mitigate the risk of severe cytokine release syndrome (CRS). Pola 1.8mg/kg was given on C1D2 and D1 of C2-6 (21-day cycles). Glofit was given with step-up dosing in C1 (C1D8 2.5mg; C1D15 10mg; D1 of C2-12 10/30mg) for up to 12 cycles.
  • Drug: ASH 2024:
  • Drug: Pubmed
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Histologically-confirmed hematologic malignancy that is expected to express CD20 (Relapsed after or refractory to respond to at least one prior treatment regimen; no available treatment options that are expected to prolong survival or patients refusing chemotherapy or autologous stem cell transplant (SCT))
    • Dose-escalation: Grades 1-3b relapsed or refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL) (nodal; extra-nodal; or splenic), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements (double-hit lymphoma), HGBCL not otherwise specified (NOS), DLBCL arising from FL (transformed FL)
    • Dose-expansion: R/R LBCL, including DLBCL NOS, DLBCL arising from FL (transformed FL), PMBCL, HGBCL with MYC and BCL2 and/or BCL6 rearrangements (i.e., double-hit and triple-hit lymphomas), and HGBCL NOS
    • At least one measurable target lesion
    • Fresh pre-treatment biopsy, but if this cannot be taken, a previous archived biopsy from metastatic lesion can be taken as replacement if it is not older than 6 months and not confounded by major events (progression, treatment)
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
    • Adequate organ function (liver, hematological, renal)
    • Negative test results for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV)
    • Inclusion Criteria Specific to Imaging Substudy
    • At least two measurable target lesions
    • Able to provide two fresh tumor biopsies (baseline and on-treatment)
    Exclusion criteria
    • Main Exclusion Criteria
    • Participants with Chronic Lymphocytic Leukemia (CLL), acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, Richter's transformation, CD20-positive ALL, Burkitt lymphoma, or lymphoplasmacytic lymphoma
    • Current > Grade 1 peripheral neuropathy (only for participants being treated in the polatuzumab vedotin arm)
    • Patients with known active infection, or reactivation of a latent infection within 4 weeks prior to Obinutuzumab (Gpt) infusion
    • Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
    • History of leptomeningeal disease
    • Current or past history of central nervous system (CNS) lymphoma
    • Current or past history of CNS disease
    • Major surgery or significant traumatic injury
    • Significant cardiovascular disease or significant pulmonary disease
    • Active or history of autoimmune disease or immune deficiency (with exceptions, e.g. hypothyroidism and Diabetes mellitus Type 1)
    • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
    • Treatment with any other standard anti-cancer radiotherapy / chemotherapy including investigational therapy within 4 weeks prior to Gpt infusion
    • Prior solid organ transplantation
    • Prior allogenic stem cell transplant (SCT)
    • Autologous SCT within 100 days prior to Gpt infusion
    • Documented refractoriness to an obinutuzumab-monotherapy regimen
    • Prior treatment with anti-cancer/lymphoma therapies and systemic immunotherapeutic/immunostimulating agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to Gpt infusion
    • Any history of immune related >/= Grade 3 adverse events (AE) with the exception of endocrinopathy managed with replacement therapy
    • Ongoing corticosteroid use >25 milligrams/day of prednisone or equivalent within 4 weeks prior to and during study treatment
    • Treatment with systemic immunosuppressive medication
    • Administration of a live, attenuated vaccine within 4 weeks prior to Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment
    • Exclusion Criteria Specific to Imaging Substudy
    • Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count and/or the presence of abnormal/malignant cells in the peripheral blood differential signifying circulating lymphoma cell
    • Participants who have had splenectomy or functional asplenia that could compromise protocol objectives

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Daniel Morillo Giles
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Lymphoma