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An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

NCT03533283

Active Not RecruitingPhase 1, Phase 2

Sponsor: Hoffmann-La Roche

Conditions: Non-Hodgkins Lymphoma

Interventions: Glofitamab, Atezolizumab, Obinutuzumab, Tocilizumab, Polatuzumab Vedotin

Countries: Belgium, Denmark, Israel, Italy, Spain, United Kingdom

This is an open-label, single arm, multicenter, dose finding, Phase Ib study in order to assess the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for this combination treatment and to evaluate the general safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and preliminary anti-tumor activity of this combination treatment in adult patients. 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.

Eligibility overview

Sex: ALL

Age: 18 Years to —

Healthy volunteers: No

Study type: INTERVENTIONAL

Eligibility criteria

Main 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)

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 \</=28 days prior to Gpt infusion
* 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

Locations (19)

Ghent, Belgium
Aarhus N, Denmark
København Ø, Denmark
Odense C, Denmark
Jerusalem, Israel
Petah Tikva, Israel
Ramat Gan, Israel
Naples, Campania, Italy
Bologna, Emilia-Romagna, Italy
Bergamo, Lombardy, Italy
Milan, Lombardy, Italy
Barcelona, Spain
Barcelona, Spain
Madrid, Spain
Málaga, Spain
Valencia, Spain
Leicester, United Kingdom
London, United Kingdom
Newcastle upon Tyne, United Kingdom