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

Roche

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Non-Hodgkins Lymphoma

Treatments: Drug: Polatuzumab Vedotin; Drug: Tocilizumab; Drug: Glofitamab; Drug: 89Zr-Df-IAB22M2C; Drug: Obinutuzumab; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03533283

NP39488

Details and patient eligibility

About

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.

Enrollment: 211 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

211 participants in 3 patient groups

Atezolizumab

Experimental group

Description:

Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD).

Treatment:

Drug: Obinutuzumab

Drug: Atezolizumab

Drug: Glofitamab

Drug: Tocilizumab

Polatuzumab Vedotin

Experimental group

Description:

Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.

Treatment:

Drug: Obinutuzumab

Drug: Glofitamab

Drug: Polatuzumab Vedotin

Drug: Tocilizumab

Imaging Sub-study

Experimental group

Description:

Participants will undergo positive-emission tomography/computed tomography (PET/CT) at screening, followed by an "Imaging Cycle," to replace Cycle 1 of the main study. Eligible participants will have the option roll-over to the atezolizumab arm of the main study from Cycle 2 onwards.

Treatment:

Drug: Obinutuzumab

Drug: 89Zr-Df-IAB22M2C

Drug: Glofitamab