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

Conditions: Non-Hodgkins Lymphoma

Summary: 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 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