a study of cln-978 in patients with relapsed or refractory (r/r) b cell non-hodgkin lymphoma (b-nhl)

Conditions: NHL; NHL, Relapsed, Adult

Summary: cln-978-001 is a phase 1, open-label, dose escalation and dose expansion study of cln-978 in patients with relapse/refractory (r/r) b-cell non-hodgkin lymphoma (b-nhl).


Eligibility criteria:
inclusion criteria: * eastern cooperative oncology group (ecog) ps ≤ 2 * documented diagnosis of one of the below cd19+ b-cell neoplasms according to who classification (swerdlow et al., 2016) or who classification 2008: 1. diffuse large b-cell lymphoma - de novo or transformed 2. high-grade b-cell lymphoma 3. primary mediastinal large b-cell lymphoma 4. follicular lymphoma 5. mantle cell lymphoma 6. marginal zone lymphoma (nodal, extranodal, or mucosa-associated) * relapsed, progressive, and/or refractory disease after at least 2 lines of therapy. * for part b expansion cohorts: 1. cohort b1: r/r dlbcl that has relapsed after at least 2 prior therapies including a cd20 monoclonal antibody and anthracycline. 2. cohort b2: r/r fl (grade 1-3a) that has relapsed after at least 2 prior therapies including cd20 monoclonal antibody and an alkylating agent. 3. cohort b3: other r/r b-nhl. * measurable disease defined as ≥1 measurable nodal lesion (long axis \>1.5 cm and short axis \>1.0 cm) or ≥1 measurable extra-nodal lesion (long axis \>1.0 cm) on computed tomography (ct) scan or magnetic resonance imaging (mri) and baseline fluorodeoxyglucose-positron emission tomography (fdg-pet) scan demonstrating positive lesion(s) compatible with ct- or mri-defined anatomical tumor sites. * laboratory parameters including the following: 1. lymphocyte count \< 5 x 10\^9/l 2. platelet count ≥ 75 x 10\^9/l 3. absolute neutrophil count ≥ 1.0 x 10\^9/l; growth factor support allowed in cases of documented bone marrow involvement 4. hemoglobin ≥ 9 g/dl, with or without transfusion 5. creatinine clearance ≥ 45 ml/min 6. total bilirubin ≤ 1.5 × upper limit of normal (uln), except patients with confirmed gilbert's syndrome 7. aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 3.0 × uln (unless attributed to hepatic involvement by lymphoma) exclusion criteria: * primary cns lymphoma or known cns involvement by lymphoma at study screening * known past or current malignancy other than the inclusion diagnosis * known clinically significant cardiac disease * significant central nervous system disease * prior organ allograft * confirmed history or current autoimmune disorder or other disease requiring ongoing immune suppression * active hepatitis c virus (hcv), hepatitis b virus (hbv), or known human immunodeficiency virus (hiv) infection * live virus vaccines within 28 days of the first dose of cln-978, during treatment, and until the end of last dose of cln-978 * known active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection, including coronavirus disease of 2019 (covid-19) infection, at the time of enrollment or within 7 days of the first dose of cln-978. * prior treatment with any of the following: 1. allogeneic hsct 2. autologous hsct within 30 days prior to the first dose of cln-978 3. chimeric antigen receptor t cell therapy (car-t) within 30 days prior to the first dose of cln-978 4. any investigational cd19 x cd3 t cell engager (tce) 5. unconjugated cd19 monoclonal antibody ≤ 4 weeks prior to the first dose cln-978 6. radio-conjugated or cd19 antibody-drug conjugate ≤ 12 weeks prior to the first dose cln-978 7. investigational or standard of care monoclonal antibodies, chemotherapy, or other investigational agent ≤ 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of cln-978 8. radiation therapy (xrt), with the exception of focal treatment for symptom control, ≤ 4 weeks of the first dose of cln-978 * woman of child-bearing potential who is pregnant, breast-feeding, or plans to become pregnant * male patients who plan to father a child or donate sperm within 120 days of last study drug administration

Keywords: relapsed/refractory b-cell non-hodgkin lymphoma