PHASE 1B OPEN‐LABEL STUDY OF LONCASTUXIMAB TESIRINE IN COMBINATION WITH OTHER ANTICANCER AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY B‐CELL NON‐HODGKIN LYMPHOMA (LOTIS‐7)

Abstract

Introduction: Combining agents with different mechanisms of action may enhance treatment (Tx) efficacy in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an FDA-approved, CD19-directed, antibody-drug conjugate indicated for R/R diffuse large B-cell lymphoma (DLBCL), showed significant efficacy and manageable toxicity in a phase 2 trial in pts with R/R DLBCL. In preclinical models, Lonca + polatuzumab vedotin (Pola) showed improved efficacy. CD20 × CD3 T-cell–engaging antibodies and Lonca target different antigens; combining these is expected to increase efficacy. The safety and activity of Lonca combined with other agents in pts with R/R B-NHL will be evaluated in LOTIS-7. Methods: LOTIS-7, a phase 1b, open-label, multicenter, multiarm study (NCT04970901), will enroll ∼200 pts with B-NHL in part 1 (dose escalation, 60 pts) and part 2 (dose expansion, 140 pts). Part 2 may include specific subpopulation(s) of B-NHL informed by part 1. Primary endpoints are frequency and severity of adverse events (AE), serious AE, dose-limiting toxicities, and frequency of AE-related dose modifications. Secondary endpoints are overall response rate; duration of response; complete response rate; progression-free, relapse-free, and overall survival; Lonca concentrations; and antidrug antibody titers. Planned arms include Lonca + Pola (arm C), glofitamab (arm E), or mosunetuzumab (arm F). Arm C enrollment is open: pts are treated with Lonca + Pola as an outpatient infusion. In part 1, arm C pts receive Lonca at escalating doses (90-150 µg/kg) and Pola (1.8 mg/kg) on day 1 of each 3-week cycle; pts in arms E and F will receive Lonca 150 µg/kg for 2 cycles, then 75 µg/kg for subsequent cycles + glofitamab (2.5 mg on cycle [C]1 day [D]8, 10 mg on C1D15, and 10 or 30 mg for C2-12 D1, arm E) or mosunetuzumab subcutaneously (5 mg on C1D1, 15 or 45 mg for C1D8, and 45 mg for C1D15 and C2-8 D1, arm F) after initial step-up dosing. Lonca Tx may continue for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria. Key eligibility criteria include age ≥18 years, pathologic diagnosis of R/R B-NHL (2016 WHO classification), measurable disease (2014 Lugano classification), Tx failure/intolerance, ≥2 lines of prior therapy (LOT) for part 1 (≥1 LOT for part 2), and ECOG performance status of 0-2. Pts previously receiving a study drug could not enroll in that respective study arm. Pts who received a stem-cell transplant within 60 days (100 days for arms E/F) before study Tx; received allogeneic stem cell or solid organ transplant (arms E/F); have lymphoma with active CNS involvement, ascites, edema, or effusion; or have significant comorbidities are excluded. The study opened in December 2021; as of January 2023, 12 pts have been enrolled and 9 treated in the Lonca + Pola arm. Encore Abstract - previously submitted to ASCO 2023 The research was funded by: ADC Therapeutics SA; medical writing: CiTRUS Health Group. Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies, ongoing trials Conflicts of interests pertinent to the abstract. B. T. Hess Consultant or advisory role ADC Therapeutics, Bristol-Myers Squibb/Celgene M. M. Solh Research funding: Partner Therapeutics Other remuneration: Bristol-Myers Squibb, Amgen, AbbVie, Seattle Genetics M. Gandhi Honoraria: GlaxoSmithKline, TG Therapeutics, Karyopharm Therapeutics, Janssen Oncology Y. Wang Employment or leadership position: ADC Therapeutics America, Inc. Stock ownership: Johnson & Johnson (immediate family member) Y. Qin Employment or leadership position: ADC Therapeutics America, Inc. Stock ownership: ADC Therapeutics America, Inc. Research funding: ADC Therapeutics America, Inc. E. Yu Employment or leadership position: ADC Therapeutics America, Inc. Stock ownership: ADC Therapeutics America, Inc., Merck, Zentalis, Karuna Therapeutics, Biomarin P. L. Zinzani Consultant or advisory role Celltrion, Gilead Sciences, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, MSD Oncology, Roche, EUSA Pharma, Kyowa Kirin, Takeda, Secura Bio, TG Therapeutics, Novartis, ADC Therapeutics, Incyte, BeiGene Other remuneration: MSD Oncology, EUSA Pharma, Novartis G. P. Collins Consultant or advisory role Roche, Takeda, Incyte, Pfizer, MSD Oncology, Celgene, BeiGene, Daiichi Sankyo, Celleron Therapeutics, ADC Therapeutics Honoraria: Roche, Takeda, Gilead Sciences, Pfizer, Novartis, Daiichi Sankyo, Incyte, Celleron Therapeutics, MSD Oncology, BeiGene, ADC Therapeutics, AstraZeneca Research funding: MSD Oncology, Celgene, Bristol-Myers Squibb, Amgen, Pfizer Educational grants: Roche, Takeda Other remuneration: Roche, Takeda, Novartis, Gilead Sciences