On July 20, 2022 ADC Therapeutics SA (NYSE: ADCT) reported the first patient has been dosed in LOTIS-9, a Phase 2 clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) in combination with rituximab (Lonca-R) in unfit and frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, ADC Therapeutics, JUL 20, 2022, View Source [SID1234616790]).

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The initial exploratory stage of the LOTIS-9 open-label Phase 2 trial is evaluating the efficacy and tolerability of Lonca-R in approximately 80 unfit or frail patients aged 80 years or older with previously untreated DLBCL. The simplified geriatric assessment (sGA) developed by the Fondazione Italiana Linfomi identifies three distinct categories (fit, unfit, and frail) based on age, activities of daily living, instrumental activities of daily living and the Cumulative Illness Rating Scale for Geriatrics. Trial participants will be assigned to either Cohort A (unfit) or Cohort B (frail) using the sGA. For more information about the LOTIS-9 trial, please visit www.clinicaltrials.gov (identifier NCT05144009).

About LOTIS-9

The LOTIS-9 Phase 2 clinical trial is evaluating loncastuximab tesirine-lpyl in combination with rituximab (Lonca-R) in previously untreated unfit/frail participants with DLBCL. The primary objectives of the Phase 2 clinical trial are to assess the efficacy of a response-adapted treatment of Lonca-R in unfit participants with previously untreated DLBCL and to assess the tolerability and efficacy of a response-adapted treatment of Lonca-R in frail participants with previously untreated DLBCL who are ineligible for standard R-mini-CHOP.

The first arm of this study will examine participants who are unfit and who will receive Lonca-R for three cycles. Participants who achieve a complete response will receive Lonca-R for one additional cycle. Participants who receive a partial response will receive Lonca-R for three additional cycles. The second arm of this study will examine participants who are frail or participants with cardiac comorbidities. These participants will receive Lonca-R for three cycles. Participants who achieve a PR will receive Lonca-R for 3 additional cycles for a total of up to 6 cycles. Only participants enrolled in Cohort B, who achieve stable disease (SD) and deriving clinical benefit per the treating physician, may also receive Lonca-R for an additional 3 cycles.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.