A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)

Summary

Objectives

This is a Phase 1b, multi-center, open-label, multi-arm study to evaluate the safety and
anti-cancer activity of loncastuximab tesirine in combination with polatuzumab vedotin,
glofitamab, or mosunetuzumab in participants with relapsed or refractory B-cell
Non-Hodgkin Lymphoma (R/R B-NHL). The study will enroll approximately 200 participants.

Loncastuximab tesirine (ADCT-402; Zynlonta) is an antibody drug conjugate (ADC), composed
of a humanized monoclonal antibody directed against human cluster of differentiation 19
(CD19) conjugated through a cathepsin-cleavable linker to a pyrrolobenzodiazepine (PBD)
dimer cytotoxin. Loncastuximab tesirine has been granted by Food and Drug Administration
(FDA) as accelerated approval for adult participants with relapsed or refractory large
B-cell lymphoma after two or more lines of systemic therapy, including diffuse large
B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma,
and high-grade B-cell lymphoma (HGBCL). In the European Union (EU), the European
Commission (EC) granted conditional approval for the treatment of adult patients with
relapsed or refractory DLBCL and HGBCL, after two or more lines of systemic therapy.

The study includes multiple arms in two parts, Dose Escalation part (Part 1) and Dose
Expansion part (Part 2). In Part 1, for the arm of loncastuximab tesirine in combination
with polatuzumab vedotin includes DLBCL, HGBCL, follicular lymphoma (FL), mantle cell
lymphoma (MCL), marginal zone lymphoma (MZL), and Burkitt lymphoma (BL); for the arms of
loncastuximab tesirine in combination with glofitamab or mosunetuzumab include DLBCL,
HGBCL, FL, and MZL. In Part 2, participants will be treated at the dose level determined
from Part 1. The Sponsor will conduct the safety monitoring and the overall supervision
of the study in consultation with the Dose-Escalation Steering Committee (DESC).

For each participant, the study will include a Screening Period (of up to 28 days), a
Treatment Period (cycles of 21 days), and a Follow-up Period (approximately every 12 week
visits for up to two years). Participants may continue treatment for up to one year or
until disease progression, unacceptable toxicity, or other discontinuation criteria,
whichever occurs first.

Treatment with gemcitabine (Arm A), lenalidomide (Arm B), and umbralisib (Arm D) were
removed.