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)
Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
ADCT-402-105 (primary)
NCI-2022-04828
2021-001071-16
Summary
The primary objective of this study is to characterize the safety and tolerability of
loncastuximab tesirine in combination with polatuzumab vedotin, glofitamab, or
mosunetuzumab, and to identify the maximum tolerated dose (MTD) and/or recommended dose
for expansion (RDE) for the combinations.
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.
Eligibility
- Male or female participant aged 18 years or older
- Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) B-NHL (2016 World Health Organization classification) who have failed, or been intolerant to any approved therapy and had received at least two systemic treatment regimens in dose-escalation part; and at least one systemic treatment regimen in dose-expansion part
- DLBCL (including transformed diseases, but for Arms E and F, including transformed FL only)
- HGBCL
- FL
- MZL
- MCL (for Arm C only)
- BL (for Arm C only)
- Life expectancy of at least 24 weeks according to Investigator's judgement
- Need of systemic treatment for any of the listed indications as assessed by the investigator, including indolent B-NHLs (e.g. FL and MZL)
- Measurable disease as defined by the 2014 Lugano Classification
- Availability of formalin-fixed paraffin-embedded tumor tissue block
- ECOG performance status 0 to 2
- Adequate organ function
- Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent the first dose until at least 7 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period. For the arm that includes glofitamab, WOCBP must agree to use contraceptive methods that result in a failure of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 18 months after pretreatment with obinutuzumab. For the arm that includes mosunetuzumab, WOCBP must agree to use contraceptive methods that result in a failure of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable).
Treatment Sites in Georgia
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