Open-label of Loncastuximab Tesirine (ADCT-402) in Relapsed/Refractory Marginal Zone Lymphoma

NCT05296070 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20211204
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this research study is to see if loncastuximab tesirine has any benefits at dose levels researchers found acceptable in earlier studies in patients with related forms of immune cell cancers. The researchers want to find out the effects (good and bad) that loncastuximab tesirine has on the participant and the participant's condition.

Conditions

Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR) rate of Loncastuximab tesirine in relapsed/refractory at 6 months

  CR rate is defined as the Complete Response (CR)/n, where n is the number of participants. The proportion of patients with best overall response of complete response (CR), per Cheson criteria if disease is not PET (Positron emission tomography)-avid in initial screening and by revised Lugano criteria if screening PET-CT demonstrated PET-avid disease.CR will be defined by a Deauville score of ≤ 3.

  6 months.

• Complete Response (CR) rate of Loncastuximab tesirine in relapsed/refractory at 12 months

  CR rate is defined as the Complete Response (CR)/n, where n is the number of participants. The proportion of patients with best overall response of complete response (CR), per Cheson criteria if disease is not PET-avid in initial screening and by revised Lugano criteria if screening PET-CT demonstrated PET-avid disease.CR will be defined by a Deauville score of ≤ 3.

  12 months.

Secondary Outcomes (8)

• Partial Response rate at 6 months

  6 months

• Partial Response rate at 12 months

  12 months

• Overall response rate (ORR) at 6 months

  6 months

• Overall response rate (ORR) at 12 months

  12 months

• Progression-free survival (PFS)

  2 years

Study Arms (1)

Loncastuximab tesirine Cycles 1-6

EXPERIMENTAL

Patients will be treated with loncastuximab tesirine for a total of 6 cycles on Day 1 (+/-3) of each 21 day (3 week) cycle. The total duration of treatment is approximately 18 weeks (4.5 months)

Drug: Loncastuximab tesirine 150 µg/Kg; Drug: Loncastuximab tesirine 75µg/Kg

Interventions

Loncastuximab tesirine 150 µg/Kg DRUG

Participants will be treated with loncastuximab tesirine at a dose of 150 µg/Kg given as an intravenous infusion (given as per treatment guidelines for 30 minutes or longer) on Day 1 (+/- 3 days) of each 21 day cycle for Cycle 1 - 2.

Loncastuximab tesirine Cycles 1-6

Loncastuximab tesirine 75µg/Kg DRUG

Participants will be treated with loncastuximab tesirine at a dose of 75 µg/Kg given as an intravenous infusion (given as per treatment guidelines for 30 minutes or longer) on Day 1 (+/- 3 days) of each 21 day cycle for Cycle 3 - 6.

Loncastuximab tesirine Cycles 1-6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, aged 18 years or older.
• Histologically confirmed MZL, including extranodal, nodal, and splenic subtypes.
• Previously received 1 or more lines of systemic therapy, including at least 1 anti-CD20 antibody (cluster of differentiation antigen 20) (either as monotherapy or in combination as chemoimmunotherapy), with documented progression or documented failure to achieve CR or PR after the most recent systemic treatment regimen. Subjects with H. pylori-positive gastric extranodal MZL who received an initial treatment with currently accepted antibiotics may be considered eligible if, after antibiotic regimen, subject has histologically confirmed MZL and was subsequently treated with at least 1 line of systemic therapy.
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures \> 1.5 cm in the LDi and ≥ 1.0 cm in the longest perpendicular diameter as assessed by CT or MRI per response criteria for lymphomas.68 Imaging must be conducted within 6 weeks prior to the start of therapy.
• Subjects with splenic MZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that bone marrow infiltration of MZL is histologically confirmed.
• Subjects with skin EMZL (extranodal marginal zone lymphoma) who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that skin lesion measures ≥ 1.5 cm in diameter by tape measure and is documented by photo or there are multiple skin lesions measuring \>1cm in diameter on the body that cannot be incorporated in one radiation field and at least one of them is histologically confirmed as MZL.
• Subjects with gastric extranodal MZL histologically confirmed and need therapy but do not have measurable disease and in which response to treatment can be assess by multiple random gastric biopsies.
• Subjects with conjunctival EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that conjunctival lesion measures ≥ 1 cm in diameter by tape measure and is documented by photo or there are multiple conjunctival lesions measuring together \>1 5cm that cannot be treated by radiation because of previous radiation therapy, contraindications to radiation and patient refusal to receive radiation therapy. At least one of these lesions needs be histologically confirmed as MZL.
• Subjects must be willing to provide a lymph node or tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy.
• a. Subjects with splenic MZL who do not have a tumor to biopsy or an archival tumor tissue sample are eligible for participation provided subject is willing to undergo a bone marrow biopsy or provide an archival bone marrow biopsy that was obtained before the date of the first dose of study treatment; bone marrow sample must show histologically confirmed infiltration of MZL.
• Patient should have at least one of the following criteria for treatment initiation):
• Involvement of ≥3 nodal sites, each with diameter of ≥3 cm
• Any nodal or extranodal tumor mass with a diameter of ≥5 cm
• B symptoms (fever ≥ 38 degrees Celsius of unclear etiology, night sweats, weight loss \> 10% within the prior 6 months) or other symptoms attributed to disease or specific organ involvement associated with the relapse.
• Risk of local compressive symptoms that may result in organ compromise

You may not qualify if:

• Evidence of DLBCL transformation. a. Subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase, rapidly worsening disease, or frequent B-symptoms, must be ruled out for a transformation to a more aggressive disease, such as DLBCL.
• History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease.
• Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
• Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment.
• Active graft versus host disease.
• Receipt of anticancer medications or investigational drugs within the following intervals before the date of the first dose of study treatment:
• \< 10 weeks from completion of any radio- or toxin-immunoconjugates.
• \< 4 weeks for immunotherapy
• \<. 3 weeks for radiotherapy.
• \< 2 weeks for any investigational agent or other anticancer medications.
• Steroids that are used for treatment of allergy or other underlying condition are permittable, but not steroids started to treat lymphoma. Subjects receiving corticosteroids must be at a dose level ≤ 10 mg/day within 7 days of the study treatment administration.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
• Prior treatment-related toxicities have not resolved to NCI CTCAE v5.071 ≤ Grade 1 before the date of the first dose of study treatment, except for stable chronic toxicities (≤ Grade 2) not expected to resolve (eg, stable Grade 2 peripheral neurotoxicity).
• Previous treatment with anti CD19 (cluster of differentiation antigen 19 ) approaches
• Current or previous other malignancy within 3 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy.

Sponsors & Collaborators

• University of Miami: lead
• ADC Therapeutics S.A.: collaborator

Study Sites (4)

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

loncastuximab tesirine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Izidore Lossos, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philip Arlen, PhD

CONTACT

3052435247; paa107@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: March 25, 2022
• Study Start: June 21, 2022
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)