Use of LOncastuximab Tesirine in patients with RElapsed/Refractory Diffuse Large B-Cell LYmphoma (DLBCL) or High Grade B-Cell Lymphoma (HGBCL) who have progressive disease after CAR T-cell treatment - LORELY

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Humanitas Mirasole S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

19 Jun 2023 → ongoing

Decision date (initial)

2024-10-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516929-31-00

EudraCT number

2022-001147-24

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Assess the efficacy of loncastuximab tesirine as measured by overall response rate (ORR) in DLBCL and HGBCL patients failing CAR-T cell therapy

Secondary objectives 2

1. • Evaluate survival outcomes after Loncastuximab Tesirine • Evaluate the safety of loncastuximab tesirine
2. Exploratory Objectives • Assess the changes in blood serum markers of disease and inflammation during the study course • Explore the correlation between clinical activity and changes in plasma circulating tumor DNA (ctDNA) during the study course

Conditions and MedDRA coding

Patients affected by relapsed/refractory DLBCL or HGBCL failing CAR T-cell therapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Male or female, aged ≥18 years. 2. Willing and able to give written, informed consent. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 4. Histologically confirmed DLBCL or large B cell lymphoma (at last relapse) as defined by the 2016 WHO classification, including one of the following: • DLBCL, Not Otherwise Specified (NOS) • Transformed DLBCL from indolent lymphoma • HGBCL with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit) 5. Patients failing CAR T-cell therapy, defined as: a. Progressive disease (PD) at any time b. Partial Remission (PR) or stable disease (SD) at 3 months after CAR T-cell infusion. 6. Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or MRI if tumour is not FDG-avid on screening PET-CT. 7. Previous treatment with loncastuximab tesirine is allowed, provided that the patient was in CR or PR at the time of drug withdrawal. 8. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential. 9. Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the patient receives his last dose of loncastuximab tesirine. 10. Adequate renal, hepatic, pulmonary, and cardiac function defined as: • Creatinine clearance ≥40 ml/min. • Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x ULN. • Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome. • Known history of LVEF ≥50% unless the institutional lower limit of normal is lower. • Baseline oxygen saturation >92% on room air and ≤Grade 1 dyspnoea. 11. Adequate Bone Marrow (BM) function without requiring ongoing blood product or granulocyte-colony stimulating factor support (GCSF) and meeting the following criteria: • Absolute neutrophil count ≥1.0 × 10^6/dL. • Haemoglobin ≥9.0 g/dL • Platelets ≥50 × 10^6/dL

Exclusion criteria 1

1. 1. Known history of hypersensitivity to or positive serum human antidrug antibody (ADA) to a CD19 antibody. 2. Females who are pregnant or lactating.3. Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary. 4. Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease. 5. Bulky disease, defined as largest tumour diameter >10 cm. 6. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). 7. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath) 8. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure ≥160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease. 9. Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other central nervous system (CNS) autoimmune disease. 10. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome. 11. Major surgery, radiotherapy, chemotherapy or other antineoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. 12. Planned live vaccine administration after starting study drug (C1D1). 13. Use of any other experimental medication within 14 days prior to start of study drug (C1D1). 14. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events version 5.0 [CTCAE v5.0]) from acute nonhematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening. 15. Any other significant medical illness, abnormality, or condition that would, in the Investigator’s judgment, make the patient inappropriate for study participation or put the patient at risk.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR) defined as patients in achieving a best overall response of complete response (CR) or partial response (PR) to study treatment, according to the 2014 Lugano Classification

Secondary endpoints 3

1. • Progression-free survival (PFS) defined as the time between first dose administration and the first documentation of recurrence or progression by independent central review, or death • Overall survival (OS) defined as the time between first dose administration and death from any cause • Duration of Response (DOR) defined as the time from first documentation of response to recurrence or progression by independent central review, or death
2. • Frequency and severity of adverse events (AEs) and severeserious adverse events (SAEs)
3. Exploratory • Relationship between blood serum markers of disease and inflammation (LDH, CRP, ferritin) and selected efficacy endpoints • Relationship between changes in plasma ctDNA and selected efficacy endpoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Humanitas Mirasole S.p.A.

Sponsor organisation

Humanitas Mirasole S.p.A.

Address

Via Alessandro Manzoni 56

City

Rozzano

Postcode

20089

Country

Italy

Scientific contact point

Organisation

Humanitas Mirasole S.p.A.

Contact name

Michele Lagioia

Public contact point

Organisation

Humanitas Mirasole S.p.A.

Contact name

Michele Lagioia

Third parties 1

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications