Description:
The purpose of this Phase 2 study is to evaluate the clinical efficacy and safety of
Loncastuximab Tesirine (ADCT-402) in patients with relapsed or refractory Diffuse Large
B-Cell Lymphoma.
Title
- Brief Title: Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Official Title: A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Clinical Trial IDs
- ORG STUDY ID:
ADCT-402-201
- SECONDARY ID:
2017-004288-11
- NCT ID:
NCT03589469
Conditions
- Diffuse Large B-Cell Lymphoma Refractory
- Diffuse Large B-cell Lymphoma Recurrent
Interventions
Drug | Synonyms | Arms |
---|
Loncastuximab tesirine | ADCT-402 | Loncastuximab tesirine |
Purpose
The purpose of this Phase 2 study is to evaluate the clinical efficacy and safety of
Loncastuximab Tesirine (ADCT-402) in patients with relapsed or refractory Diffuse Large
B-Cell Lymphoma.
Detailed Description
This is a Phase 2, multi-center, open-label, single-arm study of the efficacy and safety of
loncastuximab tesirine used as monotherapy in patients with relapsed or refractory DLBCL. The
study will enroll approximately 140 patients
Loncastuximab Tesirine is an antibody drug conjugate (ADC) composed of a humanized antibody
directed against human cluster of differentiation 19 (CD19), stochastically conjugated via a
valine-alanine cleavable, maleimide linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin.
Loncastuximab tesirine has been designed to target and kill CD19-expressing malignant
B-cells.
A 2-stage design will be used in this clinical study, with an interim analysis for futility
on the first 52 patients. If ≥10 patients respond (CR+PR), the study will proceed to complete
full enrollment. Enrollment will continue during the interim analysis; however, further
enrollment will be halted if futility is confirmed.
For each patient, the study will include a Screening Period (of up to 28 days), a Treatment
Period (cycles of 3 weeks), and a Follow-up Period (approximately every 12 week visits for up
to 3 years after treatment discontinuation).
Patients may continue treatment until disease progression, unacceptable toxicity, or other
discontinuation criteria, whichever occurs first.
Trial Arms
Name | Type | Description | Interventions |
---|
Loncastuximab tesirine | Experimental | Participants will receive loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg Q3W for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first. | |
Eligibility Criteria
Inclusion Criteria:
- Male or female patient aged 18 years or older.
- Pathologic diagnosis of DLBCL, as defined by the 2016 WHO classification, to include:
DLBCL not otherwise specified; primary mediastinal large B-cell lymphoma; and
high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
- Relapsed or refractory disease following two or more multi-agent systemic treatment
regimens
- Patients who have received previous CD19-directed therapy must have a biopsy that
shows CD19 protein expression after completion of the CD19-directed therapy.
- Measurable disease as defined by the 2014 Lugano Classification
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block or minimum
10 freshly cut unstained slides if block is not available
- ECOG performance status 0-2
- Adequate organ function
- Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior
to start of study drug (C1D1) for women of childbearing potential
- Women of childbearing potential must agree to use a highly effective method of
contraception from the time of giving informed consent until at least 16 weeks 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 16 weeks after
the patient receives his last dose of loncastuximab tesirine.
Exclusion Criteria:
- Previous treatment with loncastuximab tesirine
- Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
- Pathologic diagnosis of Burkitt lymphoma
- 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
- Autologous stem cell transplant (ASCT) within 30 days prior to start of study drug
(C1D1)
- Allogeneic stem cell transplant (AlloSCT) within 60 days prior to start of study drug
(C1D1)
- Active graft-versus-host disease
- Post-transplant lymphoproliferative disorders
- Active autoimmune disease, including motor neuropathy considered of autoimmune origin
and other central nervous system (CNS) autoimmune disease
- Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV)
virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).
- History of Stevens-Johnson syndrome or toxic epidermal necrolysis
- Lymphoma with active CNS involvement at the time of screening, including
leptomeningeal disease
- 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)
- Breastfeeding or pregnant
- Significant medical comorbidities
- Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14
days prior to start of study drug (C1D1), except shorter if approved by the Sponsor
- Use of any other experimental medication within 14 days prior to start of study drug
(C1D1)
- Planned live vaccine administration after starting study drug (C1D1)
- Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events version
4.0 [CTCAE v4.0]) from acute non-hematologic toxicity (Grade ≤2 neuropathy or
alopecia) due to previous therapy prior to screening
- Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening
(unless secondary to pacemaker or bundle branch block)
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall response rate (ORR) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | ORR, as determined by central review according to the 2014 Lugano classification, defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) |
Secondary Outcome Measures
Measure: | Duration of Response (DOR) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | DOR defined as the time from the first documentation of tumor response to disease progression or death |
Measure: | CR rate |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | CR rate defined as the percentage of treated patients with a BOR of CR |
Measure: | Relapse-free survival (RFS) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | RFS defined as the time from the documentation of CR to disease progression or death |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | PFS defined as the time between start of treatment and the first documentation of recurrence, progression, or death |
Measure: | Overall Survival (OS) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | OS defined as the time between the start of treatment and death from any cause |
Measure: | Frequency and severity of adverse events (AEs) and serious AEs (SAEs) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | |
Measure: | Maximum concentration (Cmax) of Loncastuximab Tesirine , pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Noncompartmental analysis of the maximum concentration (Cmax) |
Measure: | Time to maximum concentration (Tmax) of Loncastuximab Tesirine, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Noncompartmental analysis of the time to maximum concentration (Tmax) |
Measure: | Area under the curve (AUC0-last) of Loncastuximab Tesirine, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-last) |
Measure: | Area under the curve (AUC0-τ) of Loncastuximab Tesirine, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ) |
Measure: | Area under the curve (AUC0-∞) of Loncastuximab Tesirine, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞) |
Measure: | Accumulation index (AI) of Loncastuximab Tesirine, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Noncompartmental analysis of the accumulation index (AI) |
Measure: | Clearance (CL) of Loncastuximab Tesirine, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Noncompartmental analysis of Clearance (CL) |
Measure: | Measurement of Anti-drug antibodies to Loncastuximab Tesirine |
Time Frame: | Blood sample collection within cycles 1 and 2 and every other cycle starting with cycle 3, until disease progression/discontinuation within 30 days of last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | Measurement of Anti-drug antibodies to ADCT-301 before, during and after treatment with Loncastuximab Tesirine |
Measure: | Change from baseline in HRQoL as measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) |
Time Frame: | Day 1 of each cycle until up to 30 days after last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | EQ-5D-5L is designed as an international, standardized, instrument for describing and evaluating QoL. The EQ-5D-5L consists of two parts:
The descriptive system: QoL is classified according to five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises five levels of perceived problems (e.g., none, slight, moderate, severe, extreme).
The visual analog scale (VAS): patients are asked to indicate their health state today on a VAS with the endpoints labeled 'the best health you can imagine' (score 100) and 'the worst health you can imagine' (score 0).Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)(EQ-5D-5L) |
Measure: | Change from baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) |
Time Frame: | Day 1 of each cycle until up to 30 days after last dose (each cycle is 3 weeks) |
Safety Issue: | |
Description: | FACT-Lym is a lymphoma-specific subscale for the Functional Assessment of Cancer Therapy (FACT) questionnaire. It consists of 15 specific items that are used together with the core 27-item questionnaire FACT-G (General). The patient is asked to respond to each item with a score of 0-4, where 0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much. A higher score equals a worse level of QoL. |
Measure: | Changes from baseline of ECOG performance status |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | ECOG (Eastern Cooperative Oncology Group) Performance Status is a 5-point scale, from 0 (fully active) to 5 (dead).
Characterize the safety profile of loncastuximab tesirine. |
Measure: | Changes from baseline of 12-lead electrocardiograms (ECGs) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Characterize the safety profile of loncastuximab tesirine |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | ADC Therapeutics S.A. |
Trial Keywords
Last Updated
June 15, 2020