Non-Hodgkin LymphomaPhase 1NCT02669017
Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
A Phase 1 study testing ADCT-402 in people with Non-Hodgkin Lymphoma and Burkitt's Lymphoma, run by ADC Therapeutics S.A. at 11 sites in 3 countries.
Trial summary
This study evaluates ADCT-402 in participants with Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL). Participants will participate in a dose escalation phase (Part 1) and dose expansion (Part 2). In Part 2, participants will receive the dose level identified in Part 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia
- What is being tested?
- ADCT-402
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 183 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Mar 2016to 21 Feb 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants, ages 18 years or older with pathologically confirmed relapsed or refractory B-cell lineage NHL who have failed or are intolerant to established therapy, or for whom no other treatment options are available.
- Refractory or relapsed B-cell NHL (per World health Organization [WHO] Classification system).
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
- Measurable disease, as defined by the 2014 Lugano Classification.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Absolute neutrophil count (ANC) ≥1000/μL.
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- Platelet count of ≥75000/μL.
- Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
- Serum/plasma creatinine ≤1.5 mg/dL.
- Serum/plasma alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if there is liver or bone involvement.
- Total serum/plasma bilirubin ≤1.5 times ULN.
- Negative blood or urine beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to Day 1 for women of childbearing potential.
- Males, and female participants who are biologically capable of having children, must agree to use a medically acceptable method of birth control.
Who cannot join
- Participants who have any option for other treatment for B-cell NHL at the current state of disease.
- Active graft-versus-host disease.
- Autologous or allogenic transplant within the 60 days prior to the Screening visit.
- Known history of immunogenicity or hypersensitivity to a CD19 antibody.
- Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
- Known history of positive serum human ADA.
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- Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other central nervous system (CNS) autoimmune disease.
- Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV).
- History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
- Pregnant or breastfeeding women.
- Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
- Use of any other experimental medication(s) within 14 days or 5 half-lives but in no case less than 14 days prior to start of study treatment on Cycle 1, Day 1, except if approved by Sponsor.
- Steroid use equivalent to greater than 20 mg of prednisone within 4 weeks (28 days) prior to Day 1.
- Major surgery, chemotherapy, systemic therapy (excluding steroids hydroxyurea steroids, and any targeted small molecules or biologics), or radiotherapy, within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor.
- Failure to recover (to Common Terminology Criteria for Adverse Events [CTCAE] Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.
- Congenital long QT syndrome or a corrected QTc interval ≥450 ms at the Screening visit.
- 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 determined not be exclusionary.
- Any other significant medical illness, abnormality, or condition that would make the participant inappropriate for study participation or put the participant at risk.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States8 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Greenville Health System, Institute for Translational Oncology Research, Clinical Research Unit
Greenville, South Carolina, 29605
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center Herbert Irving Pavilion
New York, New York, 10032
Washington University School of Medicine
St Louis, Missouri, 63110
United Kingdom2 sites
University College London Hospitals
London, NW1 2BU
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official title: A Phase 1 Dose-escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
This study evaluates ADCT-402 in participants with Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL). Participants will participate in a dose escalation phase (Part 1) and dose expansion (Part 2). In Part 2, participants will receive the dose level identified in Part 1.
Read the detailed description
Study ADCT-402-101 is the first clinical study with ADCT-402 in participants with B-cell Non Hodgkin Lymphoma (NHL).
ADCT-402 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.
The study will be conducted in 2 parts. In Part 1 (dose escalation) participants will receive infusions of ADCT-402, at escalating doses. Part 1 will continue until the maximum tolerated dose is determined. In Part 2 (expansion), participants will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee.
For each participant, the study will include a screening period (up to 28 days), a treatment period (until withdrawal), and a follow-up period to assess disease progression and survival for up to 12 months after the last dose of study drug. The total study duration will be dependent on overall participant tolerability to the study drug and response to treatment. It is anticipated that the duration of the entire study (Parts 1 and 2) could be approximately 3 years from first participant treated to last participant completed.
- Conditions
- Non-Hodgkin Lymphoma, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell
- Being tested
- ADCT-402
- Keywords
- Loncastuximab tesirine
- Medical subject headings
- Lymphoma, Non-Hodgkin, Burkitt Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADCT-402Drug
Also called Loncastuximab tesirine, Zynlonta
intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1: ADCT-402 dose escalation | Experimental | In Part 1 (dose escalation) participants will receive intravenous (IV) infusions of ADCT-402 at escalating doses, according to a 3+3 study design. Doses will be escalated from 15 µg/kg to 200 µg/kg on Day 1 of each cycle, with cycle lengths of 3 or 6 weeks. Receives: Drug: ADCT-402 |
| Part 2: ADCT-402 dose expansion | Experimental | In Part 2 (expansion), participants will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee.
Participants will receive intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W). Receives: Drug: ADCT-402 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes:
A hematologic DLT is defined as:
- CTCAE Grade 3 or 4 febrile neutropenia or neutropenic infection.
- CTCAE Grade 4 neutropenia lasting >7 days.
- CTCAE Grade 4 thrombocytopenia.
- CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion.
- CTCAE Grade 4 anemia.
A non-hematologic DLT is defined as:
- CTCAE Grade 4 tumor lysis syndrome (TLS). Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage.
- CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia).
- CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication).
- CTCAE Grade 2 or higher skin ulceration.
Measured: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
Recommended Dose of ADCT-402 for Part 2
The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.
Measured: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participants enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Measured: Day 1 to End of Study (a maximum of 18 months)
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A treatment emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Measured: Day 1 to End of Study (a maximum of 18 months)
Secondary outcomes (14)
Overall Response Rate (ORR)
ORR was defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with ADCT-402, before the start of subsequent anticancer therapy or procedure. Tumor response was assessed using the 2014 Lugano Classification for response.
CR is defined as achieving either of the following:
- Complete metabolic response.
- Complete radiologic response (target node regress to <1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology).
PR is defined as achieving either of the following:
- Partial metabolic response (findings indicate residual disease).
- Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of nonmeasured lesions, spleen regressed by >50% in length and no new lesions).
Measured: Baseline to End of Study (a maximum of 18 months)
Duration of Response (DoR)
DoR is defined among responders (complete response [CR] and partial response [PR]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response.
Disease progression is defined as progressive metabolic disease or one of the follow:
- Target node progression.
- An individual extranodal lesion must be abnormal with length >1.5cm and/or increase of length >50%.
- New or clear progression of nonmeasured lesions.
- Regrowth of previously resolved lesions or new nodes >1.5 cm in length.
- New or recurrent bone marrow involvement.
DoR is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Measured: Baseline to End of Study (a maximum of 18 months)
Overall Survival (OS)
OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause.
OS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Measured: Baseline to End of Study (a maximum of 18 months)
Progression-free Survival (PFS)
PFS is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response.
Disease progression is defined as progressive metabolic disease or one of the follow:
- Target node progression.
- An individual extranodal lesion must be abnormal with length >1.5cm and/or increase of length >50%.
- New or clear progression of nonmeasured lesions.
- Regrowth of previously resolved lesions or new nodes >1.5 cm in length.
- New or recurrent bone marrow involvement.
PFS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Measured: Baseline to End of Study (a maximum of 18 months)
Maximum Observed Serum Concentration (Cmax) for ADCT-402
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402
AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Terminal Half-life (Thalf) of ADCT-402
Thalf of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Apparent Clearance (CL) at Steady State for ADCT-402
CL of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Volume of Distribution at Steady State (Vss) for ADCT-402
Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199).
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Accumulation Index (AI) for ADCT-402
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1 (Q3W schedule: 3 week cycle length; Q6W schedule: 6 week cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached.
Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Measured: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402
Blood serum samples were collected and analysed to determine the presence or absence of ADA.
ADA is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Measured: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2016 (estimated)
- Study startMar 2016
- Primary completion21 Feb 2019
- Study completion21 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADC Therapeutics S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02669017
- Sponsor's protocol ID
- ADCT-402-101
- Other IDs
- 2016-000952-92, 2016
- Status last verified
- Apr 2021
- First submitted
- 21 Jan 2016
- Last updated
- 19 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hess B, Townsend W, Ai W, Stathis A, Solh M, Alderuccio JP, Ungar D, Liao S, Liao L, Khouri L, Zhang X, Boni J. Efficacy and Safety Exposure-Response Analysis of Loncastuximab Tesirine in Patients with B cell non-Hodgkin Lymphoma. AAPS J. 2021 Dec 10;24(1):11. doi: 10.1208/s12248-021-00660-3.
PubMed 34893942Hamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid E, O'Connor OA, Feingold JM, Ardeshna KM, Townsend W, Solh M, Heffner LT, Ungar D, Wang L, Boni J, Havenith K, Qin Y, Kahl BS. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021 May 13;137(19):2634-2645. doi: 10.1182/blood.2020007512.
PubMed 33211842Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Epub 2019 Nov 4.
PubMed 31685491
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose-escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
- ClinicalTrials.gov ID
- NCT02669017
- Acronym / sponsor ID
- ADCT-402-101
- Conditions
- Non-Hodgkin Lymphoma, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell
- Keywords
- Loncastuximab tesirine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- ADC Therapeutics S.A.Industry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- 21 Feb 2019 (actual)
- Study completion
- 21 Feb 2019 (actual)
- First posted
- 29 Jan 2016 (estimated)
- Results
- Posted 13 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates ADCT-402 in participants with Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL). Participants will participate in a dose escalation phase (Part 1) and dose expansion (Part 2). In Part 2, participants will receive the dose level identified in Part 1.
Detailed description
Study ADCT-402-101 is the first clinical study with ADCT-402 in participants with B-cell Non Hodgkin Lymphoma (NHL).
ADCT-402 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.
The study will be conducted in 2 parts. In Part 1 (dose escalation) participants will receive infusions of ADCT-402, at escalating doses. Part 1 will continue until the maximum tolerated dose is determined. In Part 2 (expansion), participants will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee.
For each participant, the study will include a screening period (up to 28 days), a treatment period (until withdrawal), and a follow-up period to assess disease progression and survival for up to 12 months after the last dose of study drug. The total study duration will be dependent on overall participant tolerability to the study drug and response to treatment. It is anticipated that the duration of the entire study (Parts 1 and 2) could be approximately 3 years from first participant treated to last participant completed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1: ADCT-402 dose escalation | Experimental | Drug: ADCT-402In Part 1 (dose escalation) participants will receive intravenous (IV) infusions of ADCT-402 at escalating doses, according to a 3+3 study design. Doses will be escalated from 15 µg/kg to 200 µg/kg on Day 1 of each cycle, with cycle lengths of 3 or 6 weeks. |
| Part 2: ADCT-402 dose expansion | Experimental | Drug: ADCT-402In Part 2 (expansion), participants will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee. Participants will receive intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female participants, ages 18 years or older with pathologically confirmed relapsed or refractory B-cell lineage NHL who have failed or are intolerant to established therapy, or for whom no other treatment options are available.
- Refractory or relapsed B-cell NHL (per World health Organization [WHO] Classification system).
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
- Measurable disease, as defined by the 2014 Lugano Classification.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Key exclusion criteria (18 listed)
- Participants who have any option for other treatment for B-cell NHL at the current state of disease.
- Active graft-versus-host disease.
- Autologous or allogenic transplant within the 60 days prior to the Screening visit.
- Known history of immunogenicity or hypersensitivity to a CD19 antibody.
- Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADCT-402Also: Loncastuximab tesirine, Zynlontaintravenous infusion | Drug | Part 1: ADCT-402 dose escalation, Part 2: ADCT-402 dose expansion |
Primary outcome
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: * CTCAE Grade 3 or 4 febrile neutropenia or neutropenic infection. * CTCAE Grade 4 neutropenia lasting >7 days. * CTCAE Grade 4 thrombocytopenia. * CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion. * CTCAE Grade 4 anemia. A non-hematologic DLT is defined as: * CTCAE Grade 4 tumor lysis syndrome (TLS). Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage. * CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 2 or higher skin ulceration.
Recommended Dose of ADCT-402 for Part 2
Time frame: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Day 1 to End of Study (a maximum of 18 months)
An adverse event (AE) is defined as any untoward medical occurrence in a participants enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
Time frame: Day 1 to End of Study (a maximum of 18 months)
An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A treatment emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
14 secondary outcomes
Overall Response Rate (ORR)
Time frame: Baseline to End of Study (a maximum of 18 months)
Duration of Response (DoR)
Time frame: Baseline to End of Study (a maximum of 18 months)
Overall Survival (OS)
Time frame: Baseline to End of Study (a maximum of 18 months)
Progression-free Survival (PFS)
Time frame: Baseline to End of Study (a maximum of 18 months)
Maximum Observed Serum Concentration (Cmax) for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Terminal Half-life (Thalf) of ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Apparent Clearance (CL) at Steady State for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Volume of Distribution at Steady State (Vss) for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Accumulation Index (AI) for ADCT-402
Time frame: Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402
Time frame: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34893942Hess B, Townsend W, Ai W, Stathis A, Solh M, Alderuccio JP, Ungar D, Liao S, Liao L, Khouri L, Zhang X, Boni J. Efficacy and Safety Exposure-Response Analysis of Loncastuximab Tesirine in Patients with B cell non-Hodgkin Lymphoma. AAPS J. 2021 Dec 10;24(1):11. doi: 10.1208/s12248-021-00660-3.
- Derived from this study: PubMed 33211842Hamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid E, O'Connor OA, Feingold JM, Ardeshna KM, Townsend W, Solh M, Heffner LT, Ungar D, Wang L, Boni J, Havenith K, Qin Y, Kahl BS. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021 May 13;137(19):2634-2645. doi: 10.1182/blood.2020007512.
- Derived from this study: PubMed 31685491Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Epub 2019 Nov 4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ADCT-402 in people with Non-Hodgkin Lymphoma and Burkitt's Lymphoma, run by ADC Therapeutics S.A. at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, United Kingdom, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02669017, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2021.