Clinical Trials Register

Summary
EudraCT Number:	2017-004288-11
Sponsor's Protocol Code Number:	ADCT-402-201
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-09-06
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-004288-11

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase 2 Study of Loncastuximab Tesirine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

A.4.1

Sponsor's protocol code number

ADCT-402-201

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ADC Therapeutics SA
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ADC Therapeutics SA
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ADC Therapeutics SA
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Route de la Corniche, 3B
B.5.3.2	Town/ city	Epalinges
B.5.3.3	Post code	1066
B.5.3.4	Country	Switzerland
B.5.6	E-mail	clinicaltrials@adctherapeutics.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Loncastuximab Tesirine
D.3.2	Product code	ADCT-402
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Loncastuximab Tesirine
D.3.9.2	Current sponsor code	ADCT-402
D.3.9.3	Other descriptive name	ADCT-402
D.3.9.4	EV Substance Code	SUB181458
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Loncastuximab Tesirine
D.3.2	Product code	ADCT-402
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Loncastuximab Tesirine
D.3.9.2	Current sponsor code	ADCT-402
D.3.9.3	Other descriptive name	ADCT-402
D.3.9.4	EV Substance Code	SUB181458
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

E.1.1.1

Medical condition in easily understood language

Diffuse Large B Cell Lymphoma

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the efficacy of single agent loncastuximab tesirine in patients with relapsed or refractory DLBCL

E.2.2

Secondary objectives of the trial

Characterize the safety profile of loncastuximab tesirine
Characterize the pharmacokinetic (PK) profile of loncastuximab tesirine
Evaluate the immunogenicity of loncastuximab tesirine
Evaluate the impact of loncastuximab tesirine treatment on health-related quality of life (HRQoL)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patient aged 18 years or older
2. 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
3. Relapsed or refractory disease following two or more multi-agent systemic treatment regimens
4. Patients who have received previous CD19-directed therapy must have a biopsy that shows CD19 protein expression after completion of the CD19-directed therapy
5. Measurable disease as defined by the 2014 Lugano Classification
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available)
7. ECOG performance status 0-2
8. Adequate organ function as defined by screening laboratory values within the following parameters:
a. Absolute neutrophil count (ANC) ≥1.0 × 10^3/µL (off growth factors at least 72 hours)
b. Platelet count ≥75 × 10^3/µL without transfusion in the prior 7 days
c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN)
d. Total bilirubin ≤1.5 × ULN (patients with known Gilbert’s syndrome may have a total bilirubin up to ≤3 × ULN)
e. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft and Gault equation
9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential
10. 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

E.4

Principal exclusion criteria

1. Previous treatment with loncastuximab tesirine
2. Known history of hypersensitivity to or positive serum human ADA
to a CD19 antibody
3. Pathologic diagnosis of Burkitt lymphoma
4. Bulky disease, defined as any tumor ≥10 cm in longest dimension
5. 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
6. Autologous stem cell transplant within 30 days prior to start of study
drug (C1D1)
7. Allogeneic stem cell transplant within 60 days prior to start of study
drug (C1D1)
8. Active graft-versus-host disease
9. Post-transplant lymphoproliferative disorders
10. Active autoimmune disease, including motor neuropathy considered
of autoimmune origin and other central nervous system (CNS)
autoimmune disease
11. Known seropositive and requiring anti-viral therapy for human
immunodeficiency virus (HIV), hepatitis B virus (HBV), or
hepatitis C virus (HCV). Note: Testing is not mandatory to be
eligible
12. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
13. Lymphoma with active CNS involvement at the time of screening,
including leptomeningeal disease
14. 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)
15. Breastfeeding or pregnant
16. Significant medical comorbidities, including but not limited to,
uncontrolled hypertension (blood pressure [BP] ≥160/100 mmHg
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
17. 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
18. Use of any other experimental medication within 14 days prior to
start of study drug (C1D1)
19. Planned live vaccine administration after starting study drug (C1D1)
20. Failure to recover to Grade ≤1 (Common Terminology Criteria for
Adverse Events [CTCAE] version 4.0) from acute non-hematologictoxicity toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening
21. Congenital long QT syndrome or a corrected QTcF interval of
>480 ms at screening (unless secondary to pacemaker or bundle
branch block)
22. 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

E.5 End points

E.5.1

Primary end point(s)

ORR according to the 2014 Lugano classification as determined by central review in all treated patients; ORR is defined as the proportion of patients with a best overall response (BOR) of CR or PR

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary end point evaluated at 6 and 12 weeks after first dose, then every 9 weeks until disease progression.

E.5.2

Secondary end point(s)

For further evaluation of efficacy of loncastuximab tesirine:
- DOR defined as the time from the first documentation of tumor response to disease progression or death
- CR rate defined as the percentage of treated patients with a BOR of CR
- Relapse-free survival (RFS) defined as the time from the documentation of CR to disease progression or death
- PFS defined as the time between start of treatment and the first documentation of recurrence, progression, or death
- OS defined as the time between the start of treatment and death from any cause
For characterization of safety profile of loncastuximab tesirine:
- Frequency and severity of adverse events (AEs), and SAEs
- Changes from baseline of safety laboratory variables, vital signs, ECOG performance status, and 12-lead electrocardiograms (ECGs)
For characterization of PK profile of loncastuximab tesirine:
- Concentrations and PK parameters of loncastuximab tesirine total antibody, PBD conjugated antibody, and unconjugated warhead SG3199
For evaluation of immunogenicity of loncastuximab tesirine:
- Anti-drug antibody (ADA) titers and, if applicable, neutralizing activity to loncastuximab tesirine after treatment with loncastuximab tesirine
For evaluation of impact of loncastuximab tesirine treatment on health-related quality of life (HRQoL):
- Change from baseline in HRQoL as measured by EuroQol–5 Dimensions–5 Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy - Lymphoma (FACT Lym)

E.5.2.1

Timepoint(s) of evaluation of this end point

There are different timepoints for evaluation of secondary end-points

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Italy

Switzerland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

140

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the subject has ended the participation in the trial, standard treatment by their physician is expected

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-07-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-08-10

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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