Clinical Trials Register

Summary
EudraCT Number:	2020-003695-40
Sponsor's Protocol Code Number:	ADCT-402-202
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-03-08
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2020-003695-40

A.3

Full title of the trial

A Phase 2 Randomized Study of Loncastuximab Tesirine Versus Idelalisib in Patients with Relapsed or Refractory Follicular Lymphoma (LOTIS 6)

A.3.1

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

Study to Evaluate Loncastuximab Tesirine Versus Idelalisib in Patients with Relapsed or Refractory Follicular Lymphoma

A.3.2

Name or abbreviated title of the trial where available

LOTIS 6

A.4.1

Sponsor's protocol code number

ADCT-402-202

A.5.4

Other Identifiers

Name:

IND Number

Number:

126138

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	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.3.9.1	CAS number	1879918-31-6
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	Comparator
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	Yes
D.2.1.1.1	Trade name	Zydelig
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences Ireland UC
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Idelalisib
D.3.2	Product code	Idelalisib
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IDELALISIB
D.3.9.1	CAS number	870281-82-6
D.3.9.4	EV Substance Code	SUB126168
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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 Follicular Lymphoma

E.1.1.1

Medical condition in easily understood language

Lymphoma

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10067070
E.1.2	Term	Follicular B-cell non-Hodgkin's lymphoma
E.1.2	System Organ Class	100000004864

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

To evaluate the efficacy of single agent loncastuximab tesirine compared to idelalisib in patients with relapsed or refractory follicular lymphoma.

E.2.2

Secondary objectives of the trial

To further evaluate the additional efficacy of single agent loncastuximab tesirine compared to idelalisib in patients with relapsed or refractory follicular lymphoma.
To assess the safety profile of loncastuximab tesirine in patients with relapsed or refractory follicular lymphoma.
To characterize the pharmacokinetics (PK) profile of loncastuximab tesirine.
To evaluate the immunogenicity of loncastuximab tesirine.
To evaluate the impact of loncastuximab tesirine treatment compared to idelalisib on patients-reported outcomes (PROs) (e.g., symptoms, functions, and overall health status).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained prior to any study procedures.
2. Male or female patients aged 18 years or older, with pathologic diagnosis of follicular lymphoma (Grade 1, 2, 3A) in the most recent tumor biopsy.
3. Relapsed or refractory disease following two or more treatment regimens, at least one of which must have contained an anti-CD20 therapy.
4.Patients who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy.
5. Measurable disease as defined by the 2014 Lugano Classification as assessed by positron emission tomography-computed tomography (PET CT) or, if not FDG-avid, CT or magnetic resonance imaging (MRI).
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available).
Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred.
7. ECOG performance status 0 to 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 past 2 weeks,
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. Calculated creatinine clearance ≥30 mL/min by the Cockcroft and Gault equation.
Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility
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 6 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 6 months after the patient receives his last dose of study treatment.

E.4

Principal exclusion criteria

1. Previous treatment with loncastuximab tesirine.
2. Previous treatment with idelalisib.
3. Follicular lymphoma which has transformed to diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphoma.
4. Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor, inducer, or sensitive substrate.
5. History of or ongoing drug-induced pneumonitis.
6. History of or ongoing inflammatory bowel disease.
7. Any condition that could interfere with the absorption or metabolism of idelalisib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
8. 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.
9. Autologous transplant within 30 days prior to start of study treatment (C1D1).
10. Allogenic transplant within 60 days prior to start of study treatment (C1D1).
11. Active graft-versus-host disease.
12. Post-transplantation lymphoproliferative disorders.
13. Human immunodeficiency virus (HIV) seropositive with any of the following:
a. CD4+ T-cell counts <350 cells/µL.
b. Acquired immuno-deficiency syndrome (AIDS)-defining opportunistic infection within 12 months prior to screening.
c. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of screening.
d. HIV viral load ≥400 copies/mL.
14. Serologic evidence of chronic hepatitis B infection and unable or unwilling to receive standard prophylactic anti-viral therapy or with detectable hepatitis B virus (HBV) viral load.
15. Serologic evidence of hepatitis C infection without completion of curative treatment or with detectable hepatitis C virus (HCV) viral load.
16. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
17. Lymphoma with active central nervous system involvement, including leptomeningeal disease.
18. 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).
19. Breastfeeding or pregnant.
20. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (BP ≥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.
21. Any Grade ≥3 active infection which requires IV antibiotics, IV antiviral, or IV antifungal treatment.
22. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study treatment (C1D1), except shorter if approved by the Sponsor.
23. Use of any other experimental medication within 30 days prior to start of study treatment (C1D1).
24. Live vaccine administration within 4 weeks prior to Cycle 1 Day 1.
25. Failure to recover to ≤ Grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] v5.0) from acute non-hematologic toxicity (except ≤ Grade 2 neuropathy or alopecia) due to previous therapy prior to screening.
26. 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)

Complete response rate (CRR) according to the 2014 Lugano classification as determined by central review in patients with FL. Complete response rate is the proportion of patients with a best overall response (BOR) of complete response (CR) assessed prior to any subsequent anticancer treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

For Loncastuximab Tesirine arm and Idelalisib arm: Imaging will be performed from screening (Baseline), 6 weeks and 12 weeks after C1D1, then every 12 weeks until 2 years from C1D1, then every 6 months. Imaging for disease assessment will continue until disease progression or initiation of other anti-cancer therapy (except for hematopoietic stem cell transplant).

E.5.2

Secondary end point(s)

Overall response rate (ORR) defined as the percentage of patients with a best overall response (BOR) of complete response (CR) or partial response(PR) by central review assessed prior to any subsequent anticancer treatment. Progression free survival (PFS) defined as the time between the randomization date and the first documentation of recurrence, progression, or death.
Overall survival (OS) defined as the time between the randomization date and death from any cause.
Duration of response (DOR) defined as the time from the documentation of tumor response to disease progression or death.
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Changes from baseline of safety laboratory values, vital signs, 12-lead electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status.
Concentrations and PK parameters of loncastuximab tesirine total antibody, pyrrolobenzodiazepine (PBD)-conjugated antibody, and unconjugated warhead SG3199.
Anti-drug antibody (ADA) titers
Change from baseline in PROs as measured by EuroQol–5 Dimensions–5 Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
The occurrence, severity, and interference of specific symptomatic adverse events selected from Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™)

E.5.2.1

Timepoint(s) of evaluation of this end point

There are different timepoints for the evaluation of the secondary endpoints

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

Yes

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

Yes

E.6.11

Pharmacogenomic

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.3.1

Comparator description

Idelalisib

E.8.2.4

Number of treatment arms in the trial

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

Canada

Israel

United States

Belgium

France

Germany

Hungary

Italy

Poland

Spain

Switzerland

United Kingdom

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

The end of study (EOS) occurs at the last scheduled visit/procedure for the last patient, unless the study is terminated earlier by Sponsor. The death date should be considered as the EOS date for an individual patient whose survival status was informed at any later contact date.

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

125

F.4.2.2

In the whole clinical trial

150

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 patient has ended participation on the study, standard of care 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

2021-05-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-11-25

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