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Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (LOTIS-2)

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ClinicalTrials.gov Identifier: NCT03589469
Recruitment Status : Active, not recruiting
First Posted : July 18, 2018
Results First Posted : July 29, 2021
Last Update Posted : July 29, 2021
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics S.A.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diffuse Large B-Cell Lymphoma Refractory
Diffuse Large B-cell Lymphoma Recurrent
Intervention Drug: Loncastuximab tesirine
Enrollment 145
Recruitment Details Participants were enrolled at 28 study sites in Italy, Switzerland, the United Kingdom, and the United States from 01 August 2018. Data in this record is for the primary analysis with a data cut-off date of 15 May 2020. Participants are currently still ongoing in this study with an expected study completion date of January 2023.
Pre-assignment Details  
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description Participants received loncastuximab tesirine as an intravenous (IV) infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg once every 3 weeks (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 occurred first.
Period Title: Overall Study
Started 145
Received Treatment 145
Completed 0
Not Completed 145
Reason Not Completed
Ongoing in study             58
Withdrawal by Subject             6
Physician Decision             1
Death             77
Lost to Follow-up             3
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description Participants received 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 occurred first.
Overall Number of Baseline Participants 145
Hide Baseline Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 145 participants
62.7  (13.63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants
Female
60
  41.4%
Male
85
  58.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants
Hispanic or Latino
13
   9.0%
Not Hispanic or Latino
132
  91.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 145 participants
White
130
  89.7%
Black or African American
5
   3.4%
Asian
3
   2.1%
American Indian or Alaskan Native
1
   0.7%
Native Hawaiian or Pacific Islander
1
   0.7%
Other
5
   3.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants
United States
59
  40.7%
United Kingdom
31
  21.4%
Italy
53
  36.6%
Switzerland
2
   1.4%
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR, as determined by central review according to the 2014 Lugano classification, defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).
Time Frame Up to 21.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
48.3
(39.9 to 56.7)
2.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR defined as the time from the first documentation of tumor response to disease progression or death.
Time Frame Up to 21.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the all-treated population who achieved a complete response (CR) or partial response (PR).
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 70
Median (95% Confidence Interval)
Unit of Measure: months
10.25 [1] 
(6.87 to NA)
[1]
Insufficient number of participants with events.
3.Secondary Outcome
Title Complete Response (CR) Rate
Hide Description CR rate defined as the percentage of treated participants with a best overall response (BOR) of CR.
Time Frame Up to 21.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.1
(17.4 to 31.9)
4.Secondary Outcome
Title Relapse-free Survival (RFS)
Hide Description RFS was defined as the time from the documentation of complete response (CR) to disease progression or death.
Time Frame Up to 21.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the all-treated population who achieved CR.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 35
Median (95% Confidence Interval)
Unit of Measure: months
13.37 [1] 
(10.25 to NA)
[1]
Insufficient number of participants with events.
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time between start of treatment and the first documentation of recurrence, progression, or death.
Time Frame Up to 21.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Median (95% Confidence Interval)
Unit of Measure: months
4.93
(2.89 to 8.31)
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time between the start of treatment and death from any cause.
Time Frame Up to 21.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Median (95% Confidence Interval)
Unit of Measure: months
9.92
(6.74 to 11.47)
7.Secondary Outcome
Title Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
Hide Description

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with treatment. A TEAE was an adverse event with an onset that began or worsened on or after the first dose date and until 30 days after the last dose date, or start of a new anticancer therapy/procedure, whichever came earlier. TEAE assessments also included those per the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade ≥3 AEs and serious TEAEs.

AEs were graded using CTCAE version 4 and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. For events not listed in the CTCAE criteria, the same grading was used.

Time Frame Up to 21.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
143
  98.6%
Grade ≥3 TEAE
105
  72.4%
Serious TEAE
57
  39.3%
8.Secondary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
Hide Description Clinical laboratory tests included hematology and chemistry. Clinically significant changes were determined by the Investigator.
Time Frame Baseline to end of treatment (up to 30 days after the last dose) or data cut off: Maximum treatment duration time at date of primary analysis was 351 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Count of Participants
Unit of Measure: Participants
82
  56.6%
9.Secondary Outcome
Title Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Hide Description Vital sign measurements included arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
Time Frame Baseline to end of treatment (up to 30 days after the last dose) or data cut off. Maximum treatment duration time at date of primary analysis was 351 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
10.Secondary Outcome
Title Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
Hide Description

ECOG (Eastern Cooperative Oncology Group) Performance Status is scored on a 6-point scale where higher scores indicate a worse outcome. ECOG scores include the following:

  • 0 = fully active, able to carry on all pre-disease performance without restriction
  • 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  • 2 = ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
  • 3 = capable of only limited self-care; confined to bed or chair more than 50% of waking hours
  • 4 = completely disabled; cannot carry on any self-care; totally confined to bed or chair
  • 5 = dead
Time Frame Baseline to end of treatment (up to 30 days after the last dose) or data cut off. Maximum treatment duration time at date of primary analysis was 351 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment. Results are presented for participants with data available for analysis at end of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 145 participants
ECOG score 0
58
  40.0%
ECOG score 1
78
  53.8%
ECOG score 2
9
   6.2%
ECOG score 3
0
   0.0%
ECOG score 4
0
   0.0%
ECOG score 5
0
   0.0%
End of treatment Number Analyzed 105 participants
ECOG score 0
39
  37.1%
ECOG score 1
49
  46.7%
ECOG score 2
14
  13.3%
ECOG score 3
2
   1.9%
ECOG score 4
1
   1.0%
ECOG score 5
0
   0.0%
11.Secondary Outcome
Title Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs)
Hide Description Clinically significant changes from baseline for 12-lead ECGs were measured as abnormal QT interval corrected by Fridericia formula (QTcF) and QT interval corrected by Bazett formula (QTcB) values.
Time Frame Baseline to end of treatment (up to 30 days after the last dose) or data cut off. Maximum treatment duration time at date of primary analysis was 351 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Count of Participants
Unit of Measure: Participants
QTcB maximum change from baseline (msec): >30, <=60
31
  21.4%
QTcB maximum change from baseline (msec): > 60
4
   2.8%
QTcF maximum change from baseline (msec): >30, <=60
23
  15.9%
QTcF maximum change from baseline (msec): >60
1
   0.7%
12.Secondary Outcome
Title Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Hide Description [Not Specified]
Time Frame Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose and end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cyle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 142
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Conjugated Antibody Cycle 1 Number Analyzed 142 participants
2430
(38.8%)
Conjugated Antibody Cycle 2 Number Analyzed 117 participants
2734
(35.8%)
Conjugated Antibody Cycle 3 Number Analyzed 83 participants
1694
(47.6%)
Total Antibody Cycle 1 Number Analyzed 142 participants
3267
(36.7%)
Total Antibody Cycle 2 Number Analyzed 117 participants
3756
(31.3%)
Total Antibody Cycle 3 Number Analyzed 81 participants
2581
(41.9%)
SG3199 Cycle 1 Number Analyzed 8 participants
0.0410
(56.6%)
SG3199 Cycle 2 Number Analyzed 5 participants
0.0490
(78.8%)
SG3199 Cycle 3 Number Analyzed 3 participants
0.0320
(20.3%)
13.Secondary Outcome
Title Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Hide Description [Not Specified]
Time Frame Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cyle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 143
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*ng/mL
Conjugated Antibody Cycle 1 Number Analyzed 143 participants
15850
(105%)
Conjugated Antibody Cycle 2 Number Analyzed 116 participants
23913
(67.1%)
Conjugated Antibody Cycle 3 Number Analyzed 0 participants
Total Antibody Cycle 1 Number Analyzed 143 participants
22160
(106%)
Total Antibody Cycle 2 Number Analyzed 116 participants
33762
(67.2%)
Total Antibody Cycle 3 Number Analyzed 0 participants
SG3199 Cycle 1 Number Analyzed 8 participants
0.00400
(576%)
SG3199 Cycle 2 Number Analyzed 5 participants
0.00100
(204%)
SG3199 Cycle 3 Number Analyzed 0 participants
14.Secondary Outcome
Title Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Hide Description [Not Specified]
Time Frame Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cyle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 99
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*ng/mL
Conjugated Antibody Cycle 1 Number Analyzed 32 participants
19825
(52.9%)
Conjugated Antibody Cycle 2 Number Analyzed 99 participants
26902
(33.4%)
Conjugated Antibody Cycle 3 Number Analyzed 0 participants
Total Antibody Cycle 1 Number Analyzed 27 participants
25778
(61.3%)
Total Antibody Cycle 2 Number Analyzed 97 participants
37761
(30.4%)
Total Antibody Cycle 3 Number Analyzed 0 participants
SG3199 Cycle 1 Number Analyzed 0 participants
SG3199 Cycle 2 Number Analyzed 0 participants
SG3199 Cycle 3 Number Analyzed 0 participants
15.Secondary Outcome
Title Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Hide Description Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)
Time Frame Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cyle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 90
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day
Conjugated Antibody Cycle 1 Number Analyzed 32 participants
8.85
(53.5%)
Conjugated Antibody Cycle 2 Number Analyzed 90 participants
15.2
(31.7%)
Conjugated Antibody Cycle 3 Number Analyzed 0 participants
Total Antibody Cycle 1 Number Analyzed 27 participants
8.66
(54.6%)
Total Antibody Cycle 2 Number Analyzed 63 participants
20.9
(56.5%)
Total Antibody Cycle 3 Number Analyzed 0 participants
SG3199 Cycle 1 Number Analyzed 0 participants
SG3199 Cycle 2 Number Analyzed 0 participants
SG3199 Cycle 3 Number Analyzed 0 participants
16.Secondary Outcome
Title Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Hide Description [Not Specified]
Time Frame Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cyle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 99
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/day
Conjugated Antibody Cycle 1 Number Analyzed 32 participants
0.458
(47.6%)
Conjugated Antibody Cycle 2 Number Analyzed 99 participants
0.331
(32.0%)
Total Antibody Cycle 1 Number Analyzed 27 participants
0.418
(56.5%)
Total Antibody Cycle 2 Number Analyzed 97 participants
0.285
(31.3%)
SG3199 Cycle 1 Number Analyzed 0 participants
SG3199 Cycle 2 Number Analyzed 0 participants
17.Secondary Outcome
Title Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Hide Description [Not Specified]
Time Frame Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cyle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 90
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
Conjugated Antibody Cycle 1 Number Analyzed 32 participants
4.24
(39.6%)
Conjugated Antibody Cycle 2 Number Analyzed 90 participants
6.40
(36.5%)
Conjugated Antibody Cycle 3 Number Analyzed 0 participants
Total Antibody Cycle 1 Number Analyzed 27 participants
4.10
(36.4%)
Total Antibody Cycle 2 Number Analyzed 63 participants
7.54
(58.9%)
Total Antibody Cycle 3 Number Analyzed 0 participants
SG3199 Cycle 1 Number Analyzed 0 participants
SG3199 Cycle 2 Number Analyzed 0 participants
SG3199 Cycle 3 Number Analyzed 0 participants
18.Secondary Outcome
Title Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Hide Description [Not Specified]
Time Frame Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre- Cyle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 90
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
Conjugated Antibody Cycle 1 Number Analyzed 0 participants
Conjugated Antibody Cycle 2 Number Analyzed 90 participants
1.65
(18.5%)
Conjugated Antibody Cycle 3 Number Analyzed 0 participants
Total Antibody Cycle 1 Number Analyzed 0 participants
Total Antibody Cycle 2 Number Analyzed 63 participants
2.07
(38.1%)
Total Antibody Cycle 3 Number Analyzed 0 participants
SG3199 Cycle 1 Number Analyzed 0 participants
SG3199 Cycle 2 Number Analyzed 0 participants
SG3199 Cycle 3 Number Analyzed 0 participants
19.Secondary Outcome
Title Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 to end of treatment or data cut off. Maximum treatment duration time at date of primary analysis was 351 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated population - all participants who received at least 1 dose of treatment.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 145
Measure Type: Count of Participants
Unit of Measure: Participants
Confirmed Positive ADA Pre-dose
1
   0.7%
Confirmed Positive ADA Post-dose Only
0
   0.0%
Confirmed Positive ADA Anytime
1
   0.7%
20.Secondary Outcome
Title Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
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EQ-5D-5L is designed as an international, standardized, instrument for describing and evaluating quality of life (QoL). In the EQ-5D-5L VAS participants 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).

A higher score on the VAS indicates better health related QoL. A positive change from baseline indicates an improvement in health related QoL

Time Frame Baseline to end of treatment (up to 30 days after the last dose) or data cut off. Maximum treatment duration time at date of primary analysis was 351 days.
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Hide Analysis Population Description
Patient reported outcome (PRO) population. Only participants with data available for analysis are included.
Arm/Group Title Loncastuximab Tesirine
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Participants received 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 occurred first.
Overall Number of Participants Analyzed 130
Mean (Standard Deviation)
Unit of Measure: score on a scale
Cycle 2 Number Analyzed 108 participants
-0.1  (15.97)
Cycle 3 Number Analyzed 76 participants
1.3  (16.85)
Cycle 4 Number Analyzed 58 participants
2.8  (15.00)
Cycle 5 Number Analyzed 44 participants
2.8  (13.50)
Cycle 6 Number Analyzed 33 participants
3.0  (17.45)
Cycle 7 Number Analyzed 28 participants
4.0  (12.91)
Cycle 8 Number Analyzed 22 participants
7.3  (12.87)
Cycle 9 Number Analyzed 20 participants
7.7  (15.69)
Cycle 10 Number Analyzed 12 participants
13.2  (15.88)
Cycle 11 Number Analyzed 9 participants
15.1  (19.02)
Cycle 12 Number Analyzed 8 participants
19.1  (16.70)
Cycle 13 Number Analyzed 6 participants
10.5  (16.23)
Cycle 14 Number Analyzed 4 participants
NA [1]   (NA)
Cycle 15 Number Analyzed 1 participants
NA [1]   (NA)
End of treatment Number Analyzed 91 participants
-8.7  (20.15)
[1]
No summary statistics are available given the limited data from the small number of evaluable patients.
21.Secondary Outcome
Title Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS)
Hide Description Composed of the Functional Assessment of Cancer Therapy - General (FACT-G) plus the 15-item LymS. The FACT-G questionnaire contains 27 items covering 4 core health related quality of life (QoL) subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The LymS addresses issues including pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. Score range for the LymS was 0 - 60, where a higher score indicate less symptoms. The LymS score is reported. A positive change from baseline indicates an improvement in health related QoL.
Time Frame Baseline to end of treatment (up to 30 days after the last dose) or data cut off. Maximum treatment duration time at date of primary analysis was 351 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Patient reported outcome (PRO) population. Only participants with data available for analysis are included.
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description:
Participants received 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 occurred first.
Overall Number of Participants Analyzed 130
Mean (Standard Deviation)
Unit of Measure: score on a scale
Cycle 2 Number Analyzed 110 participants
0.95  (7.114)
Cycle 3 Number Analyzed 78 participants
1.34  (8.764)
Cycle 4 Number Analyzed 60 participants
2.09  (8.832)
Cycle 5 Number Analyzed 47 participants
0.16  (8.506)
Cycle 6 Number Analyzed 33 participants
1.16  (9.918)
Cycle 7 Number Analyzed 29 participants
1.00  (11.474)
Cycle 8 Number Analyzed 22 participants
3.43  (10.141)
Cycle 9 Number Analyzed 20 participants
2.17  (9.498)
Cycle 10 Number Analyzed 12 participants
3.20  (12.292)
Cycle 11 Number Analyzed 9 participants
7.04  (14.103)
Cycle 12 Number Analyzed 8 participants
5.63  (12.466)
Cycle 13 Number Analyzed 6 participants
5.62  (16.851)
Cycle 14 Number Analyzed 4 participants
NA [1]   (NA)
Cycle 15 Number Analyzed 1 participants
NA [1]   (NA)
End of treatment Number Analyzed 91 participants
-1.13  (9.183)
[1]
No summary statistics are available given the limited data from the small number of evaluable patients.
Time Frame Up to 21.5 months
Adverse Event Reporting Description All non-serious AEs at a frequency threshold of >=5% and all SAEs, regardless of relationship to study drug, will be reported from the time the patient signs the ICF until 30 days after the last dose of study drug or start of new anti-cancer therapy, whichever is earlier; thereafter, only related SAEs will be reported, with 2 exceptions of subsequent stem cell transplant (SCT) and chimeric antigen receptor T-cell (CAR-T) therapy.
 
Arm/Group Title Loncastuximab Tesirine
Hide Arm/Group Description Participants received 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 occurred first.
All-Cause Mortality
Loncastuximab Tesirine
Affected / at Risk (%)
Total   77/145 (53.10%) 
Hide Serious Adverse Events
Loncastuximab Tesirine
Affected / at Risk (%)
Total   57/145 (39.31%) 
Blood and lymphatic system disorders   
Febrile neutropenia * 1  5/145 (3.45%) 
Anaemia * 1  2/145 (1.38%) 
Neutropenia * 1  1/145 (0.69%) 
Cardiac disorders   
Pericardial effusion * 1  2/145 (1.38%) 
Pericarditis * 1  1/145 (0.69%) 
Gastrointestinal disorders   
Abdominal pain * 1  3/145 (2.07%) 
Ascites * 1  1/145 (0.69%) 
Diarrhoea * 1  1/145 (0.69%) 
Dysphagia * 1  1/145 (0.69%) 
Intestinal obstruction * 1  1/145 (0.69%) 
Small intestinal obstruction * 1  1/145 (0.69%) 
Small intestinal perforation * 1  1/145 (0.69%) 
General disorders   
Pyrexia * 1  4/145 (2.76%) 
Non-cardiac chest pain * 1  2/145 (1.38%) 
Disease progression * 1  1/145 (0.69%) 
Face oedema * 1  1/145 (0.69%) 
Fatigue * 1  1/145 (0.69%) 
Oedema peripheral * 1  1/145 (0.69%) 
Pain * 1  1/145 (0.69%) 
Infections and infestations   
Pneumonia * 1  2/145 (1.38%) 
Escherichia sepsis * 1  1/145 (0.69%) 
Influenza * 1  1/145 (0.69%) 
Klebsiella infection * 1  1/145 (0.69%) 
Lung infection * 1  1/145 (0.69%) 
Metapneumovirus infection * 1  1/145 (0.69%) 
Pneumonia fungal * 1  1/145 (0.69%) 
Rhinovirus infection * 1  1/145 (0.69%) 
Sepsis * 1  1/145 (0.69%) 
Septic shock * 1  1/145 (0.69%) 
Soft tissue infection * 1  1/145 (0.69%) 
Urinary tract infection bacterial * 1  1/145 (0.69%) 
Injury, poisoning and procedural complications   
Fall * 1  1/145 (0.69%) 
Metabolism and nutrition disorders   
Hypercalcaemia * 1  6/145 (4.14%) 
Dehydration * 1  1/145 (0.69%) 
Hyponatraemia * 1  1/145 (0.69%) 
Musculoskeletal and connective tissue disorders   
Neck pain * 1  1/145 (0.69%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Diffuse large B-cell lymphoma * 1  1/145 (0.69%) 
Nervous system disorders   
Headache * 1  2/145 (1.38%) 
Facial nerve disorder * 1  1/145 (0.69%) 
Psychomotor skills impaired * 1  1/145 (0.69%) 
Syncope * 1  1/145 (0.69%) 
Psychiatric disorders   
Mental status changes * 1  2/145 (1.38%) 
Confusional state * 1  1/145 (0.69%) 
Intentional self-injury * 1  1/145 (0.69%) 
Renal and urinary disorders   
Acute kidney injury * 1  2/145 (1.38%) 
Hydronephrosis * 1  1/145 (0.69%) 
Ureterolithiasis * 1  1/145 (0.69%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion * 1  3/145 (2.07%) 
Cough * 1  1/145 (0.69%) 
Dyspnoea * 1  1/145 (0.69%) 
Haemoptysis * 1  1/145 (0.69%) 
Pleuritic pain * 1  1/145 (0.69%) 
Pneumonitis * 1  1/145 (0.69%) 
Vascular disorders   
Deep vein thrombosis * 1  1/145 (0.69%) 
Embolism * 1  1/145 (0.69%) 
Haematoma * 1  1/145 (0.69%) 
Hypotension * 1  1/145 (0.69%) 
Thrombosis * 1  1/145 (0.69%) 
1
Term from vocabulary, MedDRA (22.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Loncastuximab Tesirine
Affected / at Risk (%)
Total   138/145 (95.17%) 
Blood and lymphatic system disorders   
Neutropenia * 1  57/145 (39.31%) 
Thrombocytopenia * 1  48/145 (33.10%) 
Anaemia * 1  38/145 (26.21%) 
Leukopenia * 1  21/145 (14.48%) 
Lymphopenia * 1  11/145 (7.59%) 
Cardiac disorders   
Tachycardia * 1  11/145 (7.59%) 
Gastrointestinal disorders   
Nausea * 1  34/145 (23.45%) 
Diarrhoea * 1  25/145 (17.24%) 
Vomiting * 1  19/145 (13.10%) 
Constipation * 1  17/145 (11.72%) 
Abdominal pain * 1  15/145 (10.34%) 
General disorders   
Fatigue * 1  39/145 (26.90%) 
Oedema peripheral * 1  28/145 (19.31%) 
Pyrexia * 1  25/145 (17.24%) 
Asthenia * 1  14/145 (9.66%) 
Investigations   
Gamma-glutamyltransferase increased * 1  59/145 (40.69%) 
Blood alkaline phosphatase increased * 1  29/145 (20.00%) 
Alanine aminotransferase increased * 1  23/145 (15.86%) 
Aspartate aminotransferase increased * 1  23/145 (15.86%) 
Weight increased * 1  10/145 (6.90%) 
Metabolism and nutrition disorders   
Hypophosphataemia * 1  23/145 (15.86%) 
Decreased appetite * 1  22/145 (15.17%) 
Hypokalaemia * 1  22/145 (15.17%) 
Hypomagnesaemia * 1  20/145 (13.79%) 
Hypocalcaemia * 1  12/145 (8.28%) 
Hyperglycaemia * 1  11/145 (7.59%) 
Hyponatraemia * 1  9/145 (6.21%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  9/145 (6.21%) 
Pain in extremity * 1  9/145 (6.21%) 
Neck pain * 1  8/145 (5.52%) 
Nervous system disorders   
Headache * 1  15/145 (10.34%) 
Dizziness * 1  9/145 (6.21%) 
Psychiatric disorders   
Insomnia * 1  16/145 (11.03%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  31/145 (21.38%) 
Dyspnoea * 1  17/145 (11.72%) 
Pleural effusion * 1  13/145 (8.97%) 
Skin and subcutaneous tissue disorders   
Rash * 1  19/145 (13.10%) 
Pruritus * 1  18/145 (12.41%) 
Erythema * 1  15/145 (10.34%) 
Photosensitivity reaction * 1  15/145 (10.34%) 
Rash maculo-papular * 1  8/145 (5.52%) 
Vascular disorders   
Hypotension * 1  10/145 (6.90%) 
Hypertension * 1  8/145 (5.52%) 
1
Term from vocabulary, MedDRA (22.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI can publish after first multi-site publication or if no multi-site publication is made within 18 months of study completion/termination. The only disclosure restriction on PI is sponsor can review results comms. prior to public release and can embargo comms. regarding trial results for a period >60 but ≤180 days from time submitted to sponsor review. Sponsor can't require changes to the comms, extend embargo or require changes to comms, except removing confidential info that are not results
Results Point of Contact
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Name/Title: Clinical Trials Information
Organization: ADC Therapeutics SA
Phone: 954-903-7994 ext 954
EMail: clinical.trials@adctherapeutics.com
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Responsible Party: ADC Therapeutics S.A.
ClinicalTrials.gov Identifier: NCT03589469    
Other Study ID Numbers: ADCT-402-201
2017-004288-11 ( EudraCT Number )
First Submitted: May 4, 2018
First Posted: July 18, 2018
Results First Submitted: May 20, 2021
Results First Posted: July 29, 2021
Last Update Posted: July 29, 2021