Diffuse Large B-cell Lymphoma Recurrent, Diffuse Large B-Cell Lymphoma Refractory
Conditions
Keywords
Loncastuximab tesirine
Brief summary
The purpose of this Phase 2 study is to evaluate the clinical efficacy and safety of Loncastuximab Tesirine (ADCT-402) in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma.
Detailed description
This is a Phase 2, multi-center, open-label, single-arm study of the efficacy and safety of loncastuximab tesirine used as monotherapy in patients with relapsed or refractory DLBCL. The study will enroll approximately 140 patients Loncastuximab Tesirine is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated through a cathepsin-cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Loncastuximab tesirine has been designed to target and kill CD19-expressing malignant B-cells. A 2-stage design will be used in this clinical study, with an interim analysis for futility on the first 52 patients. If ≥10 patients respond (CR+PR), the study will proceed to complete full enrollment. Enrollment will continue during the interim analysis; however, further enrollment will be halted if futility is confirmed. For each patient, the study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3 weeks), and a Follow-up Period (approximately every 12 week visits for up to 3 years after treatment discontinuation). Patients may continue treatment until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.
Interventions
DRUGLoncastuximab tesirine
intravenous infusion
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patient aged 18 years or older. * Pathologic diagnosis of DLBCL, as defined by the 2016 WHO classification, to include: DLBCL not otherwise specified; primary mediastinal large B-cell lymphoma; and high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements * Relapsed or refractory disease following two or more multi-agent systemic treatment regimens * Patients who have received previous CD19-directed therapy must have a biopsy that shows CD19 protein expression after completion of the CD19-directed therapy. * Measurable disease as defined by the 2014 Lugano Classification * Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block or minimum 10 freshly cut unstained slides if block is not available * ECOG performance status 0-2 * Adequate organ function * Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential * Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the patient receives his last dose of loncastuximab tesirine.
Exclusion criteria
* Previous treatment with loncastuximab tesirine * Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody * Pathologic diagnosis of Burkitt lymphoma * Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary * Autologous stem cell transplant (ASCT) within 30 days prior to start of study drug (C1D1) * Allogeneic stem cell transplant (AlloSCT) within 60 days prior to start of study drug (C1D1) * Active graft-versus-host disease * Post-transplant lymphoproliferative disorders * Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease * Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). * History of Stevens-Johnson syndrome or toxic epidermal necrolysis * Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease * Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath) * Breastfeeding or pregnant * Significant medical comorbidities * Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor * Use of any other experimental medication within 14 days prior to start of study drug (C1D1) * Planned live vaccine administration after starting study drug (C1D1) * Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events version 4.0 \[CTCAE v4.0\]) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening * Congenital long QT syndrome or a corrected QTcF interval of \>480 ms at screening (unless secondary to pacemaker or bundle branch block) * Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 21.5 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | Up to 39 months | CR rate defined as the percentage of treated participants with a best overall response (BOR) of CR. |
| Relapse-free Survival (RFS) | Up to 39 months | RFS was defined as the time from the documentation of CR to disease progression or death. |
| Progression-free Survival (PFS) | Up to 40 months | PFS was defined as the time between start of treatment and the first documentation of recurrence, progression, or death. |
| Overall Survival (OS) | Up to 43 months | OS was defined as the time between the start of treatment and death from any cause. |
| Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Up to 599 days | An adverse event (AE) was defined as any untoward medical occurrence in a patient 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. |
| Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests | Baseline up to 599 days | Clinical laboratory tests included hematology and chemistry. Clinically significant changes were determined by the Investigator. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to 599 days | Vital sign measurements included arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator. |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | Baseline and end of treatment (up to 599 days) | 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 |
| Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs) | Baseline up to 599 days | 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. |
| Duration of Response (DOR) | Up to 39 months | DOR defined as the time from the first documentation of tumor response to disease progression or death. |
| 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 | Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose | — |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose | — |
| Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose | — |
| Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose | — |
| Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose | — |
| Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose | AI is the ratio of AUC0-last for each cycle divided by AUC0-last of the previous cycle. |
| Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | Up to 599 days | — |
| Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Baseline, Day 1 of Cycles 2 to 26 (cycle duration of 3 weeks), and end of treatment (up to 599 days) | 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. |
| Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Baseline, Day 1 of Cycles 2 to 25 (cycle duration of 3 weeks), and end of treatment (up to 599 days) | 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 indicates less symptoms. The LymS score is reported. A positive change from baseline indicates an improvement in health related QoL. |
| Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | 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 | — |
Countries
Italy, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 28 study sites in Italy, Switzerland, the United Kingdom, and the United States from 01 August 2018 to 09 August 2022.
Participants by arm
| Arm | Count |
|---|---|
| Loncastuximab Tesirine 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. | 145 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 97 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Miscellaneous | 1 |
| Overall Study | Physician Decision | 20 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Loncastuximab Tesirine |
|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 13.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaskan Native | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 5 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race Other | 5 Participants |
| Race/Ethnicity, Customized Race White | 130 Participants |
| Region of Enrollment Italy | 53 Participants |
| Region of Enrollment Switzerland | 2 Participants |
| Region of Enrollment United Kingdom | 31 Participants |
| Region of Enrollment United States | 59 Participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 97 / 145 |
| other Total, other adverse events | 139 / 145 |
| serious Total, serious adverse events | 57 / 145 |
Outcome results
Primary
Overall Response Rate (ORR)
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
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Loncastuximab Tesirine | Overall Response Rate (ORR) | 48.3 percentage of participants |
Secondary
Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
AI is the ratio of AUC0-last for each cycle divided by AUC0-last of the previous cycle.
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 2 | 2.07 ratio | Geometric Coefficient of Variation 38.1 |
| Loncastuximab Tesirine | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 2 | 1.65 ratio | Geometric Coefficient of Variation 18.5 |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 1 | — ratio | — |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 3 | — ratio | — |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 1 | — ratio | — |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | SG3199 Cycle 2 | — ratio | — |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | SG3199 Cycle 3 | — ratio | — |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | SG3199 Cycle 1 | — ratio | — |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 3 | — ratio | — |
Secondary
Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 1 | 0.458 L/day | Geometric Coefficient of Variation 47.6 |
| Loncastuximab Tesirine | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 2 | 0.331 L/day | Geometric Coefficient of Variation 32 |
| Loncastuximab Tesirine | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 1 | 0.418 L/day | Geometric Coefficient of Variation 56.5 |
| Loncastuximab Tesirine | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 2 | 0.285 L/day | Geometric Coefficient of Variation 31.3 |
Secondary
Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
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
Population: 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-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 1 | 8.85 days | Geometric Coefficient of Variation 53.5 |
| Loncastuximab Tesirine | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 2 | 15.2 days | Geometric Coefficient of Variation 31.7 |
| Loncastuximab Tesirine | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 1 | 8.66 days | Geometric Coefficient of Variation 54.6 |
| Loncastuximab Tesirine | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 2 | 20.9 days | Geometric Coefficient of Variation 56.5 |
Secondary
Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 1 | 4.24 liters | Geometric Coefficient of Variation 39.6 |
| Loncastuximab Tesirine | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 2 | 6.40 liters | Geometric Coefficient of Variation 36.5 |
| Loncastuximab Tesirine | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 1 | 4.10 liters | Geometric Coefficient of Variation 36.4 |
| Loncastuximab Tesirine | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 2 | 7.54 liters | Geometric Coefficient of Variation 58.9 |
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
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
Population: 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-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 1 | 19825 day*ng/mL | Geometric Coefficient of Variation 52.9 |
| Loncastuximab Tesirine | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 2 | 26902 day*ng/mL | Geometric Coefficient of Variation 33.4 |
| Loncastuximab Tesirine | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 1 | 25778 day*ng/mL | Geometric Coefficient of Variation 61.3 |
| Loncastuximab Tesirine | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 2 | 37761 day*ng/mL | Geometric Coefficient of Variation 30.4 |
Secondary
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
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
Population: 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-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | 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 | Conjugated Antibody Cycle 1 | 15850 day*ng/mL | Geometric Coefficient of Variation 105 |
| Loncastuximab Tesirine | 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 | Conjugated Antibody Cycle 2 | 23913 day*ng/mL | Geometric Coefficient of Variation 67.1 |
| Loncastuximab Tesirine | 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 | Total Antibody Cycle 1 | 22160 day*ng/mL | Geometric Coefficient of Variation 106 |
| Loncastuximab Tesirine | 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 | Total Antibody Cycle 2 | 33762 day*ng/mL | Geometric Coefficient of Variation 67.2 |
| Loncastuximab Tesirine | 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 | SG3199 Cycle 1 | 0.00400 day*ng/mL | Geometric Coefficient of Variation 576 |
| Loncastuximab Tesirine | 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 | SG3199 Cycle 2 | 0.00100 day*ng/mL | Geometric Coefficient of Variation 204 |
Secondary
Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
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, Day 1 of Cycles 2 to 26 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
Population: Patient reported outcome (PRO) population. Only participants with data available for analysis are included. Overall number of participants analyzed prepresents all participants who contributed data to this assessment, though not all participants contributed data to each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 2 Day 1 | -0.1 score on a scale | Standard Deviation 15.97 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 3 Day 1 | 1.3 score on a scale | Standard Deviation 16.85 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 4 Day 1 | 2.8 score on a scale | Standard Deviation 15 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 5 Day 1 | 2.8 score on a scale | Standard Deviation 13.5 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 6 Day 1 | 3.0 score on a scale | Standard Deviation 17.45 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 7 Day 1 | 4.0 score on a scale | Standard Deviation 12.91 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 8 Day 1 | 7.3 score on a scale | Standard Deviation 12.87 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 9 Day 1 | 7.7 score on a scale | Standard Deviation 15.69 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 10 Day 1 | 12.2 score on a scale | Standard Deviation 15.64 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 11 Day 1 | 11.8 score on a scale | Standard Deviation 17.62 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 12 Day 1 | 16.3 score on a scale | Standard Deviation 16.06 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 13 Day 1 | 6.0 score on a scale | Standard Deviation 16.54 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 14 Day 1 | 12.2 score on a scale | Standard Deviation 15.43 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 15 Day 1 | 6.6 score on a scale | Standard Deviation 12.36 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 16 Day 1 | 5.5 score on a scale | Standard Deviation 13.7 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 17 Day 1 | 8.3 score on a scale | Standard Deviation 13.62 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 18 Day 1 | 11.0 score on a scale | Standard Deviation 11.53 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 19 Day 1 | 11.5 score on a scale | Standard Deviation 16.26 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 20 Day 1 | 23.0 score on a scale | — |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 21 Day 1 | 16.5 score on a scale | Standard Deviation 9.19 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 22 Day 1 | 16.5 score on a scale | Standard Deviation 9.19 |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 23 Day 1 | 23.0 score on a scale | — |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 24 Day 1 | 23.0 score on a scale | — |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 25 Day 1 | 23.0 score on a scale | — |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | Cycle 26 Day 1 | 23.0 score on a scale | — |
| Loncastuximab Tesirine | Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) | End of treatment | -8.3 score on a scale | Standard Deviation 19.85 |
Secondary
Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS)
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 indicates less symptoms. The LymS score is reported. A positive change from baseline indicates an improvement in health related QoL.
Time frame: Baseline, Day 1 of Cycles 2 to 25 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
Population: PRO population. Only participants with data available for analysis are included. Overall number of participants analyzed represents all participants who contributed data to this assessment, though not all participants contributed data to each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 2 Day 1 | 0.95 score on a scale | Standard Deviation 7.114 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 3 Day 1 | 1.34 score on a scale | Standard Deviation 8.764 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 4 Day 1 | 2.09 score on a scale | Standard Deviation 8.832 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 5 Day 1 | 0.16 score on a scale | Standard Deviation 8.506 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 6 Day 1 | 1.16 score on a scale | Standard Deviation 9.918 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 7 Day 1 | 1.00 score on a scale | Standard Deviation 11.474 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 8 Day 1 | 3.43 score on a scale | Standard Deviation 10.141 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 9 Day 1 | 2.17 score on a scale | Standard Deviation 9.498 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 10 Day 1 | 3.18 score on a scale | Standard Deviation 11.769 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 11 Day 1 | 4.35 score on a scale | Standard Deviation 13.053 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 12 Day 1 | 4.90 score on a scale | Standard Deviation 11.14 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 13 Day 1 | 2.01 score on a scale | Standard Deviation 16.871 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 14 Day 1 | 0.63 score on a scale | Standard Deviation 17.442 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 15 Day 1 | -3.27 score on a scale | Standard Deviation 7.691 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 16 Day 1 | -8.04 score on a scale | Standard Deviation 10.561 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 17 Day 1 | -6.88 score on a scale | Standard Deviation 9.36 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 18 Day 1 | -5.00 score on a scale | Standard Deviation 7.937 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 19 Day 1 | -1.00 score on a scale | Standard Deviation 4.243 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 20 Day 1 | -2.25 score on a scale | Standard Deviation 4.596 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 21 Day 1 | -0.50 score on a scale | Standard Deviation 2.121 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 22 Day 1 | -1.00 score on a scale | Standard Deviation 2.828 |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 23 Day 1 | 1.00 score on a scale | — |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | Cycle 25 Day 1 | 1.00 score on a scale | — |
| Loncastuximab Tesirine | Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS) | End of treatment | -1.19 score on a scale | Standard Deviation 9.042 |
Secondary
Complete Response (CR) Rate
CR rate defined as the percentage of treated participants with a best overall response (BOR) of CR.
Time frame: Up to 39 months
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Loncastuximab Tesirine | Complete Response (CR) Rate | 24.8 percentage of participants |
Secondary
Duration of Response (DOR)
DOR defined as the time from the first documentation of tumor response to disease progression or death.
Time frame: Up to 39 months
Population: Participants in the all-treated population who achieved a complete response (CR) or partial response (PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Loncastuximab Tesirine | Duration of Response (DOR) | 13.37 months |
Secondary
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
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 and end of treatment (up to 599 days)
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | Baseline | ECOG score 0 | 58 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | Baseline | ECOG score 1 | 78 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | Baseline | ECOG score 2 | 9 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | Baseline | ECOG score 3 | 0 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | Baseline | ECOG score 4 | 0 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | Baseline | ECOG score 5 | 0 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | End of treatment | ECOG score 0 | 44 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | End of treatment | ECOG score 1 | 50 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | End of treatment | ECOG score 2 | 14 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | End of treatment | ECOG score 3 | 2 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | End of treatment | ECOG score 4 | 1 Participants |
| Loncastuximab Tesirine | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment | End of treatment | ECOG score 5 | 0 Participants |
Secondary
Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
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
Population: 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-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 1 | 2430 ng/mL | Geometric Coefficient of Variation 38.8 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 2 | 2734 ng/mL | Geometric Coefficient of Variation 35.8 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Conjugated Antibody Cycle 3 | 1694 ng/mL | Geometric Coefficient of Variation 47.6 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 1 | 3267 ng/mL | Geometric Coefficient of Variation 36.7 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 2 | 3756 ng/mL | Geometric Coefficient of Variation 31.3 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Total Antibody Cycle 3 | 2581 ng/mL | Geometric Coefficient of Variation 41.9 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | SG3199 Cycle 1 | 0.0410 ng/mL | Geometric Coefficient of Variation 56.6 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | SG3199 Cycle 2 | 0.0490 ng/mL | Geometric Coefficient of Variation 78.8 |
| Loncastuximab Tesirine | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | SG3199 Cycle 3 | 0.0320 ng/mL | Geometric Coefficient of Variation 20.3 |
Secondary
Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a patient 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 599 days
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Loncastuximab Tesirine | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 143 Participants |
| Loncastuximab Tesirine | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Grade ≥3 TEAE | 107 Participants |
| Loncastuximab Tesirine | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 57 Participants |
Secondary
Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine
Time frame: Up to 599 days
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Loncastuximab Tesirine | Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | Confirmed Positive ADA Pre-dose | 1 Participants |
| Loncastuximab Tesirine | Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | Confirmed Positive ADA Post-dose Only | 0 Participants |
| Loncastuximab Tesirine | Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | Confirmed Positive ADA Anytime | 1 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs)
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 up to 599 days
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Loncastuximab Tesirine | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs) | QTcB maximum change from baseline: >30, <=60 msec | 30 Participants |
| Loncastuximab Tesirine | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs) | QTcB maximum change from baseline: >60 msec | 4 Participants |
| Loncastuximab Tesirine | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs) | QTcF maximum change from baseline: >30, <=60 msec | 23 Participants |
| Loncastuximab Tesirine | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs) | QTcF maximum change from baseline: >60 msec | 1 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital sign measurements included arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
Time frame: Baseline up to 599 days
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loncastuximab Tesirine | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
Clinical laboratory tests included hematology and chemistry. Clinically significant changes were determined by the Investigator.
Time frame: Baseline up to 599 days
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loncastuximab Tesirine | Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests | 83 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time between the start of treatment and death from any cause.
Time frame: Up to 43 months
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Loncastuximab Tesirine | Overall Survival (OS) | 9.53 months |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time between start of treatment and the first documentation of recurrence, progression, or death.
Time frame: Up to 40 months
Population: All-treated population - all participants who received at least 1 dose of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Loncastuximab Tesirine | Progression-free Survival (PFS) | 4.93 months |
Secondary
Relapse-free Survival (RFS)
RFS was defined as the time from the documentation of CR to disease progression or death.
Time frame: Up to 39 months
Population: Participants in the all-treated population who achieved CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Loncastuximab Tesirine | Relapse-free Survival (RFS) | NA months |