Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma
Conditions
Keywords
Loncastuximab Tesirine in Combination with Ibrutinib
Brief summary
The purpose of this Phase 1/2 study is to evaluate the safety and efficacy of Loncastuximab Tesirine (ADCT-402) in combination with Ibrutinib in participants with Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma.
Detailed description
The Phase 1 portion of the study will cover the dose escalation portion of the study. This will then be followed by the Phase 2 portion of the study, which will treat participants with the dose of loncastuximab tesirine determined in the Phase 1 portion of the study. The ibrutinib dose of 560 mg daily, will remain the same throughout both phases of the study. A standard 3+3 dose escalation design will be used for the Phase 1 portion of the study. The dose-limiting toxicity (DLT) period will be the 21 days following the first dose of ibrutinib. The dose escalation cohort will receive loncastuximab tesirine for 2 cycles with concurrent ibrutinib (concomitant therapy) and may then continue ibrutinib therapy up to one year. The Phase 2 portion of the study will involve 3 cohorts: * Non-germinal center B-cell diffuse large B-cell lymphoma (Non-GCB DLBCL) cohort * Germinal center B-cell diffuse large B-cell lymphoma (GCB DLBCL) cohort * Mantle cell lymphoma (MCL) cohort Each of the cohorts will be treated with the recommended dose of loncastuximab tesirine determined in the Phase 1 portion of the study. The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3 to 4 weeks), and a Follow-up Period (approximately every 12 week visits for up to 2 years after treatment discontinuation).
Interventions
DRUGLoncastuximab Tesirine
Intravenous (IV) infusion.
DRUGIbrutinib
Oral capsule.
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participant aged 18 years or older 2. Pathologic diagnosis of DLBCL or MCL (For Italy Sites Only: MCL patients are excluded.) 3. Participants with DLBCL must have relapsed or refractory disease and have failed or been intolerant to available standard therapy 4. Participants with MCL must have relapsed or refractory disease and have received at least one prior line of therapy (For Italy Sites Only: This exclusion criterion is not applicable) 5. Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy 6. Measurable disease as defined by the 2014 Lugano Classification 7. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available) 8. ECOG performance status 0 to 2 9. Screening laboratory values within the following parameters: 1. Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth factors at least 72 hours) 2. Platelet count ≥75 × 103/µL without transfusion in the past 7 days 3. Hemoglobin ≥8 g/dL (4.96 mmol/L), transfusion allowed 4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the ULN 5. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN) 6. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft and Gault equation 10. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drugs on C1D1 for women of childbearing potential 11. Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of loncastuximab tesirine or 1 month after last dose of ibrutinib, whichever comes last. 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 6 months after the participant receives his last dose of loncastuximab tesirine or 3 months after last dose of ibrutinib, whichever comes last
Exclusion criteria
1. Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a CD19 antibody 2. Known history of hypersensitivity to ibrutinib 3. Previous therapy with ibrutinib or other BTK inhibitors 4. Previous therapy with loncastuximab tesirine 5. Requires treatment or prophylaxis with a moderate or strong cytochrome P450 (CYP) 3A inhibitor 6. Allogenic or autologous transplant within 60 days prior to start of study drugs (C1D1) 7. Active graft-versus-host disease 8. Post-transplantation lymphoproliferative disorder 9. Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease 10. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). 11. History of Stevens-Johnson syndrome or toxic epidermal necrolysis 12. Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease 13. 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) 14. Breastfeeding or pregnant 15. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure \[BP\] ≥160/100 millimeters of mercury (mmHg) repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes mellitus, or severe chronic pulmonary disease, or tuberculosis infection (tuberculosis screening based on local standards). 16. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drugs (C1D1), except shorter if approved by the Sponsor 17. Use of any other experimental medication within 14 days prior to start of study drugs (C1D1) 18. Planned live vaccine administration after starting study drugs (C1D1) 19. Any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel 20. Inherited or acquired bleeding disorders 21. Ongoing anticoagulation treatment, except for low-dose heparinisation or equivalent 22. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 4.0) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening 23. Congenital long QT syndrome or a corrected QTcF interval of \>480 ms at screening (unless secondary to pacemaker or bundle branch block) 24. 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 25. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the participant inappropriate for study participation or put the participant at risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total) | A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes form baseline in safety laboratory values, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and 12-lead electrocardiograms (ECGs) which occurred after first dose of study drug were recorded as TEAEs. |
| Phase 1: Number of Participants With Serious TEAEs | Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total) | A serious TEAE was defined as any AE which occurred after the first dose of study drug that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance was not considered a serious adverse event), resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or important medical events that did not meet the preceding criteria but based on appropriate medical judgement may have jeopardized the participant or may have required medical or surgical intervention to prevent any of the outcomes listed above. |
| Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 21 days | A DLT was defined as any of the following events which occur during the DLT Period (first 21 days of ibrutinib treatment), except those that are clearly due to underlying disease or extraneous causes: a hematologic DLT (grade ≥3 anaemia, grade 4/febrile neutropenia, grade ≥3 thrombocytopenia), a non-hematologic DLT (including aspartate aminotransferase \[AST\] and/or alanine aminotransferase \[ALT\] \>3× upper limit of normal (ULN) and bilirubin \>2× ULN), any other non-hematologic toxicities ≥ Grade 3, with exceptions. |
| Phase 1: Number of Participants With Dose Interruptions | Up to a maximum of 686 days | — |
| Phase 1: Number of Participants With Dose Reductions | Up to a maximum of 686 days | — |
| Phase 2: Complete Response Rate (CRR) | Up to approximately 38 months | CRR according to the 2014 Lugano classifications determined by Independent Review Committee (IRC). CRR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles) | Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199). |
| Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles) | Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199) |
| Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles) | Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199) |
| Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles) | Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199) |
| Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles) | Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199). |
| Phase 1: Overall Response Rate (ORR) | Up to approximately 38 months | ORR according to the 2014 Lugano classification, defined as the percentage of participants with a BOR of CR or partial response (PR). |
| Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time | Up to a maximum of 711 days | Detection of ADAs was performed by using a screening assay for identification of antibody positive samples/participants, a confirmation assay, and titer assessment. |
| Phase 2: ORR | Up to approximately 38 months | ORR according to the 2014 Lugano classification, defined as the percentage of participants with a BOR of CR or PR. |
| Phase 2: CRR in Non-GCB DLBCL, GCB DLBCL, All DLBCL and MCL Participants | Up to approximately 38 months | CRR according to the 2014 Lugano classifications determined by the IRC. CRR was defined as the percentage of participants with a BOR of CR in non-GCB DLBCL, GCB DLBCL, all DLBCL, and MCL participants. |
| Phase 2: Number of Participants With TEAEs | Day 1 until 30 days after last dose; max duration of treatment was 711 days for Phase 2 (up to approximately 741 days total) | A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes form baseline in safety laboratory values, vital signs, ECOG performance status, and 12-lead ECGs which occurred after first dose of study drug were recorded as TEAEs. |
| Phase 2: Number of Participants With Serious TEAEs | Day 1 until 30 days after last dose; max duration of treatment was 711 days for Phase 2 (up to approximately 741 days total) | A serious TEAE was defined as any AE which occurred after the first dose of study drug that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance was not considered a serious adverse event), resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or important medical events that did not meet the preceding criteria but based on appropriate medical judgement may have jeopardized the participant or may have required medical or surgical intervention to prevent any of the outcomes listed above. |
| Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles) | Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199). |
| Phase 1 and Phase 2: Duration of Response (DOR) | Up to approximately 36 months | DOR was defined as the time from the first documentation of tumor response to disease progression or death. |
| Phase 1 and Phase 2: Relapse-Free Survival (RFS) | Up to approximately 36 months | RFS was defined as the time from the documentation of CR to disease progression or death. |
| Phase 1 and Phase 2: Progression-Free Survival (PFS) | Up to approximately 37 months | PFS was defined as the time between start of treatment and the first documentation of progression, or death. |
| Phase 1 and Phase 2: Overall Survival (OS) | Up to approximately 38 months | OS was defined as the time between the start of treatment and death from any cause. |
| Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles) | Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199). |
Countries
Belgium, France, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
136 participants were enrolled into sites in the United States, Belgium, France, Italy, and Spain.
Pre-assignment details
Participants were screened for eligibility to enroll within 28 days prior to the start of treatment.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib Participants with advanced diffuse large B-Cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) were enrolled to receive 60 µg/kg of loncastuximab tesirine via intravenous (IV) infusion once every 3 weeks (Q3W) for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. | 37 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib Participants with advanced DLBCL or MCL were enrolled to receive 75 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. | 4 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib Participants with advanced DLBCL or MCL were enrolled to receive 90 µg/kg of loncastuximab tesirine via IV infusion Q3W for 2 treatment cycles (cycle is 3 weeks for Cycles 1 and 2) with concurrent 560 mg ibrutinib orally via capsules once daily. Participants who had a response of partial response (PR) or stable disease (SD) at the 14-week assessment may have received 2 additional doses of loncastuximab tesirine given 4 weeks apart on Day 1 of Cycles 5 and 6. | 6 |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL Participants with non-germinal center B-cell (GCB) DLBCL received the recommended phase 2 dose (RP2D) of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of complete response (CR), partial response (PR), and stable disease (SD) received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10. | 49 |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL Participants with GCB DLBCL received the RP2D of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of CR, PR, and SD received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10. | 30 |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL Participants with MCL received the RP2D of 60 µg/kg loncastuximab tesirine via IV infusion with concurrent 560 mg ibrutinib orally via capsules once daily. Loncastuximab tesirine was administered on Day 1 of Cycles 1 and 2 (cycle is 3 weeks for Cycles 1 and 2, and 4 weeks for Cycles 3 onwards). Participants who had a response of CR, PR, and SD received additional doses of loncastuximab tesirine on Day 1 of Cycles 5, 6, 9 and 10. | 10 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Phase 1 | Death | 24 | 0 | 3 | 0 | 0 | 0 |
| Phase 1 | Investigator/Sponsor Decision | 12 | 2 | 1 | 0 | 0 | 0 |
| Phase 1 | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Phase 1 | Miscellaneous | 0 | 1 | 0 | 0 | 0 | 0 |
| Phase 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
| Phase 2 | Death | 0 | 0 | 0 | 28 | 14 | 3 |
| Phase 2 | Investigator/Sponsor Decision | 0 | 0 | 0 | 17 | 16 | 6 |
| Phase 2 | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 |
| Phase 2 | Miscellaneous | 0 | 0 | 0 | 3 | 0 | 0 |
| Phase 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL | Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL | Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 26 Participants | 3 Participants | 3 Participants | 36 Participants | 20 Participants | 5 Participants | 93 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 1 Participants | 3 Participants | 13 Participants | 10 Participants | 5 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 4 Participants | 6 Participants | 47 Participants | 27 Participants | 9 Participants | 130 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 4 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) White | 35 Participants | 4 Participants | 6 Participants | 43 Participants | 26 Participants | 10 Participants | 124 Participants |
| Sex: Female, Male Female | 10 Participants | 2 Participants | 2 Participants | 19 Participants | 9 Participants | 3 Participants | 45 Participants |
| Sex: Female, Male Male | 27 Participants | 2 Participants | 4 Participants | 30 Participants | 21 Participants | 7 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 24 / 37 | 0 / 4 | 3 / 6 | 28 / 49 | 14 / 30 | 3 / 10 |
| other Total, other adverse events | 37 / 37 | 4 / 4 | 6 / 6 | 48 / 49 | 30 / 30 | 10 / 10 |
| serious Total, serious adverse events | 19 / 37 | 0 / 4 | 3 / 6 | 27 / 49 | 5 / 30 | 5 / 10 |
Outcome results
Primary
Phase 1: Number of Participants With Dose Interruptions
Time frame: Up to a maximum of 686 days
Population: Measured in the safety population, which included all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose Interruptions | 1 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose Interruptions | 0 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose Interruptions | 0 Participants |
Primary
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
A DLT was defined as any of the following events which occur during the DLT Period (first 21 days of ibrutinib treatment), except those that are clearly due to underlying disease or extraneous causes: a hematologic DLT (grade ≥3 anaemia, grade 4/febrile neutropenia, grade ≥3 thrombocytopenia), a non-hematologic DLT (including aspartate aminotransferase \[AST\] and/or alanine aminotransferase \[ALT\] \>3× upper limit of normal (ULN) and bilirubin \>2× ULN), any other non-hematologic toxicities ≥ Grade 3, with exceptions.
Time frame: 21 days
Population: Measured in the safety population, which included all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 2 Participants |
Primary
Phase 1: Number of Participants With Dose Reductions
Time frame: Up to a maximum of 686 days
Population: Measured in the safety population, which included all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose Reductions | 0 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose Reductions | 0 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Dose Reductions | 0 Participants |
Primary
Phase 1: Number of Participants With Serious TEAEs
A serious TEAE was defined as any AE which occurred after the first dose of study drug that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance was not considered a serious adverse event), resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or important medical events that did not meet the preceding criteria but based on appropriate medical judgement may have jeopardized the participant or may have required medical or surgical intervention to prevent any of the outcomes listed above.
Time frame: Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total)
Population: Measured in the safety population, which included all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Serious TEAEs | 19 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Serious TEAEs | 0 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Serious TEAEs | 3 Participants |
Primary
Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes form baseline in safety laboratory values, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and 12-lead electrocardiograms (ECGs) which occurred after first dose of study drug were recorded as TEAEs.
Time frame: Day 1 until 30 days after last dose; max duration of treatment was 686 days for Phase 1 (up to approximately 716 days total)
Population: Measured in the safety population, which included all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 37 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
Primary
Phase 2: Complete Response Rate (CRR)
CRR according to the 2014 Lugano classifications determined by Independent Review Committee (IRC). CRR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR).
Time frame: Up to approximately 38 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Complete Response Rate (CRR) | 27.1 percentage of participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Complete Response Rate (CRR) | 26.7 percentage of participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Complete Response Rate (CRR) | 90.0 percentage of participants |
Secondary
Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)
Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).
Time frame: C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)
Population: Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The number of participants analzyed represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 1.43 ratio | Geometric Coefficient of Variation 24.6 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 1.39 ratio | Geometric Coefficient of Variation 23.3 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 1.15 ratio | — |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 1.36 ratio | Geometric Coefficient of Variation 33.8 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 1.47 ratio | Geometric Coefficient of Variation 48.4 |
| Unknown | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | — ratio | — |
| Unknown | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | — ratio | — |
| Unknown | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | — ratio | — |
| Unknown | Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Unconjugated cytotoxin SG3199 | — ratio | — |
Secondary
Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)
Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).
Time frame: C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)
Population: Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The number of participants analzyed represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 4766 day*ng/mL | Geometric Coefficient of Variation 47.1 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 8153 day*ng/mL | Geometric Coefficient of Variation 35.6 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 5197 day*ng/mL | Geometric Coefficient of Variation 7 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 5511 day*ng/mL | Geometric Coefficient of Variation 65.6 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 11397 day*ng/mL | Geometric Coefficient of Variation 48.8 |
Secondary
Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)
Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).
Time frame: C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)
Population: Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The number of participants analzyed represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 6785 day*ng/mL | Geometric Coefficient of Variation 55 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 11228 day*ng/mL | Geometric Coefficient of Variation 47.6 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 12419 day*ng/mL | — |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 6800 day*ng/mL | — |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 18090 day*ng/mL | Geometric Coefficient of Variation 29.6 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 9084 day*ng/mL | Geometric Coefficient of Variation 26.7 |
| Unknown | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | — day*ng/mL | — |
| Unknown | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | — day*ng/mL | — |
| Unknown | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | — day*ng/mL | — |
| Unknown | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Unconjugated cytotoxin SG3199 | — day*ng/mL | — |
Secondary
Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)
Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199)
Time frame: C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)
Population: Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The number of participants analzyed represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 3711 day*ng/mL | Geometric Coefficient of Variation 237 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 5528 day*ng/mL | Geometric Coefficient of Variation 244 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | 0.105 day*ng/mL | — |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 3200 day*ng/mL | Geometric Coefficient of Variation 530 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 4798 day*ng/mL | Geometric Coefficient of Variation 565 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Unconjugated cytotoxin SG3199 | 0.00700 day*ng/mL | Geometric Coefficient of Variation 1118314 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 8828 day*ng/mL | Geometric Coefficient of Variation 63 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 5681 day*ng/mL | Geometric Coefficient of Variation 52.4 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 8364 day*ng/mL | Geometric Coefficient of Variation 48.6 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 5899 day*ng/mL | Geometric Coefficient of Variation 34.3 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 15785 day*ng/mL | Geometric Coefficient of Variation 30 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 9877 day*ng/mL | Geometric Coefficient of Variation 56 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | 0.481 day*ng/mL | — |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 5772 day*ng/mL | Geometric Coefficient of Variation 50 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 8503 day*ng/mL | Geometric Coefficient of Variation 24.2 |
Secondary
Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)
Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199).
Time frame: C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)
Population: Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The number of participants analzyed represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 0.751 L/day | Geometric Coefficient of Variation 47.2 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 0.548 L/day | Geometric Coefficient of Variation 34.5 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 0.548 L/day | Geometric Coefficient of Variation 51.4 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 0.401 L/day | Geometric Coefficient of Variation 43.6 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 0.848 L/day | Geometric Coefficient of Variation 5 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 0.597 L/day | — |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 0.395 L/day | — |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 0.385 L/day | Geometric Coefficient of Variation 72.6 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 0.635 L/day | Geometric Coefficient of Variation 69 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 0.639 L/day | Geometric Coefficient of Variation 85.2 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 1.06 L/day | Geometric Coefficient of Variation 96.8 |
Secondary
Phase 1 and Phase 2: Duration of Response (DOR)
DOR was defined as the time from the first documentation of tumor response to disease progression or death.
Time frame: Up to approximately 36 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), who had at least one valid post-baseline disease assessment who achieved a response. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Duration of Response (DOR) | 7.49 months |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Duration of Response (DOR) | NA months |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Duration of Response (DOR) | 2.50 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL | Phase 1 and Phase 2: Duration of Response (DOR) | 8.25 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL | Phase 1 and Phase 2: Duration of Response (DOR) | 7.64 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL | Phase 1 and Phase 2: Duration of Response (DOR) | NA months |
Secondary
Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)
Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199)
Time frame: C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)
Population: Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The number of participants analzyed represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 753 ng/mL | Geometric Coefficient of Variation 52.7 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 1192 ng/mL | Geometric Coefficient of Variation 55.1 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | 0.0260 ng/mL | — |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 815 ng/mL | Geometric Coefficient of Variation 67 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 1328 ng/mL | Geometric Coefficient of Variation 65 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Unconjugated cytotoxin SG3199 | 0.0450 ng/mL | Geometric Coefficient of Variation 85.4 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 944 ng/mL | Geometric Coefficient of Variation 68.8 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 628 ng/mL | Geometric Coefficient of Variation 63.1 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 1270 ng/mL | Geometric Coefficient of Variation 29 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 872 ng/mL | Geometric Coefficient of Variation 23.8 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 1996 ng/mL | Geometric Coefficient of Variation 18.2 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 2073 ng/mL | Geometric Coefficient of Variation 23.5 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | 0.0480 ng/mL | — |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 1065 ng/mL | Geometric Coefficient of Variation 17 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 1111 ng/mL | Geometric Coefficient of Variation 7.48 |
Secondary
Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time
Detection of ADAs was performed by using a screening assay for identification of antibody positive samples/participants, a confirmation assay, and titer assessment.
Time frame: Up to a maximum of 711 days
Population: ADA-evaluable participants including all participants tested for ADAs in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time | 1 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time | 0 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time | 0 Participants |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL | Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time | 0 Participants |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL | Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time | 0 Participants |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL | Phase 1 and Phase 2: Number of Participants With Positive Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine at Any Time | 0 Participants |
Secondary
Phase 1 and Phase 2: Overall Survival (OS)
OS was defined as the time between the start of treatment and death from any cause.
Time frame: Up to approximately 38 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Overall Survival (OS) | 14.23 months |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Overall Survival (OS) | NA months |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Overall Survival (OS) | NA months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL | Phase 1 and Phase 2: Overall Survival (OS) | 8.54 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL | Phase 1 and Phase 2: Overall Survival (OS) | 16.76 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL | Phase 1 and Phase 2: Overall Survival (OS) | NA months |
Secondary
Phase 1 and Phase 2: Progression-Free Survival (PFS)
PFS was defined as the time between start of treatment and the first documentation of progression, or death.
Time frame: Up to approximately 37 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Progression-Free Survival (PFS) | 3.55 months |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Progression-Free Survival (PFS) | 3.17 months |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Progression-Free Survival (PFS) | 2.12 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL | Phase 1 and Phase 2: Progression-Free Survival (PFS) | 3.20 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL | Phase 1 and Phase 2: Progression-Free Survival (PFS) | 3.02 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL | Phase 1 and Phase 2: Progression-Free Survival (PFS) | NA months |
Secondary
Phase 1 and Phase 2: Relapse-Free Survival (RFS)
RFS was defined as the time from the documentation of CR to disease progression or death.
Time frame: Up to approximately 36 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment who achieved CR. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Relapse-Free Survival (RFS) | 7.49 months |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Relapse-Free Survival (RFS) | NA months |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Relapse-Free Survival (RFS) | 1.94 months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL | Phase 1 and Phase 2: Relapse-Free Survival (RFS) | NA months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in GCB DLBCL | Phase 1 and Phase 2: Relapse-Free Survival (RFS) | NA months |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in MCL | Phase 1 and Phase 2: Relapse-Free Survival (RFS) | NA months |
Secondary
Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199)
Blood samples were collected for analysis of PK data of loncastuximab tesirine (total antibody, PBD-conjugated antibody and unconjugated cytotoxin SG3199)
Time frame: C1D1 pre-dose, EOI, 4h PD, C1D8 168h PD, C1D15 336h PD, C2D1 pre-dose, EOI, 4h PD, C2D8 168h PD, C2D15 336h PD (3 week cycles)
Population: Measured in the PK population, which included all participants who had at least 1 pre-C1D1 and 1 post-dose valid PK assessment. The number of participants analzyed represents the number of participants with collected data. Analysis reported per dose of loncastuximab tesirine as pre-specified.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 0.0410 days | Geometric Coefficient of Variation 122 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 0.0420 days | Geometric Coefficient of Variation 125 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | 14.9 days | — |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 0.0470 days | Geometric Coefficient of Variation 223 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 0.0570 days | Geometric Coefficient of Variation 232 |
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Unconjugated cytotoxin SG3199 | 0.0220 days | Geometric Coefficient of Variation 19.9 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 0.0370 days | Geometric Coefficient of Variation 136 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 0.164 days | Geometric Coefficient of Variation 3347 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 0.0410 days | Geometric Coefficient of Variation 118 |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 0.0410 days | Geometric Coefficient of Variation 118 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: Total Antibody | 0.0280 days | Geometric Coefficient of Variation 37.8 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Total Antibody | 0.0250 days | Geometric Coefficient of Variation 21.1 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: Unconjugated cytotoxin SG3199 | 6.94 days | — |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 1: PBD-conjugated Antibody | 0.0330 days | Geometric Coefficient of Variation 108 |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) | Cycle 2: PBD-conjugated Antibody | 0.0280 days | Geometric Coefficient of Variation 37.8 |
Secondary
Phase 1: Overall Response Rate (ORR)
ORR according to the 2014 Lugano classification, defined as the percentage of participants with a BOR of CR or partial response (PR).
Time frame: Up to approximately 38 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Overall Response Rate (ORR) | 59.5 percentage of participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Overall Response Rate (ORR) | 50.0 percentage of participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 1: Overall Response Rate (ORR) | 50.0 percentage of participants |
Secondary
Phase 2: CRR in Non-GCB DLBCL, GCB DLBCL, All DLBCL and MCL Participants
CRR according to the 2014 Lugano classifications determined by the IRC. CRR was defined as the percentage of participants with a BOR of CR in non-GCB DLBCL, GCB DLBCL, all DLBCL, and MCL participants.
Time frame: Up to approximately 38 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included. As pre-specified, data are presented for non-GCB DLBCL, GCB DLBCL, all DLBCL, and MCL cohorts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: CRR in Non-GCB DLBCL, GCB DLBCL, All DLBCL and MCL Participants | 27.1 percentage of participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: CRR in Non-GCB DLBCL, GCB DLBCL, All DLBCL and MCL Participants | 26.7 percentage of participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: CRR in Non-GCB DLBCL, GCB DLBCL, All DLBCL and MCL Participants | 90.0 percentage of participants |
| Phase 2: Loncastuximab Tesirine and Ibrutinib in Non-Germinal Center B-cell (GCB) DLBCL | Phase 2: CRR in Non-GCB DLBCL, GCB DLBCL, All DLBCL and MCL Participants | 26.9 percentage of participants |
Secondary
Phase 2: Number of Participants With Serious TEAEs
A serious TEAE was defined as any AE which occurred after the first dose of study drug that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance was not considered a serious adverse event), resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or important medical events that did not meet the preceding criteria but based on appropriate medical judgement may have jeopardized the participant or may have required medical or surgical intervention to prevent any of the outcomes listed above.
Time frame: Day 1 until 30 days after last dose; max duration of treatment was 711 days for Phase 2 (up to approximately 741 days total)
Population: Measured in the safety population, which included all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Number of Participants With Serious TEAEs | 27 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Number of Participants With Serious TEAEs | 5 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Number of Participants With Serious TEAEs | 5 Participants |
Secondary
Phase 2: Number of Participants With TEAEs
A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes form baseline in safety laboratory values, vital signs, ECOG performance status, and 12-lead ECGs which occurred after first dose of study drug were recorded as TEAEs.
Time frame: Day 1 until 30 days after last dose; max duration of treatment was 711 days for Phase 2 (up to approximately 741 days total)
Population: Measured in the safety population, which included all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Number of Participants With TEAEs | 48 Participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Number of Participants With TEAEs | 30 Participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: Number of Participants With TEAEs | 10 Participants |
Secondary
Phase 2: ORR
ORR according to the 2014 Lugano classification, defined as the percentage of participants with a BOR of CR or PR.
Time frame: Up to approximately 38 months
Population: Measured in the efficacy analysis set, which included all participants who received at least 1 dose of study drug, who had valid baseline disease assessment(s), and who had at least one valid post-baseline disease assessment. Participants who did not have a post-baseline assessment due to early clinical progression or death (after receiving study drug) were also included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 60 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: ORR | 47.9 percentage of participants |
| Phase 1: 75 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: ORR | 46.7 percentage of participants |
| Phase 1: 90 µg/kg Loncastuximab Tesirine and Ibrutinib | Phase 2: ORR | 100 percentage of participants |