Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma
Conditions
Keywords
Loncastuximab Tesirine in Combination with Durvalumab
Brief summary
The purpose of this phase 1 study is to evaluate the safety and anti-tumor activity of Loncastuximab Tesirine (ADCT-402) and Durvalumab in participants with Advanced Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma
Detailed description
This is a Phase 1b, open-label, single-arm combination study with a dose escalation phase (Part 1) followed by a dose expansion phase (Part 2). The study will enroll approximately 75 participants. A standard 3+3 dose escalation design will be used for Part 1. The DLT period will be the 21 days after the first durvalumab dose. Part 2 will consist of up to 3 expansion cohorts, one for DLBCL, one for MCL, and one for FL. Each cohort will be approximately 20 participants treated at the dose determined in Part 1. The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3, 6, and 4 weeks), and a Follow-up Period (approximately every 12 week visits for up to 2 years after treatment discontinuation).
Interventions
DRUGLoncastuximab Tesirine and Durvalumab
intravenous infusion
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
NA
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 participants aged 18 years or older 2. Pathologic diagnosis of DLBCL, MCL, or FL 3. Participants must have relapsed or refractory disease and have failed or been intolerant to standard therapy 4. Participants who have received previous CD19-directed therapy must have a biopsy that shows CD19 expression after completion of the CD19-directed therapy 5. Measurable disease as defined by the 2014 Lugano Classification 6. Participants must be willing to undergo tumor biopsy 7. ECOG performance status 0-1 8. 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 ≥9.0 g/dL (5.59 mmol/L), transfusion allowed 4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and GGT ≤2.5 × the upper limit of normal (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-Gault equation 9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 3 days prior to start of study drug on C1D1 for women of childbearing potential 10. Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of study therapy. 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 study therapy
Exclusion criteria
1. Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody. 2. Previous therapy with any checkpoint inhibitor 3. Autologous stem cell transplant within 100 days prior to start of study drug (C1D1) 4. History of allogenic stem cell transplant 5. History of solid organ transplant 6. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion: 1. Participants with vitiligo or alopecia 2. Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement 3. Any chronic skin condition that does not require systemic therapy 4. Participants without active disease in the last 5 years may be included but only after consultation with the Study Physician 5. Participants with celiac disease controlled by diet alone 7. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice) 8. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV) 9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis 10. Lymphoma with active central nervous system (CNS) involvement at the time of screening, including leptomeningeal disease 11. 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) 12. Breastfeeding or pregnant 13. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure \[BP\] ≥160/100 mmHg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease 14. Radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. 15. Major surgery within 28 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. Note: Local surgery of isolated lesions for palliative intent is acceptable. 16. Use of any other experimental medication within 14 days prior to start of study drug (C1D1) 17. Planned live vaccine administration after starting study drug (C1D1) 18. 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. 19. Congenital long QT syndrome or a corrected QTcF interval of \>470 ms at screening (unless secondary to pacemaker or bundle branch block) 20. History of another primary malignancy except for: 1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product and of low potential risk for recurrence 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease 3. Adequately treated carcinoma in situ without evidence of disease 21. History of active primary immunodeficiency 21. History of active primary immunodeficiency or any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the patient inappropriate for study participation or put the participant at risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Day 1 to end of treatment (maximum treatment duration at study termination was 336 days) | — |
| Number of Participants With a Treatment-emergent Adverse Event (TEAE) | Day 1 to 30 days after the last dose of study drugs (maximum treatment duration at study termination was 336 days) | A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drugs to 30 days after the last dose of study drugs or initiation of new anti-cancer therapy (whichever occurred earlier). Evaluation of TEAEs included the number of participants with at least one: TEAE, serious TEAE and grade ≥3 TEAE as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 CTCAE grading scale: * Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. * Grade 4 = Life-threatening consequences; urgent intervention indicated. * Grade 5 = Death related to AE. Clinically significant changes from baseline for safety laboratory values, vital sign measurements and electrocardiograms (ECGs) were recorded as TEAEs. |
| Number of Participants With a Dose-limiting Toxicity | 21 days after first dose of durvalumab (Day 8 to Day 29) | DLTs were defined as specific events which occurred in the 21-day DLT evaluation period of the dose escalation part, except any events that were clearly due to underlying disease or extraneous causes. The grading and severity of events were based on the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. |
| Number of Participants With Changes From Baseline on the Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 1 to end of treatment (maximum treatment duration at study termination was 336 days) | Eastern Cooperative Oncology Group (ECOG) performance status was scored on a 6-point scale where higher scores indicate a worse outcome. ECOG scores included 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 1.5 years | PFS was defined as the time between start of treatment and the first documentation of progression, or death. Disease progression was defined as progressive metabolic disease and one of the following: * Target node progression. * An individual extranodal lesion must be abnormal with length \> 1.5cm and/or increase of length \> 50%. * New or clear progression of non-measured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement. |
| Overall Survival (OS) | Up to 1.5 years | OS was defined as the time between the start of treatment and death from any cause. |
| Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15 | Cmax of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. Cmax of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2. |
| 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 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15 | AUC0-last of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. AUC0-last of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2. |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15 | AUCinf of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. AUCinf of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2. |
| Overall Response Rate (ORR) | Up to 1.5 years | ORR according to the 2014 Lugano classification as determined by the investigator. Overall response rate was the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR was defined as achieving each of the following: * Partial metabolic response (findings indicate residual disease). * Partial remission (\>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by \>50% in length and no new lesions). |
| Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15 | CL for Cycle 2 reflects steady-state clearance. CL of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. |
| Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15 | Vss of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. |
| Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15 | AI is the ratio of drug accumulation after repeated administration compared to a single dose. AI of loncastuximab tesirine conjugated antibody and total antibody was calculated from Cycles 1 and 2. |
| Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | Cycle 1 (= 3 weeks): Day 1 pre-dose & Day 15; Cycles 2, 3, 5, 6, & 7 (Cycle 2 = 6 weeks, other cycles = 4 weeks): Day 1 pre-dose; 30 days after last dose of study drugs | Detection of ADAs were performed by using a screening assay for identification of antibody positive samples/patients, a confirmation assay, and titer assessment, and were performed using the Meso-Scale Discovery Electrochemiluminescence platform. |
| Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15 | Thalf of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. Thalf of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2. |
| Duration of Response (DOR) | Up to 1.5 years | DOR was defined as the time from the documentation of first tumor response (CR or PR) to disease progression or death. CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR was defined as achieving each of the following: * Partial metabolic response (findings indicate residual disease). * Partial remission (\>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by \>50% in length and no new lesions). |
| Complete Response Rate (CRR) | Up to 1.5 years | CRR was defined as the percentage of participants with a BOR of CR, according to the 2014 Lugano classification, as determined by the investigator. CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). |
| Relapse-free Survival (RFS) | Up to 1.5 years | RFS was defined as the time from the documentation of CR to disease progression or death. CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). Disease progression was defined as progressive metabolic disease and one of the following: * Target node progression. * An individual extranodal lesion must be abnormal with length \> 1.5cm and/or increase of length \> 50%. * New or clear progression of non-measured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement. |
Countries
Spain, United States
Participant flow
Recruitment details
13 participants were enrolled at 5 sites in the United States and 3 sites in Spain between February 2019 and October 2020.
Pre-assignment details
16 participants had signed informed consent, however 3 were considered screen failures. The remaining 13 participants were enrolled and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg Participants received loncastuximab tesirine as an intravenous (IV) infusion at a dose of 90 micrograms per kilogram (μg/kg) every 3 weeks (Q3W) on Day 1 of Cycles 1 and 2. Cycle 1 was 3 weeks long and Cycle 2 was 6 weeks long. Participants with a partial response (PR) or stable disease (SD) at Week 15 received an additional 2 doses of loncastuximab tesirine on Day 8 of Cycles 5 and 6. All cycles other than Cycles 1 and 2 were 4 weeks long. Participants also received durvalumab as an IV infusion at a dose of 1500 milligrams (mg) on Day 8 of Cycle 1 and Day 15 of Cycle 2, then on Day 1 of subsequent cycles. | 3 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg Participants received loncastuximab tesirine as an IV infusion at a dose of 120 μg/kg Q3W on Day 1 of Cycles 1 and 2. Cycle 1 was 3 weeks long and Cycle 2 was 6 weeks long. Participants with a PR or SD at Week 15 received an additional 2 doses of loncastuximab tesirine on Day 8 of Cycles 5 and 6. All cycles other than Cycles 1 and 2 were 4 weeks long. Participants also received durvalumab as an IV infusion at a dose of 1500 mg on Day 8 of Cycle 1 and Day 15 of Cycle 2, then on Day 1 of subsequent cycles. | 3 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg Participants received loncastuximab tesirine as an IV infusion at a dose of 150 μg/kg Q3W on Day 1 of Cycles 1 and 2. Cycle 1 was 3 weeks long and Cycle 2 was 6 weeks long. Participants with a PR or SD at Week 15 received an additional 2 doses of loncastuximab tesirine on Day 8 of Cycles 5 and 6. All cycles other than Cycles 1 and 2 were 4 weeks long. Participants also received durvalumab as an IV infusion at a dose of 1500 mg on Day 8 of Cycle 1 and Day 15 of Cycle 2, then on Day 1 of subsequent cycles. | 7 |
| Dose Expansion: Loncastuximab Tesirine The dose expansion phase was planned to consist of participants with diffuse large B-cell lymphoma, participants with mantle cell lymphoma and participants with follicular lymphoma.
Participants were planned to receive loncastuximab tesirine as an IV infusion at the maximum tolerated dose (MTD) determined in the dose escalation part and durvalumab as an IV infusion at a dose of 1500 mg on Day 8 of Cycle 1 and Day 15 of Cycle 2, then on Day 1 of subsequent cycles.
The study was terminated during the dose escalation part of the study and the dose expansion part was not initiated. | 0 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 5 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 15 | 74.0 years STANDARD_DEVIATION 2 | 63.0 years STANDARD_DEVIATION 16.94 | 66.2 years STANDARD_DEVIATION 14.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 3 | 0 / 7 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 7 / 7 | 0 / 0 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 1 / 7 | 0 / 0 |
Outcome results
Primary
Number of Participants With a Dose-limiting Toxicity
DLTs were defined as specific events which occurred in the 21-day DLT evaluation period of the dose escalation part, except any events that were clearly due to underlying disease or extraneous causes. The grading and severity of events were based on the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: 21 days after first dose of durvalumab (Day 8 to Day 29)
Population: Safety analysis set - All participants who received the study drug. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Dose-limiting Toxicity | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Dose-limiting Toxicity | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Dose-limiting Toxicity | 0 Participants |
Primary
Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction
Time frame: Day 1 to end of treatment (maximum treatment duration at study termination was 336 days)
Population: Safety analysis set - All participants who received the study drug. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Durvalumab: Dose Reduction | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Durvalumab: Dose Interruption | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Loncastuximab Tesirine: Dose Interruption | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Loncastuximab Tesirine: Dose Reduction | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Loncastuximab Tesirine: Dose Interruption | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Loncastuximab Tesirine: Dose Reduction | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Durvalumab: Dose Interruption | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Durvalumab: Dose Reduction | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Durvalumab: Dose Interruption | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Loncastuximab Tesirine: Dose Interruption | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Loncastuximab Tesirine: Dose Reduction | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction | Durvalumab: Dose Reduction | 0 Participants |
Primary
Number of Participants With a Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drugs to 30 days after the last dose of study drugs or initiation of new anti-cancer therapy (whichever occurred earlier). Evaluation of TEAEs included the number of participants with at least one: TEAE, serious TEAE and grade ≥3 TEAE as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 CTCAE grading scale: * Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. * Grade 4 = Life-threatening consequences; urgent intervention indicated. * Grade 5 = Death related to AE. Clinically significant changes from baseline for safety laboratory values, vital sign measurements and electrocardiograms (ECGs) were recorded as TEAEs.
Time frame: Day 1 to 30 days after the last dose of study drugs (maximum treatment duration at study termination was 336 days)
Population: Safety analysis set - All participants who received the study drug. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | Serious TEAE | 1 Participants |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | TEAE | 3 Participants |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | CTCAE Grade ≥3 TEAE | 2 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | Serious TEAE | 2 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | TEAE | 3 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | CTCAE Grade ≥3 TEAE | 2 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | TEAE | 7 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | CTCAE Grade ≥3 TEAE | 5 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With a Treatment-emergent Adverse Event (TEAE) | Serious TEAE | 1 Participants |
Primary
Number of Participants With Changes From Baseline on the Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) performance status was scored on a 6-point scale where higher scores indicate a worse outcome. ECOG scores included 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: Day 1 to end of treatment (maximum treatment duration at study termination was 336 days)
Population: Safety analysis set - All participants who received the study drug. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With Changes From Baseline on the Eastern Cooperative Oncology Group (ECOG) Performance Status | 2 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With Changes From Baseline on the Eastern Cooperative Oncology Group (ECOG) Performance Status | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With Changes From Baseline on the Eastern Cooperative Oncology Group (ECOG) Performance Status | 1 Participants |
Secondary
Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody
AI is the ratio of drug accumulation after repeated administration compared to a single dose. AI of loncastuximab tesirine conjugated antibody and total antibody was calculated from Cycles 1 and 2.
Time frame: Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15
Population: PK population - All participants with at least one pre- C1D1 and one post-dose valid assessment. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 2 - Total Antibody | 1.62 ratio | — |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 2 - Conjugated Antibody | 1.25 ratio | Geometric Coefficient of Variation 12.9 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 2 - Total Antibody | 2.87 ratio | — |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 2 - Conjugated Antibody | 1.77 ratio | Geometric Coefficient of Variation 33 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 2 - Total Antibody | 1.26 ratio | Geometric Coefficient of Variation 33.3 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 2 - Conjugated Antibody | 1.27 ratio | Geometric Coefficient of Variation 34.4 |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 1 - Total Antibody | — ratio | — |
| Unknown | Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody and Total Antibody | Cycle 1 - Conjugated Antibody | — ratio | — |
Secondary
Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
CL for Cycle 2 reflects steady-state clearance. CL of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2.
Time frame: Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15
Population: PK population - All participants with at least one pre- C1D1 and one post-dose valid assessment. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 0.720 liters per day (L/day) | — |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 0.927 liters per day (L/day) | Geometric Coefficient of Variation 50.7 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 0.319 liters per day (L/day) | Geometric Coefficient of Variation 6.31 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 0.212 liters per day (L/day) | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 0.872 liters per day (L/day) | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Total Antibody | 0.846 liters per day (L/day) | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 1.33 liters per day (L/day) | Geometric Coefficient of Variation 36.4 |
| Unknown | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - SG3199 | — liters per day (L/day) | — |
| Unknown | Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Conjugated Antibody | — liters per day (L/day) | — |
Secondary
Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Thalf of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. Thalf of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2.
Time frame: Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15
Population: PK population - All participants with at least one pre- C1D1 and one post-dose valid assessment. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 15.1 day | — |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 8.84 day | Geometric Coefficient of Variation 33.6 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 16.9 day | Geometric Coefficient of Variation 54.9 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 33.9 day | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 6.28 day | Geometric Coefficient of Variation 180 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Total Antibody | 8.13 day | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 5.93 day | Geometric Coefficient of Variation 213 |
| Unknown | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - SG3199 | — day | — |
| Unknown | Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Conjugated Antibody | — day | — |
Secondary
Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Vss of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2.
Time frame: Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15
Population: PK population - All participants with at least one pre- C1D1 and one post-dose valid assessment. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 13.7 liters (L) | — |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 11.3 liters (L) | Geometric Coefficient of Variation 94.4 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 7.36 liters (L) | Geometric Coefficient of Variation 38.7 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 8.61 liters (L) | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 5.14 liters (L) | Geometric Coefficient of Variation 171 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Total Antibody | 9.39 liters (L) | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 6.95 liters (L) | Geometric Coefficient of Variation 270 |
| Unknown | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - SG3199 | — liters (L) | — |
| Unknown | Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Conjugated Antibody | — liters (L) | — |
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
AUCinf of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. AUCinf of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2.
Time frame: Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15
Population: PK population - All participants with at least one pre- C1D1 and one post-dose valid assessment. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 7710 nanogram days per milliliter (day*ng/mL) | — |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 5461 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 64.5 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 18182 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 15.3 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 27875 nanogram days per milliliter (day*ng/mL) | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 15382 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 54 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Total Antibody | 15954 nanogram days per milliliter (day*ng/mL) | — |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 8504 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 41.4 |
| Unknown | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - SG3199 | — nanogram days per milliliter (day*ng/mL) | — |
| Unknown | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Conjugated Antibody | — nanogram days per milliliter (day*ng/mL) | — |
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
AUC0-last of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. AUC0-last of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2.
Time frame: Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15
Population: PK population - All participants with at least one pre- C1D1 and one post-dose valid assessment. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | 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 | Cycle 2 - Conjugated Antibody | 5305 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 24.9 |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | 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 | Cycle 2 - Total Antibody | 10388 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 21.1 |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | 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 | Cycle 1 - Conjugated Antibody | 4265 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 52.5 |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | 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 | Cycle 1 - Total Antibody | 7603 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 35 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | 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 | Cycle 2 - Conjugated Antibody | 5390 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 1410 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | 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 | Cycle 1 - Total Antibody | 29456 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 34.3 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | 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 | Cycle 1 - Conjugated Antibody | 17217 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 32.7 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | 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 | Cycle 2 - Total Antibody | 9122 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 1485 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | 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 | Cycle 2 - Total Antibody | 13264 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 67.9 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | 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 | Cycle 1 - Conjugated Antibody | 5763 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 253 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | 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 | Cycle 1 - Total Antibody | 3682 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 917 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | 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 | Cycle 1 - SG3199 | 0.00300 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 61.9 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | 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 | Cycle 2 - Conjugated Antibody | 7588 nanogram days per milliliter (day*ng/mL) | Geometric Coefficient of Variation 61.7 |
Secondary
Complete Response Rate (CRR)
CRR was defined as the percentage of participants with a BOR of CR, according to the 2014 Lugano classification, as determined by the investigator. CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology).
Time frame: Up to 1.5 years
Population: Efficacy analysis set - All participants who received at least one dose of study drug, had valid baseline disease assessment(s) and 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. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Complete Response Rate (CRR) | 0 percentage of participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Complete Response Rate (CRR) | 50 percentage of participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Complete Response Rate (CRR) | 0 percentage of participants |
Secondary
Duration of Response (DOR)
DOR was defined as the time from the documentation of first tumor response (CR or PR) to disease progression or death. CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR was defined as achieving each of the following: * Partial metabolic response (findings indicate residual disease). * Partial remission (\>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by \>50% in length and no new lesions).
Time frame: Up to 1.5 years
Population: Efficacy analysis set - All participants who received at least one dose of study drug, had valid baseline disease assessment(s) and 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. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Duration of Response (DOR) | NA months |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Duration of Response (DOR) | NA months |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Duration of Response (DOR) | NA months |
Secondary
Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Cmax of loncastuximab tesirine conjugated antibody and total antibody was calculated for Cycles 1 and 2. Cmax of warhead SG3199 was only calculated for Cycle 1 as data was not collected for Cycle 2.
Time frame: Cycles 1 and 2 (where Cycle 1 was 4 weeks long and Cycle 2 was 6 weeks long): Day 1 pre-dose and at 0.5 and 4 hours post-dose, Day 8 and Day 15
Population: Pharmacokinetics (PK) population - All participants with at least one pre- Cycle 1 Day 1 (C1D1) and one post-dose valid assessment. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 621 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.7 |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 1228 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.6 |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Conjugated Antibody | 540 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.4 |
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Total Antibody | 1001 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.6 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 1946 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.5 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Total Antibody | 3122 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 16.7 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Conjugated Antibody | 1683 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.6 |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 3510 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23.9 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Total Antibody | 2899 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 29.3 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Conjugated Antibody | 1980 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30.6 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - Total Antibody | 2966 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25.4 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 1 - SG3199 | 0.0350 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.5 |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 | Cycle 2 - Conjugated Antibody | 1582 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.7 |
Secondary
Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine
Detection of ADAs were performed by using a screening assay for identification of antibody positive samples/patients, a confirmation assay, and titer assessment, and were performed using the Meso-Scale Discovery Electrochemiluminescence platform.
Time frame: Cycle 1 (= 3 weeks): Day 1 pre-dose & Day 15; Cycles 2, 3, 5, 6, & 7 (Cycle 2 = 6 weeks, other cycles = 4 weeks): Day 1 pre-dose; 30 days after last dose of study drugs
Population: Safety analysis set - All participants who received the study drug. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | 0 Participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine | 0 Participants |
Secondary
Overall Response Rate (ORR)
ORR according to the 2014 Lugano classification as determined by the investigator. Overall response rate was the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR was defined as achieving each of the following: * Partial metabolic response (findings indicate residual disease). * Partial remission (\>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by \>50% in length and no new lesions).
Time frame: Up to 1.5 years
Population: Efficacy analysis set - All participants who received at least one dose of study drug, had valid baseline disease assessment(s) and 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. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Overall Response Rate (ORR) | 33.3 percentage of participants |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Overall Response Rate (ORR) | 100 percentage of participants |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Overall Response Rate (ORR) | 71.4 percentage of 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 1.5 years
Population: Efficacy analysis set - All participants who received at least one dose of study drug, had valid baseline disease assessment(s) and 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. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Overall Survival (OS) | NA months |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Overall Survival (OS) | NA months |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Overall Survival (OS) | NA months |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time between start of treatment and the first documentation of progression, or death. Disease progression was defined as progressive metabolic disease and one of the following: * Target node progression. * An individual extranodal lesion must be abnormal with length \> 1.5cm and/or increase of length \> 50%. * New or clear progression of non-measured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement.
Time frame: Up to 1.5 years
Population: Efficacy analysis set - All participants who received at least one dose of study drug, had valid baseline disease assessment(s) and 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. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Progression-free Survival (PFS) | NA months |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Progression-free Survival (PFS) | NA months |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Progression-free Survival (PFS) | NA months |
Secondary
Relapse-free Survival (RFS)
RFS was defined as the time from the documentation of CR to disease progression or death. CR was defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). Disease progression was defined as progressive metabolic disease and one of the following: * Target node progression. * An individual extranodal lesion must be abnormal with length \> 1.5cm and/or increase of length \> 50%. * New or clear progression of non-measured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement.
Time frame: Up to 1.5 years
Population: Efficacy analysis set - All participants who received at least one dose of study drug, had valid baseline disease assessment(s) and 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. The study was terminated prior to initiation of the dose expansion, so results are only presented for the dose escalation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dose Escalation: Loncastuximab Tesirine 90 μg/kg | Relapse-free Survival (RFS) | NA months |
| Dose Escalation: Loncastuximab Tesirine 120 μg/kg | Relapse-free Survival (RFS) | NA months |
| Dose Escalation: Loncastuximab Tesirine 150 μg/kg | Relapse-free Survival (RFS) | NA months |