Hodgkin Lymphoma, Non-Hodgkin Lymphoma
Conditions
Keywords
Camidanlumab tesirine
Brief summary
This study evaluates camidanlumab tesirine in participants with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma.
Detailed description
This is a Phase I, first in human clinical study with camidanlumab tesirine to evaluate the safety and tolerability and pharmacokinetics of camidanlumab tesirine in participants with relapsed/refractory lymphoma. Camidanlumab tesirine is a human monoclonal antibody attached via a cleavable linker to a pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells, covalently cross links deoxyribonucleic acid (DNA) preventing replication. The study will be conducted in 2 parts: Part 1 (dose escalation) and Part 2 (expansion).
Interventions
Intravenous (IV) infusion.
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 age 18 years or older. 2. Refractory or relapsed lymphoma (per World Health Organization (WHO) Classification system) 3. Pathologically confirmed relapsed or refractory lymphoma 4. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block. 5. Measurable disease, defined by the 2014 Lugano Classification Criteria and Global Response Score Grading Scales for cutaneous T-cell lymphoma (CTCL) 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 7. Absolute neutrophil count ≥1500/µL. Criterion not applicable to adult T cell leukemia/lymphoma (ATLL) patients. 8. Platelet count of ≥75000/µL. Criterion not applicable to ATLL patients. 9. Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1. 10. Serum/plasma creatinine ≤1.5 mg/dL, or if the participant has a creatinine \> 1.5 mg/dL, a measured creatinine clearance must be \> 80 mL/min as calculated by the Cockcroft and Gault equation 11. Serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase ≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if there is liver or bone involvement. 12. Total serum/plasma bilirubin ≤1.5 times ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 times ULN) 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1. 14. Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception.
Exclusion criteria
1. Participants who have an option for any treatment with proven clinical benefit for their lymphoid malignancy at current state of disease. 2. Active graft-versus-host disease. 3. Autologous or allogenic transplant within the 60 days prior to Cycle 1 Day 1 (C1D1) 4. Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy. 5. Known history of positive serum human anti-drug antibody (ADA) or known allergy to any component of ADCT-301. 6. History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]) 7. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis); other central nervous system autoimmune disease (e.g., poliomyelitis, multiple sclerosis). 8. History of recent infection (within 4 weeks of C1D1) considered to be caused by one of the pathogens listed: herpes simplex virus Type 1 (HSV1), herpes simplex virus Type 2 (HSV2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68. 9. Known seropositive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy. Note: testing is not mandatory to be eligible. If participant is at risk for having undiagnosed hepatitis C virus (HCV) (e.g., history of injection drug use), HCV testing should be considered. 10. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome. 11. Pregnant or breastfeeding women. 12. Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure \> 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias. 13. Use of any other experimental medication(s) within 14 days or 5 half-lives, but in no case \< 14 days prior to the start of study treatment on Cycle 1, Day 1, except if approved by the Sponsor. 14. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy (including prednisone ≥ 40 mg/day or equivalent) within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor. 15. Failure to recover (to Common Terminology Criteria for Adverse Events \[CTCAE Version 4.0\] Grade 0 or Grade 1) from acute non-hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening. 16. Congenital long QT syndrome or a corrected QT interval (QTc)≥ 450 ms at screening (unless secondary to pacemaker or bundle branch block). 17. Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that Sponsor Medical Monitor and Investigator agree, and document should not be exclusionary. 18. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length) | A DLT defined as any of the following, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as (different considerations for Adult T-Cell Leukemia/Lymphoma (ATLL) participants): * Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 febrile neutropenia or neutropenic infection * CTCAE Grade 4 neutropenia lasting \>7 days * CTCAE Grade 4 thrombocytopenia * CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion * CTCAE Grade 4 anemia A non-hematologic DLT is defined as: * CTCAE Grade 4 tumor lysis syndrome * CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, electrolyte imbalances lasting ≥ 48 hours despite optimal therapy; excluding all grades of alopecia) * CTCAE Grade 3 or higher hypersensitivity reaction * CTCAE Grade 2 or higher skin ulceration * CTCAE Grade 2 or higher peripheral sensory or motor neuropathy |
| Recommended Dose of Camidanlumab Tesirine for Part 2 | Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length) | The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study. |
| Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days]) | An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. |
| Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days]) | A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length) | Cmax for HuMax-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC, and free warhead (SG3199). |
| Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length) | Tmax for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). |
| Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length) | AUC0-last for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). |
| Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 2 (21 day cycle length) | AUC0-tau for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199) for Cycle 2 only. |
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 1 (21 day cycle length) | AUC∞ HuMax-TAC and PBD-conjugated HuMax-TAC for Cycle 1 only. |
| Overall Response Rate (ORR) | Day 1 to End of Study (a maximum of 12 months after treatment; median time on treatment was 43 days [min 1 day; max 354 days]) | ORR is defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with camidanlumab tesirine. Tumor response was assessed using the 2014 Lugano Classification. CR is defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR is 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 nonmeasured lesions, spleen regressed by \>50% in length and no new lesions). |
| Volume of Distribution for Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length) | Volume of distribution for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). |
| Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length) | T1/2 of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). |
| Clearance of Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length) | Clearance of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). |
| Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days]) | An assay determines the presence of anti-ADCT-301 antibodies in human serum using a validated bridging electro chemiluminescence immunoassay (ECLIA) technique. The technique uses the drug itself to capture any anti ADCT-301 antibodies present in the serum. If anti-ADCT-301 antibodies are detected, they are confirmed to be specifically against ADCT-301 and then the level of the anti-ADCT-301 antibodies present in the serum is established using a modified version of the ECLIA technique. |
| Accumulation Index (AI) for Camidanlumab Tesirine | Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length) | AI for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1 (21 day cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached. |
| Duration of Response (DoR) | Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days]) | DoR is defined among responders (complete response \[CR\] and partial response \[PR\]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification. Disease progression is defined as progressive metabolic disease and one of the follow: * 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 nonmeasured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement. DoR is presented overall for all participants who were classed as responders among the efficacy analysis set. Data is pooled for all lymphoma participants for DoR as specified in protocol section 8.4. |
| Progression-Free Survival (PFS) | Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days]) | Progression-free survival (PFS) is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is 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 nonmeasured lesions. * Regrowth of previously resolved lesions or new nodes \> 1.5 cm in length. * New or recurrent bone marrow involvement. PFS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for PFS as specified in protocol section 8.4 |
| Overall Survival (OS) | Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days]) | Overall survival (OS) is defined as the time from the first dose of study drug treatment until the date of death due to any cause. OS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for OS as specified in protocol section 8.4. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
There were 12 sites that screened and enrolled participants: USA: 7 sites; UK: 5 sites.
Pre-assignment details
Participants were included in a screening period of up to 28 days.
Participants by arm
| Arm | Count |
|---|---|
| 3 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (3 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 2 |
| 5 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (5 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 4 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 2 |
| 8 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (8 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 2 |
| 13 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (13 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 15 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 3 |
| 20 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (20 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 2 |
| 30 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (30 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 20 |
| 45 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (45 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 41 |
| 60 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (60 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 8 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 29 |
| 80 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (80 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 7 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 26 |
| 100 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (100 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 5 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 3 |
| 150 μg/kg Participants received an intravenous (IV) infusion of camidanlumab tesirine (150 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.
Camidanlumab tesirine: Intravenous (IV) infusion. | 2 |
| 300 μg/kg A single participant received by error an intravenous (IV) infusion of camidanlumab tesirine (300 μg/kg) on Day 1 of Cycle 1 (planned dose was 30 μg/kg). Dosing in the subsequent cycles was 30 μg/kg (for 2 more cycles).
Camidanlumab tesirine: Intravenous (IV) infusion. | 1 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 2 | 2 | 1 | 3 | 11 | 15 | 15 | 3 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Miscellaneous | 0 | 0 | 0 | 0 | 1 | 6 | 2 | 2 | 4 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 2 | 5 | 3 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | 300 μg/kg | 150 μg/kg | 100 μg/kg | 80 μg/kg | 60 μg/kg | 45 μg/kg | 30 μg/kg | 20 μg/kg | 13 μg/kg | 8 μg/kg | 5 μg/kg | 3 μg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 17.13 | 64.0 years | 44.5 years STANDARD_DEVIATION 19.09 | 58.7 years STANDARD_DEVIATION 8.08 | 58.1 years STANDARD_DEVIATION 15.69 | 56.3 years STANDARD_DEVIATION 18.16 | 45.1 years STANDARD_DEVIATION 15.48 | 42.1 years STANDARD_DEVIATION 16.32 | 38.0 years STANDARD_DEVIATION 19.8 | 51.0 years STANDARD_DEVIATION 12.53 | 64.0 years STANDARD_DEVIATION 12.73 | 44.0 years STANDARD_DEVIATION 2.83 | 73.5 years STANDARD_DEVIATION 2.12 |
| Body Mass Index | 27.52 kg/m^2 STANDARD_DEVIATION 7.757 | 22.14 kg/m^2 | 33.07 kg/m^2 STANDARD_DEVIATION 9.447 | 27.47 kg/m^2 STANDARD_DEVIATION 4.559 | 26.95 kg/m^2 STANDARD_DEVIATION 4.944 | 25.37 kg/m^2 STANDARD_DEVIATION 4.913 | 30.26 kg/m^2 STANDARD_DEVIATION 11.193 | 26.69 kg/m^2 STANDARD_DEVIATION 4.496 | 25.99 kg/m^2 | 21.98 kg/m^2 STANDARD_DEVIATION 2.829 | 25.83 kg/m^2 STANDARD_DEVIATION 5.1 | 22.18 kg/m^2 STANDARD_DEVIATION 5.524 | 33.60 kg/m^2 STANDARD_DEVIATION 17.816 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 43 Participants | 0 Participants | 1 Participants | 0 Participants | 7 Participants | 12 Participants | 16 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 79 Participants | 1 Participants | 1 Participants | 3 Participants | 16 Participants | 13 Participants | 24 Participants | 14 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 5 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 120 Participants | 1 Participants | 2 Participants | 3 Participants | 24 Participants | 26 Participants | 36 Participants | 18 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 171.37 centimeters (cm) STANDARD_DEVIATION 9.92 | 155.00 centimeters (cm) | 172.50 centimeters (cm) STANDARD_DEVIATION 13.435 | 173.43 centimeters (cm) STANDARD_DEVIATION 10.856 | 170.33 centimeters (cm) STANDARD_DEVIATION 10.188 | 171.43 centimeters (cm) STANDARD_DEVIATION 9.341 | 172.12 centimeters (cm) STANDARD_DEVIATION 9.41 | 172.13 centimeters (cm) STANDARD_DEVIATION 11.212 | 170.20 centimeters (cm) | 170.43 centimeters (cm) STANDARD_DEVIATION 5.811 | 176.00 centimeters (cm) STANDARD_DEVIATION 4.243 | 158.00 centimeters (cm) STANDARD_DEVIATION 1.414 | 176.65 centimeters (cm) STANDARD_DEVIATION 24.961 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 1 Participants | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 106 Participants | 1 Participants | 2 Participants | 2 Participants | 17 Participants | 28 Participants | 30 Participants | 19 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 35 participants | 0 participants | 1 participants | 1 participants | 10 participants | 9 participants | 14 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment United States | 98 participants | 1 participants | 1 participants | 2 participants | 16 participants | 20 participants | 27 participants | 20 participants | 2 participants | 3 participants | 2 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 55 Participants | 1 Participants | 1 Participants | 0 Participants | 10 Participants | 15 Participants | 14 Participants | 8 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 78 Participants | 0 Participants | 1 Participants | 3 Participants | 16 Participants | 14 Participants | 27 Participants | 12 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Weight | 80.69 kilograms (kg) STANDARD_DEVIATION 23.766 | 53.20 kilograms (kg) | 96.50 kilograms (kg) STANDARD_DEVIATION 12.869 | 82.67 kilograms (kg) STANDARD_DEVIATION 15.808 | 78.19 kilograms (kg) STANDARD_DEVIATION 15.78 | 75.15 kilograms (kg) STANDARD_DEVIATION 18.241 | 89.10 kilograms (kg) STANDARD_DEVIATION 31.926 | 79.18 kilograms (kg) STANDARD_DEVIATION 19.92 | 65.05 kilograms (kg) STANDARD_DEVIATION 14.496 | 63.57 kilograms (kg) STANDARD_DEVIATION 4.84 | 80.40 kilograms (kg) STANDARD_DEVIATION 19.658 | 55.25 kilograms (kg) STANDARD_DEVIATION 12.799 | 98.05 kilograms (kg) STANDARD_DEVIATION 26.517 |
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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 1 / 2 | 2 / 2 | 2 / 3 | 1 / 2 | 3 / 20 | 11 / 41 | 15 / 29 | 15 / 26 | 3 / 3 | 1 / 2 | 0 / 1 |
| other Total, other adverse events | 1 / 2 | 2 / 2 | 2 / 2 | 3 / 3 | 2 / 2 | 20 / 20 | 41 / 41 | 29 / 29 | 26 / 26 | 3 / 3 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 1 / 2 | 0 / 2 | 3 / 3 | 1 / 2 | 10 / 20 | 24 / 41 | 14 / 29 | 18 / 26 | 1 / 3 | 1 / 2 | 1 / 1 |
Outcome results
Primary
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Time frame: Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 1 Participants |
| 5 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| 8 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| 13 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| 20 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| 30 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 20 Participants |
| 45 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 41 Participants |
| 60 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 29 Participants |
| 80 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 26 Participants |
| 100 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| 150 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| 300 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 1 Participants |
Primary
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 0 Participants |
| 5 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| 8 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 0 Participants |
| 13 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 3 Participants |
| 20 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| 30 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 10 Participants |
| 45 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 24 Participants |
| 60 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 14 Participants |
| 80 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 18 Participants |
| 100 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| 150 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| 300 μg/kg | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT defined as any of the following, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as (different considerations for Adult T-Cell Leukemia/Lymphoma (ATLL) participants): * Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 febrile neutropenia or neutropenic infection * CTCAE Grade 4 neutropenia lasting \>7 days * CTCAE Grade 4 thrombocytopenia * CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion * CTCAE Grade 4 anemia A non-hematologic DLT is defined as: * CTCAE Grade 4 tumor lysis syndrome * CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, electrolyte imbalances lasting ≥ 48 hours despite optimal therapy; excluding all grades of alopecia) * CTCAE Grade 3 or higher hypersensitivity reaction * CTCAE Grade 2 or higher skin ulceration * CTCAE Grade 2 or higher peripheral sensory or motor neuropathy
Time frame: Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)
Population: DLT Evaluable Analysis Set: The DLT-evaluable analysis set consisted of participants who completed two cycles of ADCT-301 if enrolled prior to protocol amendment 4 and participants who completed one cycle of ADCT-301 if enrolled after protocol amendment 4. The participants with completed DLT information were included even if they discontinued early before the end of cycle 2 or cycle 1 respectively.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 5 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 8 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 13 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 20 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Participants |
| 30 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| 45 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Participants |
| 60 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 80 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Participants |
| 100 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 150 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 300 μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
Recommended Dose of Camidanlumab Tesirine for Part 2
The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.
Time frame: Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)
Population: Number of participants analyzed presented in the outcome measure data are only those participants in the DLT evaluable analysis set who were dosed at the three dose levels recommended for Part 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 μg/kg | Recommended Dose of Camidanlumab Tesirine for Part 2 | Participants with Hodgkin Lymphoma (Dose level 1: 30 µg/kg) | 30 μg/kg |
| 3 μg/kg | Recommended Dose of Camidanlumab Tesirine for Part 2 | Participants with Hodgkin Lymphoma (Dose level 2: 45 µg/kg) | 45 μg/kg |
| 3 μg/kg | Recommended Dose of Camidanlumab Tesirine for Part 2 | Participants with T-cell Lymphoma (80 µg/kg) | 80 μg/kg |
Secondary
Accumulation Index (AI) for Camidanlumab Tesirine
AI for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1 (21 day cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached.
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 8 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.00 Ratio | Geometric Coefficient of Variation 0.0000132 |
| 8 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.00 Ratio | — |
| 13 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.00 Ratio | Geometric Coefficient of Variation 0.00153 |
| 13 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.00 Ratio | Geometric Coefficient of Variation 0.000584 |
| 20 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.00 Ratio | — |
| 20 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.00 Ratio | — |
| 30 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.00 Ratio | Geometric Coefficient of Variation 0.234 |
| 30 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.01 Ratio | Geometric Coefficient of Variation 3.41 |
| 45 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.01 Ratio | Geometric Coefficient of Variation 1.48 |
| 45 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.02 Ratio | Geometric Coefficient of Variation 2.59 |
| 60 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.03 Ratio | Geometric Coefficient of Variation 4.24 |
| 60 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.03 Ratio | Geometric Coefficient of Variation 4.94 |
| 80 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.03 Ratio | Geometric Coefficient of Variation 2.38 |
| 80 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.04 Ratio | Geometric Coefficient of Variation 3.48 |
| 100 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.23 Ratio | — |
| 100 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.06 Ratio | Geometric Coefficient of Variation 8.36 |
| 150 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | Free warhead (SG3199) | 1.00 Ratio | — |
| 150 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.08 Ratio | Geometric Coefficient of Variation 6.58 |
| 150 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.06 Ratio | Geometric Coefficient of Variation 0.381 |
| 300 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | PBD-conjugated HuMax-TAC | 1.00 Ratio | — |
| 300 μg/kg | Accumulation Index (AI) for Camidanlumab Tesirine | HuMax-TAC | 1.00 Ratio | — |
Secondary
Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine
T1/2 of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 8 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.30 Days | — |
| 8 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.835 Days | Geometric Coefficient of Variation 16.9 |
| 13 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.63 Days | Geometric Coefficient of Variation 0.507 |
| 13 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.37 Days | Geometric Coefficient of Variation 5.69 |
| 20 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2.24 Days | — |
| 20 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 2.61 Days | — |
| 20 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.75 Days | — |
| 30 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.39 Days | Geometric Coefficient of Variation 49.8 |
| 30 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.78 Days | Geometric Coefficient of Variation 28.4 |
| 30 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.87 Days | Geometric Coefficient of Variation 50.7 |
| 30 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.58 Days | Geometric Coefficient of Variation 58.9 |
| 45 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 2.62 Days | Geometric Coefficient of Variation 44.1 |
| 45 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3.26 Days | Geometric Coefficient of Variation 38 |
| 45 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2.31 Days | Geometric Coefficient of Variation 45.5 |
| 45 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2.69 Days | Geometric Coefficient of Variation 40.2 |
| 60 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2.93 Days | Geometric Coefficient of Variation 62.2 |
| 60 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2.43 Days | Geometric Coefficient of Variation 44.7 |
| 60 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3.26 Days | Geometric Coefficient of Variation 59.5 |
| 60 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 2.76 Days | Geometric Coefficient of Variation 51.9 |
| 80 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.98 Days | Geometric Coefficient of Variation 78.1 |
| 80 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3.65 Days | Geometric Coefficient of Variation 42.4 |
| 80 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 3.06 Days | Geometric Coefficient of Variation 67.2 |
| 80 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2.11 Days | Geometric Coefficient of Variation 78.6 |
| 100 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2.92 Days | Geometric Coefficient of Variation 152 |
| 100 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 3.03 Days | Geometric Coefficient of Variation 156 |
| 100 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 8.74 Days | — |
| 100 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 2.49 Days | Geometric Coefficient of Variation 131 |
| 150 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 1.18 Days | — |
| 150 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 5.38 Days | Geometric Coefficient of Variation 34.4 |
| 150 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 5.59 Days | Geometric Coefficient of Variation 50.9 |
| 150 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 5.02 Days | Geometric Coefficient of Variation 2.26 |
| 150 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 4.42 Days | Geometric Coefficient of Variation 0.622 |
| 300 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 7.68 Days | — |
| 300 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.67 Days | — |
| 300 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 7.16 Days | — |
| 300 μg/kg | Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.43 Days | — |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine
AUC∞ HuMax-TAC and PBD-conjugated HuMax-TAC for Cycle 1 only.
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 1 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 20 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 917 day*ng/mL | — |
| 30 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1283 day*ng/mL | Geometric Coefficient of Variation 63.1 |
| 30 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1019 day*ng/mL | Geometric Coefficient of Variation 54.9 |
| 45 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1846 day*ng/mL | Geometric Coefficient of Variation 59.9 |
| 45 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 3001 day*ng/mL | Geometric Coefficient of Variation 75 |
| 60 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 3618 day*ng/mL | Geometric Coefficient of Variation 52.9 |
| 60 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2284 day*ng/mL | Geometric Coefficient of Variation 50.8 |
| 80 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 3261 day*ng/mL | Geometric Coefficient of Variation 83.9 |
| 80 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2797 day*ng/mL | Geometric Coefficient of Variation 81.7 |
| 100 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 3734 day*ng/mL | Geometric Coefficient of Variation 82.7 |
| 100 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 4972 day*ng/mL | Geometric Coefficient of Variation 116 |
| 150 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 13842 day*ng/mL | Geometric Coefficient of Variation 9.45 |
| 150 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 8730 day*ng/mL | Geometric Coefficient of Variation 5.31 |
| 300 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 20144 day*ng/mL | — |
| 300 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 33153 day*ng/mL | — |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine
AUC0-tau for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199) for Cycle 2 only.
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 8 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 195 day*ng/mL | Geometric Coefficient of Variation 22.3 |
| 8 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 185 day*ng/mL | — |
| 13 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 385 day*ng/mL | Geometric Coefficient of Variation 28.5 |
| 13 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 596 day*ng/mL | Geometric Coefficient of Variation 25.9 |
| 20 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 489 day*ng/mL | — |
| 20 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 747 day*ng/mL | — |
| 30 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 939 day*ng/mL | Geometric Coefficient of Variation 53.6 |
| 30 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1384 day*ng/mL | Geometric Coefficient of Variation 62.6 |
| 45 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2183 day*ng/mL | Geometric Coefficient of Variation 61.6 |
| 45 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3604 day*ng/mL | Geometric Coefficient of Variation 68.9 |
| 60 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2811 day*ng/mL | Geometric Coefficient of Variation 76.7 |
| 60 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 4688 day*ng/mL | Geometric Coefficient of Variation 98.3 |
| 80 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 3469 day*ng/mL | Geometric Coefficient of Variation 91.3 |
| 80 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 5689 day*ng/mL | Geometric Coefficient of Variation 58.2 |
| 100 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 18830 day*ng/mL | — |
| 100 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1809 day*ng/mL | Geometric Coefficient of Variation 4154 |
| 150 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0310 day*ng/mL | — |
| 150 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 17031 day*ng/mL | Geometric Coefficient of Variation 45.1 |
| 150 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 9851 day*ng/mL | Geometric Coefficient of Variation 28.3 |
| 300 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 763 day*ng/mL | — |
| 300 μg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1074 day*ng/mL | — |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine
AUC0-last for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 3 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 12.0 day*ng/mL | — |
| 3 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 21.0 day*ng/mL | — |
| 3 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 18.6 day*ng/mL | — |
| 3 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 82.7 day*ng/mL | — |
| 5 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 2.60 day*ng/mL | — |
| 8 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 111 day*ng/mL | Geometric Coefficient of Variation 35 |
| 8 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 48.2 day*ng/mL | Geometric Coefficient of Variation 207 |
| 8 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 58.8 day*ng/mL | Geometric Coefficient of Variation 458 |
| 8 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 85.8 day*ng/mL | Geometric Coefficient of Variation 15.9 |
| 13 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 453 day*ng/mL | Geometric Coefficient of Variation 35.3 |
| 13 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 237 day*ng/mL | Geometric Coefficient of Variation 23.1 |
| 13 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 76.3 day*ng/mL | Geometric Coefficient of Variation 1444 |
| 13 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 76.8 day*ng/mL | Geometric Coefficient of Variation 470 |
| 20 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 660 day*ng/mL | Geometric Coefficient of Variation 93.7 |
| 20 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 473 day*ng/mL | — |
| 20 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 330 day*ng/mL | — |
| 20 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 262 day*ng/mL | Geometric Coefficient of Variation 276 |
| 30 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1004 day*ng/mL | Geometric Coefficient of Variation 66.8 |
| 30 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 967 day*ng/mL | Geometric Coefficient of Variation 60.4 |
| 30 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 655 day*ng/mL | Geometric Coefficient of Variation 53.3 |
| 30 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 625 day*ng/mL | Geometric Coefficient of Variation 53.1 |
| 45 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 2476 day*ng/mL | Geometric Coefficient of Variation 117 |
| 45 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.00200 day*ng/mL | Geometric Coefficient of Variation 331 |
| 45 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1715 day*ng/mL | Geometric Coefficient of Variation 128 |
| 45 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1173 day*ng/mL | Geometric Coefficient of Variation 113 |
| 45 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1514 day*ng/mL | Geometric Coefficient of Variation 103 |
| 45 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.00300 day*ng/mL | Geometric Coefficient of Variation 74.6 |
| 60 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 2491 day*ng/mL | Geometric Coefficient of Variation 132 |
| 60 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.00200 day*ng/mL | Geometric Coefficient of Variation 127 |
| 60 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2283 day*ng/mL | Geometric Coefficient of Variation 94.5 |
| 60 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1623 day*ng/mL | Geometric Coefficient of Variation 102 |
| 60 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0330 day*ng/mL | Geometric Coefficient of Variation 183 |
| 60 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3665 day*ng/mL | Geometric Coefficient of Variation 127 |
| 80 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 3038 day*ng/mL | Geometric Coefficient of Variation 97.7 |
| 80 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1630 day*ng/mL | Geometric Coefficient of Variation 155 |
| 80 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 2751 day*ng/mL | Geometric Coefficient of Variation 109 |
| 80 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.00300 day*ng/mL | Geometric Coefficient of Variation 290 |
| 80 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 4190 day*ng/mL | Geometric Coefficient of Variation 123 |
| 80 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.00600 day*ng/mL | Geometric Coefficient of Variation 79.8 |
| 100 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 4091 day*ng/mL | Geometric Coefficient of Variation 84.6 |
| 100 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 921 day*ng/mL | Geometric Coefficient of Variation 1700356 |
| 100 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2849 day*ng/mL | Geometric Coefficient of Variation 68 |
| 100 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.00300 day*ng/mL | — |
| 100 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1482 day*ng/mL | Geometric Coefficient of Variation 13082 |
| 100 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0100 day*ng/mL | — |
| 150 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 7727 day*ng/mL | Geometric Coefficient of Variation 11.2 |
| 150 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.00400 day*ng/mL | — |
| 150 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 12767 day*ng/mL | Geometric Coefficient of Variation 13.1 |
| 150 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 8992 day*ng/mL | Geometric Coefficient of Variation 28.3 |
| 150 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0130 day*ng/mL | Geometric Coefficient of Variation 5.6 |
| 150 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 12919 day*ng/mL | Geometric Coefficient of Variation 14.6 |
| 300 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 919 day*ng/mL | — |
| 300 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 30759 day*ng/mL | — |
| 300 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 18915 day*ng/mL | — |
| 300 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 634 day*ng/mL | — |
| 300 μg/kg | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0360 day*ng/mL | — |
Secondary
Clearance of Camidanlumab Tesirine
Clearance of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 8 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 3.27 Liters/day | — |
| 8 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3.23 Liters/day | Geometric Coefficient of Variation 50.1 |
| 13 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.44 Liters/day | Geometric Coefficient of Variation 22.5 |
| 13 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.79 Liters/day | Geometric Coefficient of Variation 25.1 |
| 20 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 2.01 Liters/day | — |
| 20 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2.46 Liters/day | — |
| 20 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.943 Liters/day | — |
| 30 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.93 Liters/day | Geometric Coefficient of Variation 57.2 |
| 30 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.60 Liters/day | Geometric Coefficient of Variation 66.5 |
| 30 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.82 Liters/day | Geometric Coefficient of Variation 69 |
| 30 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.75 Liters/day | Geometric Coefficient of Variation 55.6 |
| 45 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.37 Liters/day | Geometric Coefficient of Variation 55.3 |
| 45 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.29 Liters/day | Geometric Coefficient of Variation 64 |
| 45 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.03 Liters/day | Geometric Coefficient of Variation 61.2 |
| 45 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.68 Liters/day | Geometric Coefficient of Variation 50.3 |
| 60 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.24 Liters/day | Geometric Coefficient of Variation 54.5 |
| 60 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.950 Liters/day | Geometric Coefficient of Variation 85.9 |
| 60 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.65 Liters/day | Geometric Coefficient of Variation 48.9 |
| 60 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.27 Liters/day | Geometric Coefficient of Variation 62.8 |
| 80 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.87 Liters/day | Geometric Coefficient of Variation 99 |
| 80 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.60 Liters/day | Geometric Coefficient of Variation 184 |
| 80 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.10 Liters/day | Geometric Coefficient of Variation 46.2 |
| 80 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.44 Liters/day | Geometric Coefficient of Variation 86.9 |
| 100 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.82 Liters/day | Geometric Coefficient of Variation 136 |
| 100 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.94 Liters/day | Geometric Coefficient of Variation 98.7 |
| 100 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 3.28 Liters/day | Geometric Coefficient of Variation 2602 |
| 100 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.446 Liters/day | — |
| 150 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.849 Liters/day | Geometric Coefficient of Variation 30.8 |
| 150 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1.05 Liters/day | Geometric Coefficient of Variation 22.6 |
| 150 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1.33 Liters/day | Geometric Coefficient of Variation 18.4 |
| 150 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 4302 Liters/day | — |
| 150 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.17 Liters/day | Geometric Coefficient of Variation 15 |
| 300 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.489 Liters/day | — |
| 300 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1.23 Liters/day | — |
| 300 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.643 Liters/day | — |
| 300 μg/kg | Clearance of Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1.38 Liters/day | — |
Secondary
Duration of Response (DoR)
DoR is defined among responders (complete response \[CR\] and partial response \[PR\]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification. Disease progression is defined as progressive metabolic disease and one of the follow: * 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 nonmeasured lesions. * Regrowth of previously resolved lesions or new nodes \>1.5 cm in length. * New or recurrent bone marrow involvement. DoR is presented overall for all participants who were classed as responders among the efficacy analysis set. Data is pooled for all lymphoma participants for DoR as specified in protocol section 8.4.
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Population: Efficacy Analysis Set: The efficacy analysis set consisted of participants who received at least one dose of camidanlumab tesirine with a valid baseline and at least one valid post-baseline disease assessment or participants who had documented progression of disease or death at any time after the first dose of study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 3 μg/kg | Duration of Response (DoR) | 5.19 Months |
Secondary
Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine
Cmax for HuMax-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC, and free warhead (SG3199).
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 3 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 67.5 ng/mL | — |
| 3 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 61.5 ng/mL | — |
| 3 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 109 ng/mL | — |
| 3 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 79.5 ng/mL | — |
| 5 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 62.5 ng/mL | — |
| 8 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 177 ng/mL | Geometric Coefficient of Variation 39.4 |
| 8 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 131 ng/mL | Geometric Coefficient of Variation 20.7 |
| 8 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 151 ng/mL | Geometric Coefficient of Variation 23.2 |
| 8 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 127 ng/mL | Geometric Coefficient of Variation 27.6 |
| 13 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 152 ng/mL | Geometric Coefficient of Variation 95.1 |
| 13 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 189 ng/mL | Geometric Coefficient of Variation 98.4 |
| 13 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 208 ng/mL | Geometric Coefficient of Variation 18.4 |
| 13 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 254 ng/mL | Geometric Coefficient of Variation 13.1 |
| 20 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 224 ng/mL | — |
| 20 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 318 ng/mL | Geometric Coefficient of Variation 82.9 |
| 20 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 241 ng/mL | Geometric Coefficient of Variation 76.7 |
| 20 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 164 ng/mL | — |
| 30 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 603 ng/mL | Geometric Coefficient of Variation 31.8 |
| 30 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 554 ng/mL | Geometric Coefficient of Variation 48.1 |
| 30 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 424 ng/mL | Geometric Coefficient of Variation 47.8 |
| 30 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 455 ng/mL | Geometric Coefficient of Variation 38.5 |
| 45 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 648 ng/mL | Geometric Coefficient of Variation 51 |
| 45 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 803 ng/mL | Geometric Coefficient of Variation 54.4 |
| 45 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1040 ng/mL | Geometric Coefficient of Variation 60 |
| 45 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 808 ng/mL | Geometric Coefficient of Variation 55.8 |
| 45 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0120 ng/mL | Geometric Coefficient of Variation 8.04 |
| 45 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0170 ng/mL | Geometric Coefficient of Variation 46.9 |
| 60 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1084 ng/mL | Geometric Coefficient of Variation 59.9 |
| 60 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1120 ng/mL | Geometric Coefficient of Variation 82.8 |
| 60 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 881 ng/mL | Geometric Coefficient of Variation 78.8 |
| 60 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1402 ng/mL | Geometric Coefficient of Variation 56.1 |
| 60 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.132 ng/mL | Geometric Coefficient of Variation 413 |
| 60 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0310 ng/mL | Geometric Coefficient of Variation 102 |
| 80 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 1379 ng/mL | Geometric Coefficient of Variation 32.2 |
| 80 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1055 ng/mL | Geometric Coefficient of Variation 45.9 |
| 80 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1325 ng/mL | Geometric Coefficient of Variation 43.1 |
| 80 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0140 ng/mL | Geometric Coefficient of Variation 4.21 |
| 80 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 1084 ng/mL | Geometric Coefficient of Variation 32 |
| 80 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0150 ng/mL | Geometric Coefficient of Variation 34.6 |
| 100 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 645 ng/mL | Geometric Coefficient of Variation 655 |
| 100 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 1494 ng/mL | Geometric Coefficient of Variation 26.1 |
| 100 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 1154 ng/mL | Geometric Coefficient of Variation 26.4 |
| 100 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0270 ng/mL | — |
| 100 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 800 ng/mL | Geometric Coefficient of Variation 726 |
| 100 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0110 ng/mL | — |
| 150 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0170 ng/mL | Geometric Coefficient of Variation 20.1 |
| 150 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 2671 ng/mL | Geometric Coefficient of Variation 32.9 |
| 150 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2097 ng/mL | Geometric Coefficient of Variation 21.1 |
| 150 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0170 ng/mL | — |
| 150 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2090 ng/mL | Geometric Coefficient of Variation 31.6 |
| 150 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3251 ng/mL | Geometric Coefficient of Variation 37.8 |
| 300 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 5020 ng/mL | — |
| 300 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 4020 ng/mL | — |
| 300 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 497 ng/mL | — |
| 300 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.0240 ng/mL | — |
| 300 μg/kg | Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 497 ng/mL | — |
Secondary
Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine
An assay determines the presence of anti-ADCT-301 antibodies in human serum using a validated bridging electro chemiluminescence immunoassay (ECLIA) technique. The technique uses the drug itself to capture any anti ADCT-301 antibodies present in the serum. If anti-ADCT-301 antibodies are detected, they are confirmed to be specifically against ADCT-301 and then the level of the anti-ADCT-301 antibodies present in the serum is established using a modified version of the ECLIA technique.
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Population: Safety Analysis Set - The safety analysis set consisted of all participants who received camidanlumab tesirine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 3 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 3 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 3 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 5 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 5 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 5 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 8 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 8 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 8 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 13 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 13 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 13 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 20 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 20 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 20 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 30 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 30 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 30 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 45 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 45 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 45 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 60 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 60 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 60 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 80 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 80 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 80 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 100 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 100 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 100 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 150 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 150 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 150 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
| 300 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA pre-dose | 0 Participants |
| 300 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA post-dose only | 0 Participants |
| 300 μg/kg | Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine | Confirmed positive ADA at any time | 0 Participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with camidanlumab tesirine. Tumor response was assessed using the 2014 Lugano Classification. CR is defined as achieving each of the following: * Complete metabolic response. * Complete radiologic response (target node regress to \<1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR is 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 nonmeasured lesions, spleen regressed by \>50% in length and no new lesions).
Time frame: Day 1 to End of Study (a maximum of 12 months after treatment; median time on treatment was 43 days [min 1 day; max 354 days])
Population: Efficacy Analysis Set: The efficacy analysis set consisted of participants who received at least one dose of camidanlumab tesirine with a valid baseline and at least one valid post-baseline disease assessment or participants who had documented progression of disease or death at any time after the first dose of study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3 μg/kg | Overall Response Rate (ORR) | 0 Participants |
| 5 μg/kg | Overall Response Rate (ORR) | 0 Participants |
| 8 μg/kg | Overall Response Rate (ORR) | 0 Participants |
| 13 μg/kg | Overall Response Rate (ORR) | 1 Participants |
| 20 μg/kg | Overall Response Rate (ORR) | 0 Participants |
| 30 μg/kg | Overall Response Rate (ORR) | 11 Participants |
| 45 μg/kg | Overall Response Rate (ORR) | 32 Participants |
| 60 μg/kg | Overall Response Rate (ORR) | 15 Participants |
| 80 μg/kg | Overall Response Rate (ORR) | 12 Participants |
| 100 μg/kg | Overall Response Rate (ORR) | 2 Participants |
| 150 μg/kg | Overall Response Rate (ORR) | 1 Participants |
| 300 μg/kg | Overall Response Rate (ORR) | 1 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) is defined as the time from the first dose of study drug treatment until the date of death due to any cause. OS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for OS as specified in protocol section 8.4.
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Population: Efficacy Analysis Set: The efficacy analysis set consisted of participants who received at least one dose of camidanlumab tesirine with a valid baseline and at least one valid post-baseline disease assessment or participants who had documented progression of disease or death at any time after the first dose of study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 3 μg/kg | Overall Survival (OS) | 16.26 Months |
Secondary
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is 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 nonmeasured lesions. * Regrowth of previously resolved lesions or new nodes \> 1.5 cm in length. * New or recurrent bone marrow involvement. PFS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for PFS as specified in protocol section 8.4
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Population: Efficacy Analysis Set: The efficacy analysis set consisted of participants who received at least one dose of camidanlumab tesirine with a valid baseline and at least one valid post-baseline disease assessment or participants who had documented progression of disease or death at any time after the first dose of study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 3 μg/kg | Progression-Free Survival (PFS) | 5.22 Months |
Secondary
Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine
Tmax for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 3 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.336 Days | — |
| 3 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.155 Days | — |
| 3 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.155 Days | — |
| 3 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.149 Days | — |
| 5 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.0830 Days | — |
| 8 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.114 Days | Geometric Coefficient of Variation 46.4 |
| 8 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.126 Days | Geometric Coefficient of Variation 37.9 |
| 8 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.0970 Days | Geometric Coefficient of Variation 22.4 |
| 8 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.110 Days | Geometric Coefficient of Variation 32.2 |
| 13 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.149 Days | Geometric Coefficient of Variation 75.3 |
| 13 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0860 Days | Geometric Coefficient of Variation 1.7 |
| 13 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.110 Days | Geometric Coefficient of Variation 24.6 |
| 13 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.137 Days | Geometric Coefficient of Variation 69.8 |
| 20 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.103 Days | Geometric Coefficient of Variation 26.4 |
| 20 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0920 Days | — |
| 20 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.131 Days | Geometric Coefficient of Variation 64.3 |
| 20 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.130 Days | — |
| 30 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.0910 Days | Geometric Coefficient of Variation 47.1 |
| 30 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.0820 Days | Geometric Coefficient of Variation 38.5 |
| 30 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.0640 Days | Geometric Coefficient of Variation 105 |
| 30 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0640 Days | Geometric Coefficient of Variation 121 |
| 45 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.192 Days | Geometric Coefficient of Variation 42.6 |
| 45 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.0950 Days | Geometric Coefficient of Variation 67.5 |
| 45 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.0950 Days | Geometric Coefficient of Variation 62.4 |
| 45 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.119 Days | Geometric Coefficient of Variation 75 |
| 45 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.0790 Days | Geometric Coefficient of Variation 81.6 |
| 45 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0660 Days | Geometric Coefficient of Variation 64.3 |
| 60 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.0970 Days | Geometric Coefficient of Variation 44.6 |
| 60 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0690 Days | Geometric Coefficient of Variation 110 |
| 60 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.0970 Days | Geometric Coefficient of Variation 119 |
| 60 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.0910 Days | Geometric Coefficient of Variation 100 |
| 60 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.124 Days | Geometric Coefficient of Variation 83.6 |
| 60 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.106 Days | Geometric Coefficient of Variation 58.3 |
| 80 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.206 Days | Geometric Coefficient of Variation 69.8 |
| 80 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.0830 Days | Geometric Coefficient of Variation 71.7 |
| 80 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.105 Days | Geometric Coefficient of Variation 45.1 |
| 80 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0720 Days | Geometric Coefficient of Variation 79.3 |
| 80 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.118 Days | Geometric Coefficient of Variation 83 |
| 80 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.201 Days | Geometric Coefficient of Variation 24.8 |
| 100 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.0700 Days | Geometric Coefficient of Variation 31.4 |
| 100 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.111 Days | Geometric Coefficient of Variation 22.3 |
| 100 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.111 Days | Geometric Coefficient of Variation 22.3 |
| 100 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.167 Days | — |
| 100 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0850 Days | Geometric Coefficient of Variation 2.89 |
| 100 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.211 Days | — |
| 150 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0940 Days | Geometric Coefficient of Variation 160 |
| 150 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 0.156 Days | Geometric Coefficient of Variation 109 |
| 150 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.114 Days | Geometric Coefficient of Variation 46.7 |
| 150 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.145 Days | Geometric Coefficient of Variation 21.1 |
| 150 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.240 Days | — |
| 150 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.157 Days | Geometric Coefficient of Variation 0.937 |
| 300 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - Free warhead (SG3199) | 0.172 Days | — |
| 300 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 0.0830 Days | — |
| 300 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 0.0310 Days | — |
| 300 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 0.172 Days | — |
| 300 μg/kg | Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 0.0310 Days | — |
Secondary
Volume of Distribution for Camidanlumab Tesirine
Volume of distribution for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Population: Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 8 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3.71 Liters | Geometric Coefficient of Variation 70.3 |
| 8 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 5.89 Liters | — |
| 13 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 3.26 Liters | Geometric Coefficient of Variation 19.9 |
| 13 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 3.56 Liters | Geometric Coefficient of Variation 14.7 |
| 20 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 2.23 Liters | — |
| 20 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 8.39 Liters | — |
| 20 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 7.72 Liters | — |
| 30 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 3.28 Liters | Geometric Coefficient of Variation 56.7 |
| 30 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 4.81 Liters | Geometric Coefficient of Variation 53 |
| 30 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 3.93 Liters | Geometric Coefficient of Variation 43.2 |
| 30 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 4.28 Liters | Geometric Coefficient of Variation 60.1 |
| 45 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 5.08 Liters | Geometric Coefficient of Variation 23.3 |
| 45 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 4.57 Liters | Geometric Coefficient of Variation 26.9 |
| 45 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 4.91 Liters | Geometric Coefficient of Variation 29.9 |
| 45 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 4.54 Liters | Geometric Coefficient of Variation 36 |
| 60 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 5.05 Liters | Geometric Coefficient of Variation 25.5 |
| 60 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 4.64 Liters | Geometric Coefficient of Variation 26.5 |
| 60 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 5.10 Liters | Geometric Coefficient of Variation 30.2 |
| 60 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 4.55 Liters | Geometric Coefficient of Variation 27 |
| 80 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 4.28 Liters | Geometric Coefficient of Variation 159 |
| 80 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 5.23 Liters | Geometric Coefficient of Variation 24.8 |
| 80 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 5.15 Liters | Geometric Coefficient of Variation 34.5 |
| 80 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 5.89 Liters | Geometric Coefficient of Variation 25.7 |
| 100 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 5.55 Liters | — |
| 100 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 6.11 Liters | Geometric Coefficient of Variation 8.73 |
| 100 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 14.5 Liters | Geometric Coefficient of Variation 257 |
| 100 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 6.91 Liters | Geometric Coefficient of Variation 14.4 |
| 150 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 7.01 Liters | Geometric Coefficient of Variation 46.4 |
| 150 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 6.13 Liters | Geometric Coefficient of Variation 6.58 |
| 150 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 9.03 Liters | Geometric Coefficient of Variation 71.7 |
| 150 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - Free warhead (SG3199) | 7246 Liters | — |
| 150 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 7.55 Liters | Geometric Coefficient of Variation 8.86 |
| 300 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - HuMax-TAC | 2.44 Liters | — |
| 300 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - PBD-conjugated HuMax-TAC | 5.84 Liters | — |
| 300 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 1 - HuMax-TAC | 4.84 Liters | — |
| 300 μg/kg | Volume of Distribution for Camidanlumab Tesirine | Cycle 2 - PBD-conjugated HuMax-TAC | 2.90 Liters | — |