Refractory Hodgkin Lymphoma, Relapsed Hodgkin Lymphoma
Conditions
Keywords
Camidanlumab Tesirine; Relapsed or Refractory Hodgkins Lymphoma; Classical Hodgkins Lymphoma; Lymphoma
Brief summary
The purpose of this study is to evaluate the clinical efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin Lymphoma (HL).
Detailed description
This is a phase 2, multi-center, open-label, single-arm study of efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin lymphoma. This study will enroll approximately 100 participants. Camidanlumab Tesirine (ADCT-301) is an antibody drug conjugate (ADC), composed of the human monoclonal antibody, HuMax®-TAC, which is directed against human CD25. The antibody is conjugated through a protease cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin. For each participant the study will include a screening period (of up to 28 days), a treatment period (cycles of 3 weeks), and a follow-up period (approximately every 12-week visits) for up to 3 years after treatment discontinuation. Participants may continue treatment for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first. Additionally, patients benefiting clinically at 1 year may continue treatment after a case by case review with the Sponsor.
Interventions
Intravenous Infusion
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent must be obtained prior to any procedures. 2. Male or female participant aged 18 years or older. (16 years or older at US based sites) 3. Pathologic diagnosis of classical Hodgkin lymphoma (cHL). 4. Patients with relapsed or refractory cHL, who have received at least 3 prior lines of systemic therapy (or at least 2 prior lines in HSCT ineligible patients) including brentuximab vedotin and a checkpoint inhibitor approved for cHL (e.g., nivolumab or pembrolizumab). Note 1: Receipt of HSCT to be included in the number of prior therapies needed to meet eligibility. 5. Measurable disease as defined by the 2014 Lugano Classification. 6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available). Note 1: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred. Note 2: If a sufficient amount of tissue is not available, a fresh biopsy may be taken, provided the procedure is not deemed high-risk and is clinically feasible, and provided it is approved locally. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 8. Adequate organ function as defined by Screening laboratory values within the following parameters: 1. Absolute neutrophil count (ANC) ≥ 1.0 × 103/μL (off growth factors at least 72 h). 2. Platelet count ≥ 75 × 103/μL without transfusion in the past 2 weeks. 3. ALT, AST, or GGT ≤ 2.5 × the upper limit of normal (ULN) if there is no liver involvement; ALT or AST ≤ 5 × ULN if there is liver involvement. 4. Total bilirubin ≤ 1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤ 3 × ULN with direct bilirubin ≤ 1.5 × ULN). 5. Blood creatinine ≤ 3.0 × ULN or calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault equation. Note: A laboratory assessment may be repeated a maximum of two times during the Screening Period to confirm eligibility. 9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential. 10. Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9.5 months after the last dose of Camidanlumab Tesirine. Men with female partners who are of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 6.5 months after the participants receives his last dose of Camidanlumab Tesirine.
Exclusion criteria
1. Previous treatment with Camidanlumab Tesirine. 2. Participation in another investigational interventional study. Being in follow-up of another investigational study is allowed. 3. Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a CD25 antibody. 4. Allogenic or autologous transplant within 60 days prior to start of study drug. 5. Active graft-versus-host disease (GVHD), except for non-neurologic symptoms as a manifestation of mild (≤ Grade 1) chronic GVHD. 6. Post-transplantation lymphoproliferative disorders. 7. Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary. 8. History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]) (subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled). 9. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis) or other central nervous system autoimmune disease (e.g., poliomyelitis, multiple sclerosis). 10. History of recent infection (within 4 weeks of Cycle 1, Day 1 \[C1D1\]) considered to be caused by one of the following pathogens: HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: An influenza test and a pathogendirected SARS CoV-2 test (such as polymerase chain reaction) are mandatory and must be negative before initiating study treatment (tests to be performed 3 days or less prior to dosing on C1D1; an additional 2 days are allowed in the event of logistical issues for receiving the results on time). 11. Participants known to be or having been infected with human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV), and require anti-viral therapy or prophylaxis. Note: Serology testing is mandatory for patients with unknown status. 12. History of Stevens-Johnson syndrome or toxic epidermal necrolysis. 13. Failure to recover ≤ Grade 1 (Common Terminology Criteria for Adverse Events version 4.0 \[CTCAE v4.0\]) from acute non-hematologic toxicity (except ≤ Grade 2 neuropathy or alopecia), due to previous therapy, prior to screening. 14. Hodgkin lymphoma (HL) with central nervous system involvement, including leptomeningeal disease. 15. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath). 16. Breastfeeding or pregnant. 17. Significant medical comorbidities, including uncontrolled hypertension (blood pressure \[BP\] ≥ 160/100 mmHg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 3 months prior to screening, severe uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease. 18. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drug, except shorter if approved by the Sponsor. 19. Use of any other experimental medication within 30 days prior to start of study drug. 20. Any live vaccine within 4 weeks prior to start of study drug and planned live vaccine administration after starting study drug. 21. Congenital long QT (measure between Q wave and T wave in the electrocardiogram) syndrome, or a corrected QTc interval of ≥ 480 ms, at screening (unless secondary to pacemaker or bundle branch block). 22. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participants inappropriate for study participation or put the participant at risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 3 years | ORR according to the 2014 Lugano classification as determined by central review in all-treated participants.ORR will be defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Data from the All-treated Population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AI For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 and 2: day 0 to 21 | AI is the ratio of AUC from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1. |
| Duration of Response (DOR) | Up to 3 years | DOR defined as the time from the first documentation of tumor response to disease progression or death. |
| CR Rate | Up to 3 years | CR rate defined as the number of treated participants with a best overall response (BOR) of CR. |
| Relapse-Free Survival (RFS) | Up to 3 years | RFS defined as the time from the documentation of CR to disease progression or death. |
| Progression-Free Survival (PFS) | Up to 3 years | PFS defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause. |
| Overall Survival (OS) | Up to 3 years | OS defined as the time from first dose of study drug until death due to any cause. |
| Number of Participants Who Received Hematopoietic Stem Cell Transplant (HSCT) | Up to 3 years | Participants receiving HSCT following camidanlumab tesirine, and without any other anticancer therapy in between, other than the therapies preparing for HSCT, were included in this analysis. |
| Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE) | Up to 3 years | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation where participants are administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy/procedure, whichever comes earlier. Clinically significant changes in vital signs, clinical laboratory results, and electrocardiogram were reported as AEs. |
| Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Responses Post Dose | Up to 3 years | Detection of ADAs was performed by using a screening assay for identification of antibody positive samples/participants, a confirmation assay, and titer assessment. |
| Number of Participants Who Experienced At Least One Serious Adverse Event (SAE) | Up to 3 years | An SAE is defined as any adverse event (AE) that: * results in death. * is life threatening. * requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE). * results in persistent or significant disability/incapacity. * is a congenital anomaly/birth defect. * important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above. Clinically significant changes in vital signs, clinical laboratory results, and electrocardiogram were reported as AEs. |
| Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT) | EOT (up to 3 years) | The ECOG Performance Status is a scale used to asses a person's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability. The scale consists of 6 grades, ranging from 0 to 5. A grade of 0 indicates the person is fully active and able to carry on as normal, and a grade of 5 indicates death. |
| Maximum Observed Plasma Concentration (Cmax) of Camidanlumab Tesirine Total Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Cmax of Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Cmax of Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Area Under the Plasma Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) For Camidanlumab Tesirine Total Antibody | Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| AUCtau For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| AUCtau For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | No data collected for this endpoint. |
| Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) For Camidanlumab Tesirine Total Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| AUClast For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| AI For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 and 2: day 0 to 21 | AI is the ratio of AUC from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1. |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) For Camidanlumab Tesirine Total Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| AUCinf For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| AUCinf For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Clearance (CL) For Camidanlumab Tesirine Total Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| CL For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| CL For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Clearance at Steady State (CLss) For Camidanlumab Tesirine Total Antibody | Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| CLss For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| CLss For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Apparent Terminal Elimination Half-Life (T1/2) For Camidanlumab Tesirine Total Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| T1/2 For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| T1/2 For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Volume of Distribution at Steady State (Vss) For Camidanlumab Tesirine Total Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Vss For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Vss For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
| Accumulation Index (AI) For Camidanlumab Tesirine Total Antibody | Cycle 1 and 2: day 0 to 21 | 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. |
| Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years) | Participants were asked to indicate their health state on a VAS with scores ranging from 'the worst health you can imagine' (score 0) to 'the best health you can imagine' (score 100). Participants are asked to mark an X on the VAS to indicate their own health and then to report the score in a text box. Positive changes from Baseline represent an an improvement in heath. |
| Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years) | The FACT-Lym consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General \[FACT-G\]) and a 15-item disease-specific questionnaire (Lymphoma Subscale). The FACT-G includes 4 domains: physical well-being, social/family well-being, emotional well-being, and functional well-being. The total FACT-Lym score (0-168) was obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life. Change was calculated as the value at the last observation minus the value at baseline. |
| AUClast For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h) | — |
Countries
Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled from September 2019 to January 2023 across 9 countries (USA, Canada, Belgium, Czech Republic, France, Hungary, Italy, Spain, UK).
Pre-assignment details
Participants with relapsed or refractory Hodgkin Lymphoma received intravenous (IV) infusions of camidanlumab tesirine.
Participants by arm
| Arm | Count |
|---|---|
| Camidanlumab Tesirine Participants received IV infusions of camidanlumab tesirine Q3W at a dose of 45 µg/kg on Day 1 of each cycle (one cycle = 21 days) for 2 cycles, followed by 30 µg/kg for subsequent cycles. | 117 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 43 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Physician Decision | 50 |
| Overall Study | Progression of Disease | 1 |
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Camidanlumab Tesirine |
|---|---|
| Age, Continuous | 42.5 Years STANDARD_DEVIATION 16.24 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score ECOG Score 0 | 64 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score ECOG Score 1 | 47 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score ECOG Score 2 | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score ECOG Score 3 | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized Missing | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 101 Participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 43 / 117 |
| other Total, other adverse events | 116 / 117 |
| serious Total, serious adverse events | 46 / 117 |
Outcome results
Primary
Overall Response Rate (ORR)
ORR according to the 2014 Lugano classification as determined by central review in all-treated participants.ORR will be defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Data from the All-treated Population.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camidanlumab Tesirine | Overall Response Rate (ORR) | 82 Participants |
Secondary
Accumulation Index (AI) For Camidanlumab Tesirine Total Antibody
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.
Time frame: Cycle 1 and 2: day 0 to 21
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | Accumulation Index (AI) For Camidanlumab Tesirine Total Antibody | 1.30 ratio | Geometric Coefficient of Variation 52.9 |
Secondary
AI For Camidanlumab Tesirine PBD-Conjugated Antibody
AI is the ratio of AUC from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1.
Time frame: Cycle 1 and 2: day 0 to 21
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | AI For Camidanlumab Tesirine PBD-Conjugated Antibody | 1.04 ratio | Geometric Coefficient of Variation 4 |
Secondary
AI For Camidanlumab Tesirine Unconjugated Warhead SG3199
AI is the ratio of AUC from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1.
Time frame: Cycle 1 and 2: day 0 to 21
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Camidanlumab Tesirine | AI For Camidanlumab Tesirine Unconjugated Warhead SG3199 | NA ratio |
Secondary
Apparent Terminal Elimination Half-Life (T1/2) For Camidanlumab Tesirine Total Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Apparent Terminal Elimination Half-Life (T1/2) For Camidanlumab Tesirine Total Antibody | Cycle 1 | 5.91 day | Geometric Coefficient of Variation 68.6 |
| Camidanlumab Tesirine | Apparent Terminal Elimination Half-Life (T1/2) For Camidanlumab Tesirine Total Antibody | Cycle 2 | 4.46 day | Geometric Coefficient of Variation 24.6 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) For Camidanlumab Tesirine Total Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) For Camidanlumab Tesirine Total Antibody | 6473 day*µg/L | Geometric Coefficient of Variation 11.9 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) For Camidanlumab Tesirine Total Antibody
Time frame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | Area Under the Plasma Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) For Camidanlumab Tesirine Total Antibody | 4037 day*ug/L | Geometric Coefficient of Variation 73.2 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) For Camidanlumab Tesirine Total Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) For Camidanlumab Tesirine Total Antibody | Cycle 1 | 489 day*ug/L | Geometric Coefficient of Variation 788 |
| Camidanlumab Tesirine | Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) For Camidanlumab Tesirine Total Antibody | Cycle 2 | 725 day*ug/L | Geometric Coefficient of Variation 897 |
Secondary
AUCinf For Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | AUCinf For Camidanlumab Tesirine PBD-Conjugated Antibody | 5478 day*µg/L | Geometric Coefficient of Variation 31.2 |
Secondary
AUCinf For Camidanlumab Tesirine Unconjugated Warhead SG3199
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Camidanlumab Tesirine | AUCinf For Camidanlumab Tesirine Unconjugated Warhead SG3199 | NA day*µg/L |
Secondary
AUClast For Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | AUClast For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 | 345 day*ug/L | Geometric Coefficient of Variation 607 |
| Camidanlumab Tesirine | AUClast For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 2 | 497 day*ug/L | Geometric Coefficient of Variation 824 |
Secondary
AUClast For Camidanlumab Tesirine Unconjugated Warhead SG3199
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | AUClast For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 | 0 day*ug/L | Geometric Coefficient of Variation 104 |
| Camidanlumab Tesirine | AUClast For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 2 | 0 day*ug/L | Geometric Coefficient of Variation 211 |
Secondary
AUCtau For Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | AUCtau For Camidanlumab Tesirine PBD-Conjugated Antibody | 3067 day*ug/L | Geometric Coefficient of Variation 65.8 |
Secondary
AUCtau For Camidanlumab Tesirine Unconjugated Warhead SG3199
No data collected for this endpoint.
Time frame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: No data collected for this endpoint.
Secondary
Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)
Participants were asked to indicate their health state on a VAS with scores ranging from 'the worst health you can imagine' (score 0) to 'the best health you can imagine' (score 100). Participants are asked to mark an X on the VAS to indicate their own health and then to report the score in a text box. Positive changes from Baseline represent an an improvement in heath.
Time frame: Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years)
Population: Patient Reported Outcome (PRO) Population: All participants in the all-treated population with baseline score (at least one instrument) and at least 1 post-baseline score (in at least one instrument).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 11 | -0.6 score on a scale | Standard Deviation 10.44 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 2 | 3.6 score on a scale | Standard Deviation 14.41 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 3 | 5.2 score on a scale | Standard Deviation 15.14 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 4 | 4.9 score on a scale | Standard Deviation 17.65 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 5 | 4.6 score on a scale | Standard Deviation 19.66 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 6 | -1.2 score on a scale | Standard Deviation 14.97 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 7 | 4.5 score on a scale | Standard Deviation 11.88 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 8 | 4.5 score on a scale | Standard Deviation 13.24 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 9 | 3.3 score on a scale | Standard Deviation 13.74 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 10 | 1.3 score on a scale | Standard Deviation 7.3 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 12 | -4.8 score on a scale | Standard Deviation 5.31 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 13 | -1.7 score on a scale | Standard Deviation 2.89 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 14 | -1.7 score on a scale | Standard Deviation 10.41 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Cycle 15 | -3.3 score on a scale | Standard Deviation 7.64 |
| Camidanlumab Tesirine | Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | EOT | -3.1 score on a scale | Standard Deviation 20.06 |
Secondary
Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
The FACT-Lym consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General \[FACT-G\]) and a 15-item disease-specific questionnaire (Lymphoma Subscale). The FACT-G includes 4 domains: physical well-being, social/family well-being, emotional well-being, and functional well-being. The total FACT-Lym score (0-168) was obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life. Change was calculated as the value at the last observation minus the value at baseline.
Time frame: Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years)
Population: PRO Population: All participants in the all-treated population with baseline score (at least one instrument) and at least 1 post-baseline score (in at least one instrument).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 2 | -0.45 score on a scale | Standard Deviation 4.079 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 3 | -0.02 score on a scale | Standard Deviation 4.935 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 4 | -0.20 score on a scale | Standard Deviation 5.384 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 5 | -0.13 score on a scale | Standard Deviation 4.906 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 6 | -1.29 score on a scale | Standard Deviation 4.318 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 7 | 0.39 score on a scale | Standard Deviation 3.892 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 8 | 0.40 score on a scale | Standard Deviation 4.419 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 9 | -1.38 score on a scale | Standard Deviation 6.262 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 10 | 1.16 score on a scale | Standard Deviation 2.374 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 11 | 1.50 score on a scale | Standard Deviation 5.167 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 12 | -1.40 score on a scale | Standard Deviation 0.548 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 13 | 0.00 score on a scale | Standard Deviation 0 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 14 | 0.00 score on a scale | Standard Deviation 0 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Cycle 15 | 0.00 score on a scale | Standard Deviation 0 |
| Camidanlumab Tesirine | Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | EOT | -3.06 score on a scale | Standard Deviation 6.802 |
Secondary
Clearance at Steady State (CLss) For Camidanlumab Tesirine Total Antibody
Time frame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | Clearance at Steady State (CLss) For Camidanlumab Tesirine Total Antibody | 0.874 L/day | Geometric Coefficient of Variation 75.6 |
Secondary
Clearance (CL) For Camidanlumab Tesirine Total Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | Clearance (CL) For Camidanlumab Tesirine Total Antibody | 0.556 L/day | Geometric Coefficient of Variation 47.9 |
Secondary
CL For Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | CL For Camidanlumab Tesirine PBD-Conjugated Antibody | 0.733 L/day | Geometric Coefficient of Variation 34.7 |
Secondary
CL For Camidanlumab Tesirine Unconjugated Warhead SG3199
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Camidanlumab Tesirine | CL For Camidanlumab Tesirine Unconjugated Warhead SG3199 | NA L/day |
Secondary
CLss For Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Camidanlumab Tesirine | CLss For Camidanlumab Tesirine PBD-Conjugated Antibody | 0.958 L/day | Geometric Coefficient of Variation 64.1 |
Secondary
CLss For Camidanlumab Tesirine Unconjugated Warhead SG3199
Time frame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Camidanlumab Tesirine | CLss For Camidanlumab Tesirine Unconjugated Warhead SG3199 | NA L/day |
Secondary
Cmax of Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Cmax of Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 | 696 µg/L | Geometric Coefficient of Variation 66.5 |
| Camidanlumab Tesirine | Cmax of Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 2 | 685 µg/L | Geometric Coefficient of Variation 61.7 |
Secondary
Cmax of Camidanlumab Tesirine Unconjugated Warhead SG3199
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Cmax of Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 | 0.0170 µg/L | Geometric Coefficient of Variation 31.6 |
| Camidanlumab Tesirine | Cmax of Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 2 | 0.0180 µg/L | Geometric Coefficient of Variation 38.3 |
Secondary
CR Rate
CR rate defined as the number of treated participants with a best overall response (BOR) of CR.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camidanlumab Tesirine | CR Rate | 39 Participants |
Secondary
Duration of Response (DOR)
DOR defined as the time from the first documentation of tumor response to disease progression or death.
Time frame: Up to 3 years
Population: Data from participants in the All-Treated Population who achieved ether CR or PR by independent reviewer.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camidanlumab Tesirine | Duration of Response (DOR) | 13.73 Months |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Camidanlumab Tesirine Total Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Maximum Observed Plasma Concentration (Cmax) of Camidanlumab Tesirine Total Antibody | Cycle 1 | 825 µg/L | Geometric Coefficient of Variation 66.7 |
| Camidanlumab Tesirine | Maximum Observed Plasma Concentration (Cmax) of Camidanlumab Tesirine Total Antibody | Cycle 2 | 797 µg/L | Geometric Coefficient of Variation 62.3 |
Secondary
Number of Participants Who Experienced At Least One Serious Adverse Event (SAE)
An SAE is defined as any adverse event (AE) that: * results in death. * is life threatening. * requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE). * results in persistent or significant disability/incapacity. * is a congenital anomaly/birth defect. * important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above. Clinically significant changes in vital signs, clinical laboratory results, and electrocardiogram were reported as AEs.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camidanlumab Tesirine | Number of Participants Who Experienced At Least One Serious Adverse Event (SAE) | 46 Participants |
Secondary
Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation where participants are administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy/procedure, whichever comes earlier. Clinically significant changes in vital signs, clinical laboratory results, and electrocardiogram were reported as AEs.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camidanlumab Tesirine | Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE) | 116 Participants |
Secondary
Number of Participants Who Received Hematopoietic Stem Cell Transplant (HSCT)
Participants receiving HSCT following camidanlumab tesirine, and without any other anticancer therapy in between, other than the therapies preparing for HSCT, were included in this analysis.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camidanlumab Tesirine | Number of Participants Who Received Hematopoietic Stem Cell Transplant (HSCT) | 18 Participants |
Secondary
Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Responses Post Dose
Detection of ADAs was performed by using a screening assay for identification of antibody positive samples/participants, a confirmation assay, and titer assessment.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camidanlumab Tesirine | Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Responses Post Dose | 2 Participants |
Secondary
Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT)
The ECOG Performance Status is a scale used to asses a person's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability. The scale consists of 6 grades, ranging from 0 to 5. A grade of 0 indicates the person is fully active and able to carry on as normal, and a grade of 5 indicates death.
Time frame: EOT (up to 3 years)
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine and reported ECOG data at EOT. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Camidanlumab Tesirine | Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT) | Score 0 | 43 Participants |
| Camidanlumab Tesirine | Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT) | Score 1 | 37 Participants |
| Camidanlumab Tesirine | Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT) | Score 2 | 12 Participants |
| Camidanlumab Tesirine | Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT) | Score 3 | 4 Participants |
Secondary
Overall Survival (OS)
OS defined as the time from first dose of study drug until death due to any cause.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camidanlumab Tesirine | Overall Survival (OS) | NA Months |
Secondary
Progression-Free Survival (PFS)
PFS defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause.
Time frame: Up to 3 years
Population: All-Treated Population: All participants who received at least 1 dose of camidanlumab tesirine. This population was used in the primary analyses of efficacy and safety.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camidanlumab Tesirine | Progression-Free Survival (PFS) | 9.13 Months |
Secondary
Relapse-Free Survival (RFS)
RFS defined as the time from the documentation of CR to disease progression or death.
Time frame: Up to 3 years
Population: Data from participants in the All-Treated Population who achieved CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camidanlumab Tesirine | Relapse-Free Survival (RFS) | 11.07 Months |
Secondary
T1/2 For Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | T1/2 For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 | 3.89 day | Geometric Coefficient of Variation 17.5 |
| Camidanlumab Tesirine | T1/2 For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 2 | 4.05 day | Geometric Coefficient of Variation 26.1 |
Secondary
T1/2 For Camidanlumab Tesirine Unconjugated Warhead SG3199
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Camidanlumab Tesirine | T1/2 For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 | NA day |
| Camidanlumab Tesirine | T1/2 For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 2 | NA day |
Secondary
Volume of Distribution at Steady State (Vss) For Camidanlumab Tesirine Total Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Volume of Distribution at Steady State (Vss) For Camidanlumab Tesirine Total Antibody | Cycle 1 | 5.91 L | Geometric Coefficient of Variation 68.6 |
| Camidanlumab Tesirine | Volume of Distribution at Steady State (Vss) For Camidanlumab Tesirine Total Antibody | Cycle 2 | 3.14 L | Geometric Coefficient of Variation 44.1 |
Secondary
Vss For Camidanlumab Tesirine PBD-Conjugated Antibody
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Camidanlumab Tesirine | Vss For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 1 | 2.81 L | Geometric Coefficient of Variation 24.9 |
| Camidanlumab Tesirine | Vss For Camidanlumab Tesirine PBD-Conjugated Antibody | Cycle 2 | 3.17 L | Geometric Coefficient of Variation 37.6 |
Secondary
Vss For Camidanlumab Tesirine Unconjugated Warhead SG3199
Time frame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
Population: PK Population: The analysis only included participants who received study drug and had at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid (measurable) assessment. Due to the nature of the studied drug (antibody-drug conjugate), some PK parameters frequently could not be measured, or could be measured only briefly.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Camidanlumab Tesirine | Vss For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 1 | NA L |
| Camidanlumab Tesirine | Vss For Camidanlumab Tesirine Unconjugated Warhead SG3199 | Cycle 2 | NA L |