Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma

ADC Therapeutics S.A.117 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

117

Conditions

Relapsed Hodgkin Lymphoma Refractory Hodgkin Lymphoma

Interventions

Camidanlumab TesirineDRUG

Intravenous Infusion

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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.

Locations (73)

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

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

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

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

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

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.

Data from ClinicalTrials.gov

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Mayo Clinic - Arizona

Scottsdale, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

UCSF Health - Hematology and Blood and Marrow Transplant Clinic

San Francisco, California, United States

Stanford University Medical Center

Stanford, California, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Northside Hospital - Atlanta

Atlanta, Georgia, United States

The University of Chicago Medicine

Chicago, Illinois, United States

Norton Cancer Institute - Saint Matthews

Louisville, Kentucky, United States

University of Minnesota

Minneapolis, Minnesota, United States

...and 63 more locations

Time frame: Up to 3 years

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

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

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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

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

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

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

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)

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)