Clinical trial NCT04052997: Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma
Official title: A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed Hodgkin Lymphoma
Refractory Hodgkin Lymphoma
Keywords: Camidanlumab Tesirine; Relapsed or Refractory Hodgkins Lymphoma; Classical Hodgkins Lymphoma; Lymphoma
Lead sponsor: ADC Therapeutics S.A.
Sponsor class: INDUSTRY
First posted: 2019-08-12
Enrollment: 117
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to 3 years
measure: CR Rate
timeFrame: Up to 3 years
measure: Relapse-Free Survival (RFS)
timeFrame: Up to 3 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Number of Participants Who Received Hematopoietic Stem Cell Transplant (HSCT)
timeFrame: Up to 3 years
measure: Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to 3 years
measure: Number of Participants Who Experienced At Least One Serious Adverse Event (SAE)
timeFrame: Up to 3 years
measure: Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT)
timeFrame: EOT (up to 3 years)
measure: Maximum Observed Plasma Concentration (Cmax) of Camidanlumab Tesirine Total Antibody
timeFrame: 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)
measure: Cmax of Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: 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)
measure: Cmax of Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) For Camidanlumab Tesirine Total Antibody
timeFrame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: AUCtau For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: AUCtau For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) For Camidanlumab Tesirine Total Antibody
timeFrame: 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)
measure: AUClast For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: 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)
measure: AUClast For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) For Camidanlumab Tesirine Total Antibody
timeFrame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: AUCinf For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: AUCinf For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: Clearance (CL) For Camidanlumab Tesirine Total Antibody
timeFrame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: CL For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: CL For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: Clearance at Steady State (CLss) For Camidanlumab Tesirine Total Antibody
timeFrame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: CLss For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: CLss For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h)
measure: Apparent Terminal Elimination Half-Life (T1/2) For Camidanlumab Tesirine Total Antibody
timeFrame: 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)
measure: T1/2 For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: 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)
measure: T1/2 For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: 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)
measure: Volume of Distribution at Steady State (Vss) For Camidanlumab Tesirine Total Antibody
timeFrame: 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)
measure: Vss For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: 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)
measure: Vss For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: 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)
measure: Accumulation Index (AI) For Camidanlumab Tesirine Total Antibody
timeFrame: Cycle 1 and 2: day 0 to 21
measure: AI For Camidanlumab Tesirine PBD-Conjugated Antibody
timeFrame: Cycle 1 and 2: day 0 to 21
measure: AI For Camidanlumab Tesirine Unconjugated Warhead SG3199
timeFrame: Cycle 1 and 2: day 0 to 21
measure: Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Responses Post Dose
timeFrame: Up to 3 years
measure: 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)
timeFrame: Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years)
measure: Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
timeFrame: Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Health - Hematology and Blood and Marrow Transplant Clinic
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital - Atlanta
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute - Saint Matthews
state: Kentucky
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in Saint Louis
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center - New York
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Seidman Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi - Notre Dame
city: La Louvière
country: Belgium
facility: Hôpital de Jolimont
city: Yvoir
country: Belgium
facility: Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Brno
country: Czechia
facility: Fakultní Nemocnice Brno
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 10
country: Czechia
facility: Fakultní Nemocnice Královské Vinohrady
city: Créteil
country: France
facility: Hôpitaux Universitaires Henri Mondor
city: Dijon
country: France
facility: Hôpital François Mitterrand
city: Le Mans
country: France
facility: Clinique Victor Hugo Le Mans
city: Montpellier
country: France
facility: Hôpital Saint-Eloi
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre de Lutte Contre le Cancer - Centre Henri-Becquerel
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem
city: Alessandria
country: Italy
facility: Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo - Alessandria
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - IRCCS
city: Opole
country: Poland
facility: Szpital Wojewódzki w Opolu
city: Wrocław
country: Poland
facility: Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Universitario Quirónsalud Madrid
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - Hospital Clínico
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: València
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
Study officials:
References: