Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

NCT02432235 | Completed Phase 1 Results

• 3 other identifiers: ADCT-301-0012015-005272-25199948
• Study Type: interventional
• Target: 133
• Locations: 2 countries
• Sites: 12

Brief Summary

This study evaluates camidanlumab tesirine in participants with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma.

Conditions

Hodgkin Lymphoma; Non-Hodgkin Lymphoma

Keywords

Camidanlumab tesirine

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  A DLT defined as any of the following, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as (different considerations for Adult T-Cell Leukemia/Lymphoma (ATLL) participants): * Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 febrile neutropenia or neutropenic infection * CTCAE Grade 4 neutropenia lasting \>7 days * CTCAE Grade 4 thrombocytopenia * CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion * CTCAE Grade 4 anemia A non-hematologic DLT is defined as: * CTCAE Grade 4 tumor lysis syndrome * CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, electrolyte imbalances lasting ≥ 48 hours despite optimal therapy; excluding all grades of alopecia) * CTCAE Grade 3 or higher hypersensitivity reaction * CTCAE Grade 2 or higher skin ulceration * CTCAE Grade 2 or higher peripheral sensory or motor neuropathy

  Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)

• Recommended Dose of Camidanlumab Tesirine for Part 2

  The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.

  Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)

• Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)

  An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

  Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])

• Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)

  A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

  Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])

Secondary Outcomes (14)

• Overall Response Rate (ORR)

  Day 1 to End of Study (a maximum of 12 months after treatment; median time on treatment was 43 days [min 1 day; max 354 days])

• Duration of Response (DoR)

  Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])

• Progression-Free Survival (PFS)

  Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])

• Overall Survival (OS)

  Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])

• Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine

  Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)

Study Arms (12)

3 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (3 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

Drug: Camidanlumab tesirine

5 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (5 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 4 cycles.

Drug: Camidanlumab tesirine

8 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (8 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Drug: Camidanlumab tesirine

13 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (13 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 15 cycles.

Drug: Camidanlumab tesirine

20 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (20 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Drug: Camidanlumab tesirine

30 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (30 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Drug: Camidanlumab tesirine

45 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (45 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Drug: Camidanlumab tesirine

60 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (60 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 8 cycles.

Drug: Camidanlumab tesirine

80 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (80 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 7 cycles.

Drug: Camidanlumab tesirine

100 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (100 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 5 cycles.

Drug: Camidanlumab tesirine

150 μg/kg

EXPERIMENTAL

Participants received an intravenous (IV) infusion of camidanlumab tesirine (150 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

Drug: Camidanlumab tesirine

300 μg/kg

EXPERIMENTAL

A single participant received by error an intravenous (IV) infusion of camidanlumab tesirine (300 μg/kg) on Day 1 of Cycle 1 (planned dose was 30 μg/kg). Dosing in the subsequent cycles was 30 μg/kg (for 2 more cycles).

Drug: Camidanlumab tesirine

Interventions

Camidanlumab tesirine DRUG

Intravenous (IV) infusion.

Also known as: ADCT-301, Cami

100 μg/kg; 13 μg/kg; 150 μg/kg; 20 μg/kg; 3 μg/kg; 30 μg/kg; 300 μg/kg; 45 μg/kg; 5 μg/kg; 60 μg/kg; 8 μg/kg; 80 μg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age 18 years or older.
• Refractory or relapsed lymphoma (per World Health Organization (WHO) Classification system)
• Pathologically confirmed relapsed or refractory lymphoma
• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
• Measurable disease, defined by the 2014 Lugano Classification Criteria and Global Response Score Grading Scales for cutaneous T-cell lymphoma (CTCL)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Absolute neutrophil count ≥1500/µL. Criterion not applicable to adult T cell leukemia/lymphoma (ATLL) patients.
• Platelet count of ≥75000/µL. Criterion not applicable to ATLL patients.
• Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
• Serum/plasma creatinine ≤1.5 mg/dL, or if the participant has a creatinine \> 1.5 mg/dL, a measured creatinine clearance must be \> 80 mL/min as calculated by the Cockcroft and Gault equation
• Serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase ≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if there is liver or bone involvement.
• Total serum/plasma bilirubin ≤1.5 times ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 times ULN)
• Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1.
• Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception.

You may not qualify if:

• Participants who have an option for any treatment with proven clinical benefit for their lymphoid malignancy at current state of disease.
• Active graft-versus-host disease.
• Autologous or allogenic transplant within the 60 days prior to Cycle 1 Day 1 (C1D1)
• Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
• Known history of positive serum human anti-drug antibody (ADA) or known allergy to any component of ADCT-301.
• History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis \[e.g., Wegener's granulomatosis\])
• History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis); other central nervous system autoimmune disease (e.g., poliomyelitis, multiple sclerosis).
• History of recent infection (within 4 weeks of C1D1) considered to be caused by one of the pathogens listed: herpes simplex virus Type 1 (HSV1), herpes simplex virus Type 2 (HSV2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68.
• Known seropositive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy. Note: testing is not mandatory to be eligible.
• If participant is at risk for having undiagnosed hepatitis C virus (HCV) (e.g., history of injection drug use), HCV testing should be considered.
• History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
• Pregnant or breastfeeding women.
• Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure \> 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
• Use of any other experimental medication(s) within 14 days or 5 half-lives, but in no case \< 14 days prior to the start of study treatment on Cycle 1, Day 1, except if approved by the Sponsor.
• Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy (including prednisone ≥ 40 mg/day or equivalent) within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor.

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (12)

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, 91010, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The University of Texas/MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Froedtert Hospital/Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Guy's and St. Thomas' Hospital NHS Trust

London, England, SE1 9RT, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, United Kingdom

Location

Churchill Hospital, Oxford University Hospitals NHS Foundation Trust

Oxford, England, OX3 7LE, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, United Kingdom

Location

Related Publications (3)

• Toukam M, Wuerthner J, Havenith K, Hamadani M, Caimi PF, Kopotsha T, Cruz HG, Boni JP. Population pharmacokinetics analysis of camidanlumab tesirine in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2023 Jan;91(1):13-24. doi: 10.1007/s00280-022-04486-4. Epub 2022 Nov 4.

  PMID: 36333464 DERIVED

• Toukam M, Boni JP, Hamadani M, Caimi PF, Cruz HG, Wuerthner J. Exposure-response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2023 Jan;91(1):1-12. doi: 10.1007/s00280-022-04487-3. Epub 2022 Nov 4.

  PMID: 36333463 DERIVED

• Hamadani M, Collins GP, Caimi PF, Samaniego F, Spira A, Davies A, Radford J, Menne T, Karnad A, Zain JM, Fields P, Havenith K, Cruz HG, He S, Boni J, Feingold J, Wuerthner J, Horwitz S. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol. 2021 Jun;8(6):e433-e445. doi: 10.1016/S2352-3026(21)00103-4.

  PMID: 34048682 DERIVED

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Calmodulin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Intracellular Calcium-Sensing Proteins; Intracellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Calcium-Binding Proteins; Carrier Proteins; Proteins

Results Point of Contact

• Title: Clinical Trials Information
• Organization: ADC Therapeutics SA

clinical.trials@adctherapeutics.com

954-903-7994

Study Officials

• Jens Wuerthner, MD, PhD

  ADC Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2015
• First Posted: May 4, 2015
• Study Start: October 5, 2015
• Primary Completion: October 24, 2019
• Study Completion: October 24, 2019
• Last Updated: July 13, 2021
• Results First Posted: July 13, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); GB (5)