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Study of ADCT-301 in Patients With Selected Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03621982
Recruitment Status : Not yet recruiting
First Posted : August 9, 2018
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics S.A.

Brief Summary:
This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content Head and Neck Cancer Non-small Cell Lung Cancer Gastric Cancer Esophageal Cancer Pancreas Cancer Bladder Cancer Renal Cell Carcinoma Melanoma Triple-negative Breast Cancer Ovarian Cancer Drug: ADCT-301 Phase 1

Detailed Description:

This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a dose expansion part.

The duration of the study participation for each patient is defined as the time from the date of signed written informed consent to the completion of the follow-up period, withdrawal of consent, loss to follow-up, or death, whichever occurs first.

The study will include a Screening Period (of up to 28 days), a Treatment Period (with cycles of 3 weeks for a Q3W dosing regimen), and a Follow-up Period (approximately every 12 week visits) for up to 1 year after treatment discontinuation


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) in Patients With Selected Advanced Solid Tumors
Estimated Study Start Date : August 2, 2018
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : July 2021


Arm Intervention/treatment
Experimental: ADCT-301

In Part 1 (dose-escalation), patients will receive a 1-hour intravenous infusion of ADCT-301 on Day 1 every 3 weeks (21-day cycle). at escalating doses. Part 1 will continue until the maximum tolerated dose or the recommended dose(s) and schedule(s) for expansion are determined.

In Part 2 (expansion), patients will be assigned to receive the recommended dose(s) of ADCT-301 as determined by the Dose Escalation Steering Committee (DESC).

This study will investigate dose levels between 20 μg/kg and 300 μg/kg Q3W.

Drug: ADCT-301
intravenous infusion
Other Name: Camidanlumab tesirine




Primary Outcome Measures :
  1. Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose Dose Limiting toxicities as defined per protocol, as related to ADCT-301 [ Time Frame: The protocol-defined assessment period is one 21-day cycle ]

Secondary Outcome Measures :
  1. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days) ]
    Overall response rate (ORR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and iRECIST

  2. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days) ]
    Duration of response (DOR) defined as the time from the first documentation of tumor response to disease progression or death

  3. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days) ]
    Progression-free survival (PFS) defined as the time between start of treatment and the first documentation of recurrence, progression, or death

  4. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days) ]
    Overall survival (OS) defined as the time between the start of treatment and death from any cause

  5. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of the maximum concentration (Cmax)

  6. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of the time to maximum concentration (Tmax)

  7. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last)

  8. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞)

  9. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)

  10. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of the accumulation index (AI)

  11. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of clearance (CL)

  12. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days) ]
    Noncompartmental analysis of volume of distribution (Vd)

  13. Evaluate the immunogenicityof camidanlumab tesirine [ Time Frame: Blood sample collection on Day 1 and Day 15 for Cycle 1 and Day 1 only for Cycle 2,Cycle 3,Cycle 4 and then Day 1 of every other cycle (cycle = 21 days) ]
    Anti-drug antibody (ADA) titers in serum



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained prior to any procedures.
  2. Male or female patient aged 18 years or older.
  3. Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening:

    Part 1 (Dose-Escalation):

    Advanced solid tumors with literature evidence of CD25(+) Treg content, i.e., head and neck, non-small cell lung cancer, gastric and esophageal cancers, pancreas, bladder, renal cell carcinoma, melanoma, triple negative breast cancer, and ovarian cancers.

    Part 2 (Dose-Expansion):

    Advanced solid tumors literature evidence of CD25(+) Treg content:

    • Group 1: One of the indications identified in Part 1, for which at least 1 response (PR or CR) was seen.
    • Group 2: Any indication allowed in Part 1, except for the one selected for Group 1.
  4. Patients who are refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
  5. Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST v1.1 or irRC/irRECIST/iRECIST.
  6. Patient must have a site of disease amenable to biopsy and be willing to undergo fresh biopsy procedures (minimum 3 passes each) prior to first dose, according to the treating institution's guidelines.
  7. ECOG performance status 0-1.
  8. Adequate organ function as defined by screening laboratory values within the following parameters:

    1. Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (off growth factors at least 72 h).
    2. Platelet count ≥100 × 10^3/μL without transfusion in the past 10 days.
    3. Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed).
    4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma glutamyl transferase (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.
    5. Total bilirubin ≤1.5 × ULN (patients with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN with direct bilirubin ≤1.5 × ULN).
    6. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft-Gault equation.
  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 must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks 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 16 weeks after the patient receives his last dose of camidanlumab tesirine

Exclusion Criteria:

  1. Participation in another investigational interventional study.
  2. Prior therapy with a CD25 (IL-2R) antibody within the last 4 months.
  3. Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody.
  4. Patients with prior solid organ or allogeneic bone marrow transplant.
  5. 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 I diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled).
  6. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis) or other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis).
  7. History of recent infection (within 4 weeks of C1D1) considered to be caused by one of the following pathogens: herpes simplex virus 1/2 (HSV1, HSV2), varicella zoster (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68.
  8. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Note: Testing is not mandatory to be eligible but should be considered in patients with high risk for these infections.
  9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
  10. Failure to recover to ≤Grade 1 (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v4.0]) from acute nonhematologic toxicity (to ≤Grade 2 for neuropathy or alopecia), due to previous therapy, prior to screening.
  11. Symptomatic CNS metastases or evidence of leptomeningeal disease (brain MRI or previously documented cerebrospinal fluid (CSF) cytology). Previously treated asymptomatic CNS metastases are permitted provided that the last treatment (systemic anticancer therapy and/or local radiotherapy) was completed ≥8 weeks prior to Day 1 except usage of low dose of steroids on a taper (i.e., up to 10 mg prednisone or equivalent on Day 1 and consecutive days is permissible if being tapered down). Patients with discrete dural metastases are eligible.
  12. 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).
  13. Active diarrhea CTCAE Grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
  14. Active infection requiring systemic antibiotic therapy.
  15. Active bleeding diathesis or significant anticoagulation (international normalized ratio [INR] ≥2.0).
  16. Breastfeeding or pregnant.
  17. Significant medical comorbidities, including uncontrolled hypertension (blood pressure [BP] ≥160 mmHg systolic and/or ≥110 mmHg diastolic repeatedly with or without anti hypertensive medication), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, severe uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, active ulceration of the upper gastrointestinal (GI) tract or GI bleeding, or severe chronic pulmonary disease.
  18. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. For cytotoxic agents that have major delayed toxicity, e.g., mitomycin C and nitrosoureas, 4 weeks is indicated as washout period. For patients receiving systemic anticancer immunotherapies (as opposed to intralesional) that lead to activation of Teffs and/or increase the Teff/Treg ratio, such as anti-PD-1 antibodies, 5 half-lives are indicated as the washout period.
  19. Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
  20. Patients requiring concomitant immunosuppressive agents or chronic treatment with corticosteroids except:

    • replacement dose steroids in the setting of adrenal insufficiency
    • topical, inhaled, nasal, and ophthalmic steroids are allowed
  21. Planned live vaccine administration after starting study drug (C1D1).
  22. Congenital long QT syndrome, or a corrected QTcF interval of ≥ 480 ms, at screening (unless secondary to pacemaker or bundle branch block).
  23. 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.
  24. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03621982


Contacts
Contact: Maria Cincotta Cincotta@adctherapeutics.com
Contact: Jay Feingold Jay.Feingold@adctherapeutics.com

Locations
United States, New York
Roswell Park Cancer Institute Not yet recruiting
Buffalo, New York, United States, 14263
Contact: Igor Puzanov, MD         
Sponsors and Collaborators
ADC Therapeutics S.A.

Responsible Party: ADC Therapeutics S.A.
ClinicalTrials.gov Identifier: NCT03621982     History of Changes
Other Study ID Numbers: ADCT-301-103
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ADC Therapeutics S.A.:
Camidanlumab tesirine

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Stomach Neoplasms
Head and Neck Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Esophageal Neoplasms
Triple Negative Breast Neoplasms
Pancreatic Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type