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Trial record 1 of 1 for:    NCT03621982
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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 : Recruiting
First Posted : August 9, 2018
Last Update Posted : September 23, 2020
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 Squamous Cell Carcinoma Non-small Cell Lung Cancer Gastric Cancer Esophageal Cancer Pancreas Cancer Bladder Cancer Renal Cell Carcinoma Melanoma Triple-negative Breast Cancer Ovarian Cancer Colo-rectal Cancer Drug: ADCT-301 Biological: Pembrolizumab 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 21 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: Non-Randomized
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) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors
Actual Study Start Date : November 9, 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: ADCT-301 Monotherapy
In Part 1 (dose escalation) patients will receive escalating doses of camidanlumab tesirine as monotherapy.
Drug: ADCT-301
intravenous infusion
Other Name: Camidanlumab tesirine

Experimental: ADCT-301 Combination Therapy

When the recommended dose of camidanlumab tesirine as single agent is determined, newly enrolled patients will receive escalating dose of camidanlumab tesirine in combination with pembrolizumab.

In Part 2 (expansion), there will be two groups:

Group 1: an indication for which camidanlumab tesirine in combination with pembrolizumab was shown in Part 1 to have preliminary activity.

Group 2: a basket group with the same indications allowed in Part 1, where patients will be treated with camidanlumab tesirine in combination with pembrolizumab with the exception for the one selected for Group 1.

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

Biological: Pembrolizumab
intravenous infusion
Other Name: Keytruda




Primary Outcome Measures :
  1. Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose Limiting toxicities as defined per protocol, as related to ADCT-301 [ Time Frame: Up to 3 years ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment.

  2. Number of Adverse Events of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
    Adverse events will be graded according to CTAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.

  3. Number of Serious Adverse Events (SAE) [ Time Frame: Up to 3 years ]
    A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization of 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 or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.

  4. Number of SAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
    AEs will be graded according to CTCAE v.4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.

  5. Number of Dose Interruptions and/or Dose Reductions [ Time Frame: Up to 3 years ]
  6. Number of Dose Limiting Toxicities [ Time Frame: Up to 3 years ]
  7. Number of Participants who Experience a Clinically Significant Change in Baseline in Laboratory Values [ Time Frame: Up to 3 years ]
  8. Number of Participants who Experience a Clinically Significant Change in Baseline in Vital Signs [ Time Frame: Up to 3 years ]
  9. Number of Participants who Experience a Clinically Significant Change in Baseline in Electrocardiogram (ECG) Results [ Time Frame: Up to 3 years ]
  10. Number of Particpants who Experience a Clinically Significant Change in Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Up to 3 years ]

Secondary Outcome Measures :
  1. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Up to 3 years ]
    Overall response rate (ORR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

  2. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Up to 3 years ]
    Duration of response (DOR) defined as the time from the first documentation of tumor response to disease progression as per RECIST v1.1

  3. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Up to 3 years ]
    Progression-free survival (PFS) defined as the time between start of treatment and the first documentation of recurrence or progression as per RECIST v1.1

  4. Evaluate the preliminary anti-tumor activity of camidanlumab tesirine [ Time Frame: Up to 3 years ]
    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: Up to 3 years ]
    Noncompartmental analysis of the maximum concentration (Cmax)

  6. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Up to 3 years ]
    Noncompartmental analysis of the time to maximum concentration (Tmax)

  7. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Up to 3 years ]
    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: Up to 3 years ]
    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: Up to 3 years ]
    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: Up to 3 years ]
    Noncompartmental analysis of the accumulation index (AI)

  11. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Up to 3 years ]
    Noncompartmental analysis of clearance (CL)

  12. Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum [ Time Frame: Up to 3 years ]
    Noncompartmental analysis of volume of distribution (Vd)

  13. Number of confirmed positive anti-drug antibody (ADA) responses [ Time Frame: Up to 3 years ]
    ADA titers if applicable, neutralizing activity to camidanlumab tesirine after treatment with camidanlumab tesirine.



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 camidanlumab tesirine as monotherapy:

    Selected advanced solid tumors: colorectal, head and neck, NSCLC, gastric and esophageal cancers, pancreas, bladder, renal cell carcinoma, melanoma, TNBC, and ovarian/fallopian tube cancers

    Part 1 Dose-escalation camidanlumab tesirine in combination with pembrolizumab:

    Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer, ovarian /fallopian tube cancer, pancreatic cancer, non-small cell lung cancer, and melanoma.

    Part 2 Dose expansion camidanlumab tesirine in combination with pembrolizumab:

    • Group 1: One of the indications identified in Part 1, for which at least 1 response (PR or CR) was seen.
    • Group 2: Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer, ovarian/fallopian tube cancer, pancreatic cancer, non-small cell lung cancer, melanoma, with the exception 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 immune-related Response Criteria (irRC)/ immune-related Response Evaluation Criteria In Solid Tumors (irRECIST)/ immune-related Response Evaluation Criteria In Solid Tumors (iRECIST)/ immune-modified Response Evaluation Criteria in Solid Tumors (imRECIST) as per Investigator discretion.
  6. A) For camidanlumab tesirine as monotherapy: 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.

    B) Patients included in the paired-biopsy cohort must in addition be willing to undergo fresh biopsy procedures (minimum 3 passes each) after receiving at least 1 dose of study drug.

    C) For camidanlumab tesirine in combination with pembrolizumab: Patient must have a site of disease amenable to biopsy and must provide fresh tumor biopsy prior to C1D1, and be willing to undergo fresh biopsy procedures (minimum 3 passes each) after receiving at least 1 dose of study treatment, 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 hours).
    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 (WOCBP).
  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 or 4 months after last dose of pembrolizumab, whichever is the latest. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 16 weeks after the patient receives his last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab, whichever is the latest.

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]) (patients 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) caused by a pathogen known to be associated with GBS, for example: 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, enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

    Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as polymerase chain reaction [PCR]) are mandatory and must be negative before initiating study treatment (tests to be performed 3 days or less prior to dosing on C1D1).

  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; testing is mandatory if status is unknown.
  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 version 4.0]) 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 ≥4 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, 4 weeks 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 within 30 days prior to the first dose of study treatment and during study treatment.
  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.
  25. For patients treated with camidanlumab tesirine in combination with pembrolizumab: patients intolerant to checkpoint-inhibitor or with a history of the following ≥ Grade 3 immune-related adverse events: hepatitis, renal, ocular, neurologic, cardiovascular, rheumatologic, and hematologic.
  26. For patient treated with camidanlumab tesirine in combination with pembrolizumab: patients with a history of non-infectious pneumonitis related to prior systemic treatment and that require treatment with steroids within the last 6 months prior to enrollment.

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
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Contact: ADC Therapeutics 954-903-7994 clinical.trials@adctherapeutics.com

Locations
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United States, California
Stanford Cancer Center Recruiting
Palo Alto, California, United States, 94304
Contact: Sukhmani K Padda, MD         
United States, Connecticut
Smilow Cancer Hospital Phase 1 Unit Recruiting
New Haven, Connecticut, United States, 06511
Contact: Patricia LoRusso, DO         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Igor Puzanov, MD         
United States, Tennessee
The Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Johanna C Bendell, MD         
United States, Texas
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Kyriakos P Papadopoulos, MD         
Sponsors and Collaborators
ADC Therapeutics S.A.
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Responsible Party: ADC Therapeutics S.A.
ClinicalTrials.gov Identifier: NCT03621982    
Other Study ID Numbers: ADCT-301-103
2019-003132-23 ( EudraCT Number )
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: September 23, 2020
Last Verified: September 2020

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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:
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Carcinoma
Carcinoma, Renal Cell
Triple Negative Breast Neoplasms
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Urogenital Neoplasms
Endocrine System Diseases
Digestive System Neoplasms
Digestive System Diseases
Urologic Neoplasms
Urologic Diseases
Adenocarcinoma
Kidney Neoplasms
Kidney Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Pancreatic Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents