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Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma

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ClinicalTrials.gov Identifier: NCT03685344
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : December 13, 2018
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics S.A.

Brief Summary:
The purpose of this Phase 1 study is to evaluate the safety and antitumor activity of Loncastuximab Tesirine (ADCT-402) and Durvalumab in Patients with Advanced Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Mantle Cell Lymphoma Follicular Lymphoma Drug: Loncastuximab Tesirine and Durvalumab Phase 1

Detailed Description:

This is a Phase 1b, open-label, single-arm combination study with a dose escalation phase (Part 1) followed by a dose expansion phase (Part 2). The study will enroll approximately 75 patients.

A standard 3+3 dose escalation design will be used for Part 1. The DLT period will be the 21 days after the first durvalumab dose.

Part 2 will consist of up to 3 expansion cohorts, one for DLBCL, one for MCL, and one for FL. Each cohort will be approximately 20 patients treated at the dose determined in Part 1.

The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3, 6' and 4 weeks), and a Follow-up Period (approximately every 12 week visits for up to 2 years after treatment discontinuation).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label Study to Evaluate the Safety and Antitumor Activity of Loncastuximab Tesirine and Durvalumab in Patients With Advanced Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma
Estimated Study Start Date : December 6, 2018
Estimated Primary Completion Date : July 8, 2020
Estimated Study Completion Date : July 6, 2022


Arm Intervention/treatment
Experimental: ADCT-402
A standard 3+3 dose escalation design will be used for Part 1. The DLT period will be the 21 days after the first durvalumab dose. Part 2 will consist of up to 3 expansion cohorts, one for DLBCL, one for MCL, and one for FL. Each cohort will be approximately 20 patients treated at the dose determined in Part 1.
Drug: Loncastuximab Tesirine and Durvalumab
intravenous (IV)
Other Name: ADCT-402 in combination with Durvalumab




Primary Outcome Measures :
  1. Safety and tolerability of loncastuximab tesirine in combination with durvalumab by frequency and severity of adverse events [ Time Frame: Until 30 days after last dose ]
    Frequency and severity of adverse events (AEs)

  2. Frequency and severity of serious adverse events (SAEs) [ Time Frame: Until 30 days after last dose ]
  3. Incidence of dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: First 21-day cycle for each patient (dose escalation only) ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
    ORR according to the 2014 Lugano classification, defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR)

  2. Complete Response Rate CR [ Time Frame: Up to 2 years ]
    Complete response rate defined as the percentage of treated patients with a BOR of CR

  3. Duration of response (time from first tumor response to disease progression or death) [ Time Frame: Up to 2 years ]
  4. Overall survival (time between the start of treatment and death from any cause) [ Time Frame: Up to 2 years ]


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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. Male or female patient aged 18 years or older
  2. Pathologic diagnosis of DLBCL, MCL, or FL
  3. Patients must have relapsed or refractory disease and have failed or been intolerant to standard therapy
  4. Patients who have received previous CD19-directed therapy must have a biopsy that shows CD19 expression after completion of the CD19-directed therapy
  5. Measurable disease as defined by the 2014 Lugano Classification
  6. Patients must be willing to undergo tumor biopsy
  7. ECOG performance status 0-1
  8. Screening laboratory values within the following parameters:

    1. Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth factors at least 72 hours)
    2. Platelet count ≥75 × 103/µL without transfusion in the past 7 days
    3. Hemoglobin ≥9.0 g/dL (5.59 mmol/L), transfusion allowed
    4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and GGT ≤2.5 × the upper limit of normal (ULN); ≤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)
    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 3 days prior to start of study drug on C1D1 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 study therapy. Men with female partners who are of childbearing potential must agree that they will 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 study therapy.

Exclusion Criteria:

  1. Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody.
  2. Previous therapy with any checkpoint inhibitor
  3. Autologous stem cell transplant within 100 days prior to start of study drug (C1D1)
  4. History of allogenic stem cell transplant
  5. History of solid organ transplant
  6. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:

    1. Patients with vitiligo or alopecia
    2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
    3. Any chronic skin condition that does not require systemic therapy
    4. Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
    5. Patients with celiac disease controlled by diet alone
  7. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice)
  8. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV)
  9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
  10. Lymphoma with active central nervous system (CNS) involvement at the time of screening, including leptomeningeal disease
  11. 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)
  12. Breastfeeding or pregnant
  13. Significant medical comorbidities, including but not limited to, 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 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease
  14. Radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor.
  15. Major surgery within 28 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  16. Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
  17. Planned live vaccine administration after starting study drug (C1D1)
  18. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from acute nonhematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening. Patients with an endocrine AE of Grade ≤2 from prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
  19. Congenital long QT syndrome or a corrected QTcF interval of >470 ms at screening (unless secondary to pacemaker or bundle branch block)
  20. History of another primary malignancy except for:

    1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product and of low potential risk for recurrence
    2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    3. Adequately treated carcinoma in situ without evidence of disease 21. History of active primary immunodeficiency
  21. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, 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): NCT03685344


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

Locations
United States, Texas
Baylor Scott & White Medical Center - Temple Recruiting
Temple, Texas, United States, 76508
Contact: Vinit G Kanur, MD         
Sponsors and Collaborators
ADC Therapeutics S.A.

Responsible Party: ADC Therapeutics S.A.
ClinicalTrials.gov Identifier: NCT03685344     History of Changes
Other Study ID Numbers: ADCT-402-104
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 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.:
Loncastuximab Tesirine in Combination with Durvalumab

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs