Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma
Condition: Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma; Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Loncastuximab Tesirine and Durvalumab
Intervention description: intravenous infusion
Intervention MeSH terms: Durvalumab; Loncastuximab tesirine; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Loncastuximab Tesirine in Combination with Durvalumab

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

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female participants aged 18 years or older

          2. Pathologic diagnosis of DLBCL, MCL, or FL

          3. Participants must have relapsed or refractory disease and have failed or been
             intolerant to standard therapy

          4. Participants 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. Participants 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. Total bilirubin ≤1.5 × ULN (participants 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. Participants with vitiligo or alopecia

               2. Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement

               3. Any chronic skin condition that does not require systemic therapy

               4. Participants without active disease in the last 5 years may be included but only
                  after consultation with the Study Physician

               5. Participants 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 non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due
             to previous therapy prior to screening.

         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. History of active primary immunodeficiency or 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 participant at risk.