A Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of Loncastuximab Tesirine in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untre

Not yet recruiting
Trial end date:
Target enrollment:
Participant gender:
The primary objective of this study is to characterize the safety and tolerability of loncastuximab tesirine in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, and identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for the combination therapy.
Phase 1
Accepts Healthy Volunteers?
Lead Sponsor:
ADC Therapeutics S.A.
Loncastuximab tesirine
Inclusion Criteria:

1. Written informed consent must be obtained prior to any study procedures

2. Male or female participant aged 18 years or older

3. Pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL), as defined by the 2016
World Health Organization classification (including participants with DLBCL
transformed from indolent lymphoma), or high-grade B cell lymphoma

4. Measurable disease as defined by the 2014 Lugano Classification

5. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue sample. (If
tissue block is not available, slides from a FFPE block may be acceptable for
eligibility upon consultation with the Sponsor)

6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

7. Adequate organ function as defined by screening laboratory values within the following

1. Absolute neutrophil count ≥1.5 × 10^3/μL (off growth factors at least 72 hours)

2. Platelet count ≥75 × 10^3/μL without transfusion in the past 7 days

3. Hemoglobin ≥9 g/dL (4.96 mmol/L), transfusion allowed

4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma
glutamyl transferase (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. Calculated creatinine clearance >30 mL/min by the Cockcroft and Gault equation

Note: A laboratory assessment may be repeated a maximum of two times during the
Screening period to confirm eligibility.

8. Left ventricular ejection fraction (LVEF) of ≥50%, assessed by echocardiography or
cardiac multi-gated acquisition (MUGA) scan

9. Women of childbearing potential (WOCBP) must agree to use a highly effective method of
contraception from the time of giving informed consent until at least 9 months after
the last dose of study drug. 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 6 months after the last dose of study drug.

Women of childbearing potential are defined as sexually mature women who have not undergone
bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been
postmenopausal (i.e., who have not menstruated at all) for at least one year. A
postmenopausal state is defined as no menses for 12 months without an alternative medical
cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be
used to confirm a postmenopausal state in women not using hormonal contraception or
hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single
FSH measurement is insufficient.

Highly effective forms of birth control are methods that achieve a failure rate of less
than 1% per year when used consistently and correctly. Highly effective forms of birth
control include: hormonal contraceptives (oral, injectable, patch, intrauterine devices),
male partner sterilization, or total abstinence from heterosexual intercourse, when this is
the preferred and usual lifestyle of the participant.

Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with
spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal,
post ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and
spermicide-only are not acceptable as highly effective methods of contraception.

Exclusion Criteria:

1. Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA)
to a cluster of differentiation 19 (CD19) antibody

2. Previous therapy with loncastuximab tesirine, rituximab, anthracycline, or
cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)

3. Known history of hypersensitivity to any component of study treatment (loncastuximab
tesirine and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

4. Previous treatment for aggressive lymphoma (with exception of short corticosteroid
course [up to 7 days] for symptom management)

5. Contraindication to receive granulocyte colony stimulating factors

6. Human immunodeficiency virus (HIV) seropositive with any of the following:

1. Cluster of differentiation 4 (CD4) + T-cell (CD4+) counts <350 cells/μL

2. Acquired immunodeficiency syndrome-defining opportunistic infection within 12
months prior to screening

3. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the
time of Screening

4. HIV viral load ≥400 copies/mL

7. Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or
unwilling to receive standard prophylactic antiviral therapy or with detectable HBV
viral load

8. Serologic evidence of hepatitis C virus (HCV) infection without completion of curative
treatment or with detectable HCV viral load

9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis

10. Lymphoma with active central nervous system 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. Active systemic bacterial, viral, fungal, or other infection requiring systemic
treatment at the time of Screening

15. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14
days prior to start of study drug (Cycle 1 Day 1 [C1D1]; cycle is 21 days), except
shorter if approved by the Sponsor

16. Use of any other experimental medication within 14 days prior to start of study drug
(C1D1; cycle is 21 days)

17. Received live vaccine within 4 weeks of C1D1; cycle is 21 days

18. Congenital long measure between Q wave and T wave in the electrocardiogram (QT)
syndrome or a corrected Fridericia correction of the QT measure (QTcF) interval of
>480 ms at Screening (unless secondary to pacemaker or bundle branch block)

19. 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

20. Any other significant medical illness, abnormality, or condition that would, in the
Investigator's judgment, make the participant inappropriate for study participation or
put the participant at risk.