Status and phase
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About
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.
Full description
This is a Phase 1b, open-label, multi-center study in participants with previously untreated DLBCL, with a dose escalation part followed by dose expansion part.
Participants will be treated by loncastuximab tesirine in combination with R CHOP.
The duration of the study participation for each participant is defined as the time from the date of signed written informed consent to the completion of the follow-up period, withdrawal of consent, lost to follow-up, or death, whichever occurs first.
The study will include a Screening Period (of up to 28 days), a Treatment Period of 6 cycles (cycles of 3 weeks), and a Follow-up Period (approximately every 12 week visits) for up to approximately 3 years from end-of-treatment (EOT).
Sex
Ages
Volunteers
Inclusion criteria
Written informed consent must be obtained prior to any study procedures
Male or female participant aged 18 years or older
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
Measurable disease as defined by the 2014 Lugano Classification
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)
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Adequate organ function as defined by screening laboratory values within the following parameters:
Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility.
Left ventricular ejection fraction (LVEF) of ≥50%, assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan
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
Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a cluster of differentiation 19 (CD19) antibody
Previous therapy with loncastuximab tesirine, rituximab, anthracycline, or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
Known history of hypersensitivity to any component of study treatment (loncastuximab tesirine and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP])
Previous treatment for aggressive lymphoma (with exception of short corticosteroid course [up to 7 days] for symptom management)
Contraindication to receive granulocyte colony stimulating factors
Human immunodeficiency virus (HIV) seropositive with any of the following:
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
Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
History of Stevens-Johnson syndrome or toxic epidermal necrolysis
Lymphoma with active central nervous system involvement at the time of Screening, including leptomeningeal disease
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)
Breastfeeding or pregnant
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.
Active systemic bacterial, viral, fungal, or other infection requiring systemic treatment at the time of Screening
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
Use of any other experimental medication within 14 days prior to start of study drug (C1D1; cycle is 21 days)
Received live vaccine within 4 weeks of C1D1; cycle is 21 days
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)
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
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.
Primary purpose
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Data sourced from clinicaltrials.gov
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