2022-501601-12-00
Completed
Phase 2
A Phase 2 Open-label Study of Loncastuximab Tesirine in Combination with Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Patients with Diffuse Large B-cell Lymphoma (DLBCL) (LOTIS-9)
ADC Therapeutics S.A., ADC Therapeutics S.A.12 sites in 2 countries28 target enrollmentStarted: February 27, 2023Last updated:
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- ADC Therapeutics S.A., ADC Therapeutics S.A.
- Enrollment
- 28
- Locations
- 12
- Primary Endpoint
- Cohort A • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Overview
Brief Summary
Cohort A To assess the efficacy of a response-adapted treatment of Lonca-R in unfit patients with previously untreated DLBCL, or HGBCL, or Grade 3b FL Cohort B To assess the tolerability and efficacy of a response-adapted treatment of Lonca-R in frail patients or patients with cardiac comorbidities with previously untreated DLBCL, or HGBCL, or Grade 3b FL, who are ineligible for standard R-mini-CHOP
Study Design
- Allocation
- Not Applicable
- Primary Purpose
- A Phase 2 Open-label Study Of Loncastuximab Tesirine In Combination With Rituximab (lonca-r) In Prev
- Masking
- None
Eligibility Criteria
- Ages
- 65 years to 65+ years (65+ Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female
- •Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization (WHO) classification (including patients with DLBCL transformed from indolent lymphoma), or high-grade B cell lymphoma (HGBCL), or Grade 3b follicular lymphoma (FL).
- •Measurable disease as defined by the 2014 Lugano Classification
- •Stages I-IV
- •ECOG PS 0-2; ECOG PS 3 allowed if decline in status is deemed related to lymphoma & felt to be potentially reversible by the treating physician
- •Adequate organ function as defined by screening laboratory values within the following parameters: a. Absolute neutrophil count (ANC) ≥ 1.0 × 10^3/µL (off growth factors at least 72 hours) b. Platelet count ≥ 75 × 10^3/µL without transfusion in the past 7 days c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤ 2.5 × the upper limit of normal (ULN) d. Total bilirubin ≤ 1.5 × ULN (patients with known Gilbert’s syndrome may have a total bilirubin up to ≤ 3 × ULN) e. Calculated creatinine clearance > 30 mL/min by the Cockcroft and Gault equation
- •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 12 months after the last dose of study treatment. 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 the first dose until at least 7 months after the patient receives her/his last dose of study treatment
- •Inclusion Criteria specific for Cohort A: Unfit as defined by the sGA (includes all of the following): a. Aged ≥ 80 years b. ADL score of 6 c. IADL score of 8 d. CIRS-G: no score of 3-4 and < 5 scores of 2
- •Inclusion Criteria specific for Cohort B: Frail as defined by the sGA: a. Aged ≥ 80 years b. ADL score of < 6 and/or c. IADL score of < 8 and/or d. CIRS-G ≥ 1 score of 3-4 and/or ≥ 5 scores of 2 OR Aged ≥ 65 - <80 with at least one of the following cardiac comorbidities that make anthracycline-containing regimens inadvisable as determined by the investigator. a. Left ventricular ejection fraction (LVEF) ≥ 30 to < 50% b. History of myocardial infarction within 6 months prior to screening c. Ischemic heart disease d. History of stroke within 12 months prior to screening
Exclusion Criteria
- •Known history of hypersensitivity to or positive serum human anti-drug antibody to a CD19 antibody
- •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)
- •Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1 [C1D1]), except shorter if approved by the Sponsor
- •Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
- •Received live vaccine within 4 weeks of C1D1
- •Congenital long QT syndrome or a corrected 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 patient inappropriate for study participation or put the patient at risk
- •Previous therapy for DLBCL, HGBCL, Grade 3b FL (with exception of corticosteroid course for symptom management of less than 14 days)
- •Previous therapy with loncastuximab tesirine and rituximab for any indication
Outcomes
Primary Outcomes
Cohort A • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort A • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort B • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort B • CR rate defined as proportion of patients with a BOR of CR according to the 2014 Lugano Classification criteria
Cohort B • Tolerability as defined by the percentage of patients completing a total of 4 cycles of therapy divided by the total number of patients.
Cohort B • Tolerability as defined by the percentage of patients completing a total of 4 cycles of therapy divided by the total number of patients.
Secondary Outcomes
- ORR according to the 2014 Lugano Classification defined as the proportion of patients with a BOR of CR or PR.
- 2 year PFS, defined as the proportion of patients that are PFS event-free at 2 years
- 3 year overall survival (3-yr OS), defined as the proportion of patients that are OS event-free at 3 years.
- Duration of response (DoR) defined as the time from the first documentation of tumor response (CR or PR) to disease progression or death
- Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
- Changes from baseline in safety laboratory variables, vital signs, physical examinations, Eastern Cooperative Oncology Group scale of performance status (ECOG PS)
- Concentrations and PK parameters of loncastuximab tesirine pyrrolobenzodiazepine (PBD)-conjugated antibody, total antibody, and SG3199 unconjugated warhead
- Frequency of confirmed positive anti-drug antibody (ADA) responses, their associated titers and, if applicable, neutralizing activity to loncastuximab tesirine after treatment with loncastuximab tesirine when given in combination with rituximab
- Changes in patient-reported outcomes (e.g., symptoms, functions, and overall health status) from baseline as evaluated by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
Investigators
Clinical Operations
Scientific
ADC Therapeutics S.A.
Study Sites (12)
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