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

NCT ID: NCT03685344

Last Updated: 2021-10-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-04
• Study Completion Date: 2020-10-27

Brief 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

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 participants.

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 participants 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).

Conditions

Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma; Follicular Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ADCT-402

Dose escalation phase: Ascending doses of Loncastuximab tesirine will be administered using a traditional 3+3 design. Dose level 1: 90 µg/kg, every 3 weeks (Q3W). Dose level 2: 120 µg/kg, Q3W. Dose level 3: 150 µg/kg, Q3W. Loncastuximab tesirine will be given for 2 doses, 3 weeks apart.

Dose expansion phase: Loncastuximab tesirine will be administered at the recommended dose determined in the dose escalation phase. Durvalumab will also be administered at a dose of 1500 mg once every 4 weeks (Q4W) throughout the dose escalation phase and dose expansion phase.

Group Type: EXPERIMENTAL

Loncastuximab Tesirine and Durvalumab

Intervention Type: DRUG

intravenous infusion

Interventions

Loncastuximab Tesirine and Durvalumab

intravenous infusion

Intervention Type: DRUG

Other Intervention Names

ADCT-402 in combination with Durvalumab; Zynlonta

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADC Therapeutics S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

UCH-MHS Memorial Hospital Centeral

Colorado Springs, Colorado, United States

University of Florida Health Shands Cancer Hospital

Gainesville, Florida, United States

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Icahm School of Medicine at Mount Sinai

New York, New York, United States

Baylor University Medical Center

Dallas, Texas, United States

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States

Baylor Scott & White Medical Center - Temple

Temple, Texas, United States

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon Pabellón de Oncología

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz Unidad de Limfomas Servicio de Hematologia

Madrid, , Spain

Hospital Universitario Virgen Macarena Servicio Oncologia Medica

Seville, , Spain

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Countries

United States; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002670-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ADCT-402-104

Identifier Type: -

Identifier Source: org_study_id