Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Participants With Relapsed and/or Refractory DLBCL and Other Forms of NHL

Debiopharm International SA100 enrolled

Overview

The primary purpose of the study was to determine the safety and tolerability, anti-tumor activity of the proposed Debio 1562 dose regimens in combination with rituximab.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

100

Conditions

Diffuse Large B-Cell Lymphoma B-cell Non-Hodgkin's Lymphoma

Interventions

Debio 1562DRUG

Administered as IV Infusion.

RituximabDRUG

Administered as IV Infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * For Part 1 of the study, participants must have histopathologically confirmed diagnosis of R/R, DLBCL, FL, MZL/MALT, MCL, or other Sponsor approved NHL subtypes according to the World Health Organization (WHO) classification 2008 for which standard measures do not exist or are no longer effective. * For Part 2 and Part 3 of the study, participants must have histopathologically and clinically confirmed diagnosis of relapsed DLBCL. Participants will be considered to have a relapsed disease if they showed a duration of response of at least 24 weeks after their first line of therapy. The following participants with relapsed DLBCL will be enrolled: 1. Participants who received only one line of previous therapy and achieved either complete response (CR) or partial response (PR) for at least 24 weeks (from the last day of the last cycle) after their first line of therapy, but are not eligible for high dose chemotherapy with autologous stem cell transplantation (HD-ASCT) 2. Participants who received more than one line of previous therapy (including HD-ASCT), and have achieved a duration of response (CR or PR) of at least 8 weeks (from the last day of the last cycle) after their last line of therapy * Participants must have evaluable or measurable disease in accordance with the International Working Group Guidelines for Lymphoma. * Participants must have received at least one but no more than six prior treatment regimens. Prior treatment with an anti-cluster of differentiation 20 (anti-CD20) agent, either alone or in combination, is allowed. * Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2. * Participants who are Hepatitis B surface antigen positive (HBsAg+) (must be polymerase chain reaction (PCR) negative) who are taking antivirals, are allowed to enroll. Exclusion Criteria: * Participants with a diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). * For Part 2 and Part 3 of the study, participants with primary refractory DLBCL (defined as progression of disease within 24 weeks after first line of treatment). * For Part 2 and Part 3 of the study, participants that are eligible to undergo first time HD-ASCT. * For Part 2 and Part 3 of the study, participants with R/R FL, MZL/MALT, MCL, or any other NHL subtypes according to the WHO classification. * Participants with active hepatitis A, B or C infection. * Women who are pregnant or breast feeding. * Participants who have received prior therapy with other anti-CD37-targeting therapy. * Participants who have known central nervous system, meningeal, or epidural disease including brain metastases. * Participants with impaired cardiac function or clinically significant cardiac disease. * Participants currently presenting interstitial lung disease, diffuse parenchymal lung disease, or with a past history of severe/Grade 3 parenchymal lung disorders.

Locations (39)

Outcomes

Primary Outcomes

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An AE was defined as any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. This included exacerbation of a pre-existing condition. AEs included worsening (change in nature, severity, or frequency) of conditions present at the onset of the study, intercurrent illnesses, drug interactions, events related to or possibly related to concomitant medications, abnormal laboratory values (this included significant shifts from baseline within the range of normal that the Investigator considered to be clinically important), clinically significant abnormalities in physical examination, vital signs, and weight.

Time frame: Up to 30 days after end of treatment (EOT) (Up to 38 months)

Number of Participants With Clinically Significant Changes in Clinical Laboratory Test Results Reported as TEAEs

The clinical laboratory tests included Hematology: Hematocrit (Hct), hemoglobin (Hgb), platelet count, red blood cell (RBC) count, white blood cell (WBC) count with differential; Serum Chemistry: Albumin (ALB), alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), calcium (Ca), chloride (Cl), creatinine, glucose, lactate dehydrogenase (LDH), magnesium, phosphorus, potassium (K), sodium (Na), total bilirubin, total protein, uric acid, immunoglobulin levels (IgG, IgA, IgM); Urinalysis: Appearance, specific gravity and pH, evaluation of glucose, protein, bilirubin, ketones, leukocytes and blood; Coagulation: Prothrombin time (PT) or international normalized ratio (INR), activated partial thromboplastin time (aPTT).

Time frame: Up to 30 days after EOT (Up to 38 months)

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs

A standard 12-lead ECG was performed.

Time frame: Up to 30 days after EOT (Up to 38 months)

Number of Participants With Clinically Significant Changes in Vital Sign Measurements Reported as TEAEs

Data from ClinicalTrials.gov

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Alabama Oncology

Birmingham, Alabama, United States

Carle Foundation Hospital, Cancer Center

Urbana, Illinois, United States

Abbott Northwestern Hospital, Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Novant Health Oncology

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, United States

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, United States

Baylor University Medical Center

Dallas, Texas, United States

Swedish Medical Center

Seattle, Washington, United States

CHU UCL Namur asbl - Site Godinne

Yvoir, Namur, Belgium

...and 29 more locations

Secondary Outcomes

Maximum Plasma Drug Concentration (Cmax) of Debio 1562 and Rituximab

Time frame: Parts 1, 2/3: Pre and Post infusion: 5 min-Day (D) 1 of Cycles (C) 1-8 and 2 hours (h)-D1 of C1-2 (for Part 2/3), 24h-D2, 48h-D3 and D8, 15 of C1, 2; D1 of Month 37 (EOT) (rituximab only) and Month 38 (follow-up) (Cycle=21 days)

Area Under the Time-concentration Curve From Time 0 to t (AUC0-t) of Debio 1562 and Rituximab

Time frame: Parts 1, 2/3: Pre-dose, post infusion-5 min on Day 1 of C 1-6, 5 min on Day 1 of C 7, 8 and 2 h on Day 1 of C 1, 2 (only for Part 2/3), 24 h on Day 2, 48 h on Day 3, Days 8 and 15 of C 1, 2 (Cycle=21 days); EOT (up to 37 months), 30-day follow up

Area Under the Time-concentration Curve From Time 0 to Infinity (AUC0-inf) of Debio 1562 and Rituximab

Terminal Half-life (t1/2) of Debio 1562 and Rituximab

Clearance (CL) of Debio 1562 and Rituximab

Volume of Distribution at Steady State (Vss) of Debio 1562 and Rituximab

Time to Maximum Plasma Concentration (Tmax) of Debio 1562 and Rituximab

Progression-free Survival (PFS)

PFS was defined as the duration between the first dose date of Debio 1562 and the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD is defined as the new or clear progression of preexisting non-measured lesions or regrowth of previously resolved lesions or a new node \>1.5 cm in any axis or an abnormal lesion with \>1.5 cm longest transverse diameter or increase by \>50% of lesion.

Time frame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first

Time to Response (TTR)

TTR was defined as the duration between the first dose date of Debio 1562 and the date of first objective response (PR or CR). CR was defined as disappearance of all target lesions, no new lesions formation. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to ≤ 1.5 cm. PR was defined as ≥50% decrease in the sum of diameters of up to 6 target measurable nodes or extranodal sites, no new lesions formation.

Time frame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first

Duration of Response (DOR)

DOR was defined as duration between date of the first objective response (PR or CR) and date of PD or death due to any cause, whichever occurs first. CR: Disappearance of all target lesions, no new lesions formation, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to ≤1.5 cm. PR: ≥50% decrease in sum of diameters of up to 6 target measurable nodes or extranodal sites, no new lesions formation. PD: New or clear progression of preexisting non-measured lesions or regrowth of previously resolved lesions or a new node \>1.5 cm in any axis or an abnormal lesion with \>1.5 cm longest transverse diameter or increase by \>50% of lesion.

Time frame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first

Overall Survival (OS)

OS was defined as the duration between the first dose date of Debio 1562 and the date of death due to any cause.

Time frame: Up to death or end of study (approximately 57 months) or one year from the last participant's first dose

Number of Participants With Anti-drug Antibodies (ADA) for Debio 1562

The potential immunogenicity against Debio 1562 was assessed in an ADA population.

Time frame: Part 1: Pre-dose on Day 1 of Cycle(C)1 to 8; Part 2/3: Pre-dose on Day 1 of C1 to 6 and on Day 1 of C7 for participants who received treatment beyond C6 (each C=21 days); Parts 1, 2/3: Month 37 (EOT) and Month 38 (30-Day FU visit) (Cycle=21 days)