Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma

NCT04699461 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ADCT 402-2022020-003695-40
• Study Type: interventional
• Target: 6
• Locations: 10 countries
• Sites: 34

Brief Summary

This study aims to evaluate the efficacy of single agent loncastuximab tesirine compared to idelalisib in participants with relapsed or refractory follicular lymphoma.

Conditions

Relapsed Follicular Lymphoma; Refractory Follicular Lymphoma

Keywords

Relapsed Follicular Lymphoma; Refractory Follicular Lymphoma; Loncastuximab Tesirine; Follicular Lymphoma; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  CRR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR) assessed prior to any subsequent anticancer treatment.

  Up to the end of treatment, maximum time on treatment was 333 days

Secondary Outcomes (14)

• Overall Response Rate (ORR)

  Up to end of treatment, maximum time on treatment was 333 days

• Progression-Free Survival (PFS)

  Up to end of treatment, maximum time on treatment was 333 days

• Overall Survival (OS)

  Up to end of treatment, maximum time on treatment was 333 days

• Duration of Response (DOR)

  Up to end of treatment, maximum time on treatment was 333 days

• Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)

  Day 1 to 30 days after end of treatment, maximum time on treatment was 333 days

Study Arms (2)

Loncastuximab Tesirine

EXPERIMENTAL

Participants will be administered loncastuximab tesirine as an intravenous (IV) infusion on Day 1 of each cycle, where 1 cycle is 3 weeks. Loncastuximab tesirine will be administered at a dose of 150 μg/kg for 2 cycles, then at a dose of 75 μg/kg for subsequent cycles.

Drug: Loncastuximab Tesirine

Idelalisib

ACTIVE COMPARATOR

Participants will be administered 150 mg idelalisib, orally, twice a day throughout each cycle, where 1 cycle is 4 weeks.

Drug: Idelalisib

Interventions

Loncastuximab Tesirine DRUG

IV infusion

Also known as: Zynlonta, ADCT-402

Loncastuximab Tesirine

Idelalisib DRUG

Oral tablet

Idelalisib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any study procedures.
• Male or female participants aged 18 years or older, with pathologic diagnosis of follicular lymphoma (FL) (Grade 1, 2, 3A) in the most recent tumor biopsy.
• Relapsed or refractory disease following two or more treatment regimens, at least one of which must have contained an anti-CD20 therapy.
• Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy.
• Measurable disease as defined by the 2014 Lugano Classification as assessed by positron emission tomography - computed tomography (PET-CT) or, if not Fluorodeoxyglucose (FDG) avid, CT or magnetic resonance imaging (MRI).
• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available). Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Adequate organ function as defined by screening laboratory values within the following parameters:
• Absolute neutrophil count (ANC) ≥1.0 × 10\^3/μL (off growth factors at least 72 hours),
• Platelet count ≥75 × 10\^3/μL without transfusion in the past 2 weeks,
• Alanine aminotransferase, AST, and GGT ≤2.5 × the upper limit of normal (ULN),
• Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN),
• 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
• Women of childbearing potential (WOCBP)(1) must agree to use a highly effective method(2) of contraception from the time of giving informed consent until at least 9 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 giving informed consent until at least 6 months after the participant receives his last dose of study treatment.
• WOCBP are defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal. 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.

You may not qualify if:

• Previous treatment with loncastuximab tesirine.
• Previous treatment with idelalisib.
• History of hypersensitivity to any of the excipients of loncastuximab tesirine or idelalisib.
• Follicular lymphoma which has transformed to diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphomas.
• Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor, inducer, or sensitive substrate.
• History of or ongoing drug-induced pneumonitis.
• History of or ongoing inflammatory bowel disease.
• Any condition that could interfere with the absorption or metabolism of idelalisib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• Autologous transplant within 30 days prior to start of study treatment (C1D1).
• Allogenic transplant within 60 days prior to start of study treatment (C1D1).
• Active graft-versus-host disease.
• Post-transplantation lymphoproliferative disorders.
• Human immunodeficiency virus (HIV) seropositive with any of the following:
• CD4+ T-cell counts \<350 cells/μL.
• Acquired immuno-deficiency syndrome (AIDS)-defining opportunistic infection within 12 months prior to screening.

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (34)

Comprehensive Cancer Centers of Nevada - Central Valley

Las Vegas, Nevada, 89074, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Summit Medical Group - Florham Park Campus

Florham Park, New Jersey, 07932, United States

Location

Summit Medical Group

Florham Park, New Jersey, 07932, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Centre Hospitalier Universitaire Universite Catholique de Louvain

Yvoir, B-5530, Belgium

Location

Centre Hospitalier de Dunkerque

Dunkirk, 59385, France

Location

Centre Hospitalier de La Rochelle

La Rochelle, 17000, France

Location

Centre de Lutte Contre le Cancer - Centre Henri-Becquerel

Rouen, 76038, France

Location

Hôpital Bretonneau

Tours, 37044, France

Location

Semmelweis Egyetem

Budapest, 1088, Hungary

Location

Országos Onkológiai Intézet

Budapest, 1122, Hungary

Location

Pécsi Tudományegyetem Klinikai Központ

Pécs, 7624, Hungary

Location

Soroka Medical Center

Beersheba, 8410101, Israel

Location

Carmel Medical Center

Haifa, 3436212, Israel

Location

Rabin Medical Center - Beilinson Hospital

Petah Tikva, 4941492, Israel

Location

The Chaim Sheba Medical Center

Tel Aviv, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Azienda Ospedaliero - Universitaria Careggi

Florence, 50134, Italy

Location

Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością

Gdynia, 81-519, Poland

Location

Pratia Onkologia Katowice

Katowice, 40-519, Poland

Location

Pratia Poznań

Skorzewo, 60-185, Poland

Location

Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 08908, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Quirónsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Inselspital Universitätsspital Bern

Bern, 3010, Switzerland

Location

NHS Greater Glasgow and Clyde

Glasgow, G51 4TF, United Kingdom

Location

Account University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma

Interventions

loncastuximab tesirine; idelalisib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study was terminated (administrative decision) by the sponsor following the withdrawal of idelalisib from the US market for the relapsed FL indication (i.e., not due to any safety reasons emerging from this study).

Results Point of Contact

• Title: Contact ADC Therapeutics
• Organization: ADC Therapeutics

clinical.trials@adctherapeutics.com

954-903-7994

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 7, 2021
• Study Start: November 4, 2021
• Primary Completion: November 25, 2022
• Study Completion: November 25, 2022
• Last Updated: October 23, 2023
• Results First Posted: October 23, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); PL (3); US (5); IT (1); FR (4); ES (8); BE (2); HU (3); IL (5); CH (1)