LOTIS 6: Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma

Sponsor
ADC Therapeutics S.A. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04699461
Collaborator
(none)
6
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2
37.8
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
6 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Randomized Study of Loncastuximab Tesirine Versus Idelalisib in Patients With Relapsed or Refractory Follicular Lymphoma (LOTIS 6)
Actual Study Start Date :
Nov 4, 2021
Anticipated Primary Completion Date :
Dec 2, 2024
Anticipated Study Completion Date :
Dec 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Loncastuximab Tesirine

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
IV infusion
Other Names:
  • Zynlonta
  • ADCT-402
  • Active Comparator: Idelalisib

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

    Drug: Idelalisib
    Oral tablet

    Outcome Measures

    Primary Outcome Measures

    1. Complete Response Rate (CRR) [Up to 3 years after the last treatment]

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [Up to 3 years after the last treatment]

    2. Progression-Free Survival (PFS) [Up to 3 years after the last treatment]

    3. Overall Survival (OS) [Up to 3 years after the last treatment]

    4. Duration of Response (DOR) [Up to 3 years after the last treatment]

    5. Number of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE) [Up to 3 years after the last treatment]

    6. Number of Participants Who Experience at Least One Serious Adverse Event (SAE) [Up to 3 years after the last treatment]

    7. Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results [Baseline to end of treatment (up to approximately 30 months)]

    8. Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements [Baseline to end of treatment (up to approximately 30 months)]

    9. Number of Participants Who Experience a Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Results [Baseline to end of treatment (up to approximately 30 months)]

    10. Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [Baseline to end of treatment (up to approximately 30 months)]

    11. Average Concentration of Loncastuximab Tesirine Before Infusion [Day 1 to end of treatment (up to approximately 30 months)]

    12. Average Concentration of Loncastuximab Tesirine at the End of Infusion [Day 1 to end of treatment (up to approximately 30 months)]

    13. Clearance Rate of Loncastuximab Tesirine [Day 1 to end of treatment (up to approximately 30 months)]

    14. Volume of Distribution of Loncastuximab Tesirine [Day 1 to end of treatment (up to approximately 30 months)]

    15. Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine [Up to 3 years after the last treatment]

    16. Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) [Baseline up to 1 year after the last treatment]

    17. Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) [Baseline up to Cycle 18, where each cycle is 3 weeks]

    18. Number of Participants with Specific Symptomatic Adverse Event Symptoms As Selected from Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [Up to Week 27]

      The specific symptomatic adverse events includes fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough.

    19. Treatment-Related Symptoms as Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [Up to Week 27]

      The specific symptoms assessed include fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough. The severity is assessed from "None" to "Very severe" and the interference level is assessed from "Not at all" to "Very much."

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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:

    1. Absolute neutrophil count (ANC) ≥1.0 × 10^3/μL (off growth factors at least 72 hours),

    2. Platelet count ≥75 × 10^3/μL without transfusion in the past 2 weeks,

    3. Alanine aminotransferase, AST, and GGT ≤2.5 × the upper limit of normal (ULN),

    4. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN),

    5. 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.
    1. 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.

    2. 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 associated with inhibition of ovulation (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:
    • 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.

    • Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic 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.

    • 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:

    1. CD4+ T-cell counts <350 cells/μL.

    2. Acquired immuno-deficiency syndrome (AIDS)-defining opportunistic infection within 12 months prior to screening.

    3. Not on anti-retroviral therapy, or on anti-retroviral therapy for < 4 weeks at the time of screening.

    4. HIV viral load ≥400 copies/mL.

    • Serologic evidence of chronic hepatitis B infection and unable or unwilling to receive standard prophylactic anti-viral therapy or with detectable hepatitis B virus (HBV) viral load.

    • Serologic evidence of hepatitis C infection without completion of curative treatment or with detectable hepatitis C virus (HCV) viral load.

    • History of Stevens-Johnson syndrome or toxic epidermal necrolysis.

    • Lymphoma with active central nervous system involvement, 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 (BP ≥160/100 mm Hg 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.

    • Any Grade ≥3 active infection which requires IV antibiotics, IV antiviral, or IV antifungal treatment.

    • Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study treatment (C1D1), except shorter if approved by the Sponsor.

    • Use of any other experimental medication within 30 days prior to start of study treatment (C1D1).

    • Live vaccine administration within 4 weeks prior to Cycle(C) 1 Day (D) 1.

    • Failure to recover to ≤ Grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (except ≤Grade 2 neuropathy or alopecia) due to previous therapy prior to screening.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Comprehensive Cancer Centers of Nevada - Central Valley Las Vegas Nevada United States 89074
    2 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    3 Summit Medical Group - Florham Park Campus Florham Park New Jersey United States 07932
    4 Summit Medical Group Florham Park New Jersey United States 07932
    5 Hollings Cancer Center Charleston South Carolina United States 29425
    6 Universitair Ziekenhuis Gent Gent Belgium 9000
    7 Centre Hospitalier Universitaire Universite Catholique de Louvain Yvoir Belgium B-5530
    8 Centre Hospitalier de Dunkerque Dunkerque France 59385
    9 Centre Hospitalier de La Rochelle La Rochelle France 17000
    10 Centre de Lutte Contre le Cancer - Centre Henri-Becquerel Rouen France 76038
    11 Hôpital Bretonneau Tours Cedex 9 France 37044
    12 Semmelweis Egyetem Budapest Hungary 1088
    13 Országos Onkológiai Intézet Budapest Hungary 1122
    14 Pécsi Tudományegyetem Klinikai Központ Pécs Hungary 7624
    15 Soroka Medical Center Be'er Sheva Israel 8410101
    16 Carmel Medical Center Haifa Israel 3436212
    17 Rabin Medical Center - Beilinson Hospital Petah tikva Israel 4941492
    18 The Chaim Sheba Medical Center Tel Aviv Israel 52621
    19 Tel Aviv Sourasky Medical Center Tel Aviv Israel 6423906
    20 Azienda Ospedaliero - Universitaria Careggi Firenze Italy 50134
    21 Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością Gdynia Poland 81-519
    22 Pratia Onkologia Katowice Katowice Poland 40-519
    23 Pratia Poznań Skorzewo Poland 60-185
    24 Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet) L'Hospitalet De Llobregat Spain 08908
    25 Hospital Universitari Arnau de Vilanova Lleida Spain 25198
    26 Hospital Universitario Ramón y Cajal Madrid Spain 08908
    27 Hospital General Universitario Gregorio Marañón Madrid Spain 28007
    28 Hospital Universitario Fundación Jiménez Díaz Madrid Spain 28040
    29 Hospital Universitario La Paz Madrid Spain 28046
    30 Hospital Universitario Quirónsalud Madrid Pozuelo De Alarcón Spain 28223
    31 Hospital Universitario Virgen del Rocío Sevilla Spain 41013
    32 Inselspital Universitätsspital Bern Bern Switzerland 3010
    33 NHS Greater Glasgow and Clyde Glasgow United Kingdom G51 4TF
    34 Account University College London Hospitals NHS Foundation Trust London United Kingdom NW1 2PG

    Sponsors and Collaborators

    • ADC Therapeutics S.A.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    ADC Therapeutics S.A.
    ClinicalTrials.gov Identifier:
    NCT04699461
    Other Study ID Numbers:
    • ADCT 402-202
    • 2020-003695-40
    First Posted:
    Jan 7, 2021
    Last Update Posted:
    Jul 27, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by ADC Therapeutics S.A.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 27, 2022