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NCT03589469: LOTIS-2

Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Completed Phase 2 Results posted Last updated 29 August 2023
What this trial tests

Phase 2 trial testing Loncastuximab tesirine in Diffuse Large B-Cell Lymphoma Refractory in 145 participants. Completed in 9 August 2022.

Timeline
1 August 2018
Primary endpoint
24 May 2020
9 August 2022

Quick facts

Lead sponsorADC Therapeutics S.A.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment145
Start date1 August 2018
Primary completion24 May 2020
Estimated completion9 August 2022
Sites37 locations across Switzerland, Italy, United Kingdom, United States

Drugs / interventions tested

Conditions studied

Sponsor

ADC Therapeutics S.A. — full company profile →

Who can join

18 and older, any sex, with Diffuse Large B-Cell Lymphoma Refractory or Diffuse Large B-cell Lymphoma Recurrent. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) Primary · Up to 21.5 months

ORR, as determined by central review according to the 2014 Lugano classification, defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).

GroupValue95% CI
Loncastuximab Tesirine48.339.9 – 56.7
Duration of Response (DOR) Secondary · Up to 39 months

DOR defined as the time from the first documentation of tumor response to disease progression or death.

GroupValue95% CI
Loncastuximab Tesirine13.376.87 – NA
Complete Response (CR) Rate Secondary · Up to 39 months

CR rate defined as the percentage of treated participants with a best overall response (BOR) of CR.

GroupValue95% CI
Loncastuximab Tesirine24.818.0 – 32.7
Relapse-free Survival (RFS) Secondary · Up to 39 months

RFS was defined as the time from the documentation of CR to disease progression or death.

GroupValue95% CI
Loncastuximab TesirineNANA – NA
Progression-free Survival (PFS) Secondary · Up to 40 months

PFS was defined as the time between start of treatment and the first documentation of recurrence, progression, or death.

GroupValue95% CI
Loncastuximab Tesirine4.932.89 – 8.31
Overall Survival (OS) Secondary · Up to 43 months

OS was defined as the time between the start of treatment and death from any cause.

GroupValue95% CI
Loncastuximab Tesirine9.536.74 – 11.47
Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) Secondary · Up to 599 days

An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with treatment. A TEAE was an adverse event with an onset that began or worsened on or after the first dose date and until 30 days after the last dose date, or start of a new anticancer therapy/procedure, whichever came earlier. TEAE assessments also included those per the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade ≥3 AEs and serious TEAEs. AEs were

Any TEAE
GroupValue95% CI
Loncastuximab Tesirine143
Grade ≥3 TEAE
GroupValue95% CI
Loncastuximab Tesirine107
Serious TEAE
GroupValue95% CI
Loncastuximab Tesirine57
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests Secondary · Baseline up to 599 days

Clinical laboratory tests included hematology and chemistry. Clinically significant changes were determined by the Investigator.

GroupValue95% CI
Loncastuximab Tesirine83
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Secondary · Baseline up to 599 days

Vital sign measurements included arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.

GroupValue95% CI
Loncastuximab Tesirine0
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment Secondary · Baseline and end of treatment (up to 599 days)

ECOG (Eastern Cooperative Oncology Group) Performance Status is scored on a 6-point scale where higher scores indicate a worse outcome. ECOG scores include the following: * 0 = fully active, able to carry on all pre-disease performance without restriction * 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work * 2 = ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours * 3 = capable of only limited self-care; confined

Baseline
GroupValue95% CI
Loncastuximab Tesirine58
Loncastuximab Tesirine78
Loncastuximab Tesirine9
Loncastuximab Tesirine0
End of treatment
GroupValue95% CI
Loncastuximab Tesirine44
Loncastuximab Tesirine50
Loncastuximab Tesirine14
Loncastuximab Tesirine2
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs) Secondary · Baseline up to 599 days

Clinically significant changes from baseline for 12-lead ECGs were measured as abnormal QT interval corrected by Fridericia formula (QTcF) and QT interval corrected by Bazett formula (QTcB) values.

QTcB maximum change from baseline: >30, <=60 msec
GroupValue95% CI
Loncastuximab Tesirine30
QTcB maximum change from baseline: >60 msec
GroupValue95% CI
Loncastuximab Tesirine4
QTcF maximum change from baseline: >30, <=60 msec
GroupValue95% CI
Loncastuximab Tesirine23
QTcF maximum change from baseline: >60 msec
GroupValue95% CI
Loncastuximab Tesirine1
Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199 Secondary · Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose and end of infusion
Conjugated Antibody Cycle 1
GroupValue95% CI
Loncastuximab Tesirine2430± 38.8
Conjugated Antibody Cycle 2
GroupValue95% CI
Loncastuximab Tesirine2734± 35.8
Conjugated Antibody Cycle 3
GroupValue95% CI
Loncastuximab Tesirine1694± 47.6
Total Antibody Cycle 1
GroupValue95% CI
Loncastuximab Tesirine3267± 36.7
Total Antibody Cycle 2
GroupValue95% CI
Loncastuximab Tesirine3756± 31.3
Total Antibody Cycle 3
GroupValue95% CI
Loncastuximab Tesirine2581± 41.9
SG3199 Cycle 1
GroupValue95% CI
Loncastuximab Tesirine0.0410± 56.6
SG3199 Cycle 2
GroupValue95% CI
Loncastuximab Tesirine0.0490± 78.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 43 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Loncastuximab Tesirine
Serious: 57/145 (39%)
Deaths: 97/145

Serious adverse events (58 terms)

ReactionSystemLoncastuximab Tesirine
HypercalcaemiaMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Abdominal painGastrointestinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
Non-cardiac chest painGeneral disorders
PneumoniaInfections and infestations
HeadacheNervous system disorders
Mental status changesPsychiatric disorders
Acute kidney injuryRenal and urinary disorders
NeutropeniaBlood and lymphatic system disorders
PericarditisCardiac disorders
AscitesGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DysphagiaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Small intestinal perforationGastrointestinal disorders
Disease progressionGeneral disorders
Face oedemaGeneral disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
PainGeneral disorders
Other adverse events (44 terms — click to expand)

ReactionSystemLoncastuximab Tesirine
Gamma-glutamyltransferase increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Blood alkaline phosphatase increasedInvestigations
Oedema peripheralGeneral disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
Aspartate aminotransferase increasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
HypomagnesaemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
InsomniaPsychiatric disorders
HeadacheNervous system disorders
ErythemaSkin and subcutaneous tissue disorders
Photosensitivity reactionSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
HypocalcaemiaMetabolism and nutrition disorders
LymphopeniaBlood and lymphatic system disorders
TachycardiaCardiac disorders
HyperglycaemiaMetabolism and nutrition disorders
Weight increasedInvestigations
HypotensionVascular disorders
HyponatraemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders

Most-reported serious reactions: Hypercalcaemia, Febrile neutropenia, Pyrexia, Abdominal pain, Pleural effusion, Anaemia, Pericardial effusion, Non-cardiac chest pain.

Data from ClinicalTrials.gov NCT03589469 adverse events section.

Sponsor's own description

The purpose of this Phase 2 study is to evaluate the clinical efficacy and safety of Loncastuximab Tesirine (ADCT-402) in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  2. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial.
    Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, et al · · 2021 · cited 327× · PMID 33989558 · DOI 10.1016/s1470-2045(21)00139-x
  3. Emerging new therapeutic antibody derivatives for cancer treatment.
    Jin S, Sun Y, Liang X, Gu X, et al · · 2022 · cited 304× · PMID 35132063 · DOI 10.1038/s41392-021-00868-x
  4. 2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management.
    Susanibar-Adaniya S, Barta SK. · · 2021 · cited 250× · PMID 33661537 · DOI 10.1002/ajh.26151
  5. Antibodies to watch in 2022.
    Kaplon H, Chenoweth A, Crescioli S, Reichert JM. · · 2022 · cited 245× · PMID 35030985 · DOI 10.1080/19420862.2021.2014296
  6. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  7. Targeting cancer with antibody-drug conjugates: Promises and challenges.
    Dean AQ, Luo S, Twomey JD, Zhang B. · · 2021 · cited 145× · PMID 34291723 · DOI 10.1080/19420862.2021.1951427
  8. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma.
    Hamadani M, Radford J, Carlo-Stella C, Caimi PF, et al · · 2021 · cited 127× · PMID 33211842 · DOI 10.1182/blood.2020007512

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03589469.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing