Efficacy and Safety Trial of Epcoritamab with or without Lenalidomide as First Line Therapy for Subjects with Diffuse Large B-Cell Lymphoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab A/S

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jan 2023 → ongoing

Decision date (initial)

2024-01-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Genmab A/S

External identifiers

EU CT number

2023-504832-16-00

EudraCT number

2021-005744-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Others, Safety

Evaluate the clinical efficacy of epcoritamab monotherapy or epcoritamab and lenalidomide

Secondary objectives 5

1. Evaluate other efficacy measures of epcoritamab monotherapy or epcoritamab and lenalidomide
2. Evaluate safety and tolerability of epcoritamab monotherapy or epcoritamab and lenalidomide
3. Evaluate immunogenicity
4. Assess the pharmacokinetics of epcoritamab
5. Evaluate patient-reported outcomes related to lymphoma symptoms

Conditions and MedDRA coding

DIFFUSE LARGE B CELL LYMPHOMA

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Must have newly diagnosed CD20+ large cell lymphoma.
2. Is ineligible for anthracycline-based therapy/cytotoxic chemotherapy due to: oBeing age ≥80 years; AND/OR oBeing age ≥75 years and having important comorbid condition(s), which are likely to have a negative impact on tolerability of anthracycline-based therapy/cytotoxic chemotherapy, Have Immune Effector Cell-Associated Encephalopathy (ICE) score of at least 8 out of 10.
3. Have Ann Arbor Stage II-IV disease.
4. Have ECOG PS of 0, 1, or 2; (ECOG PS of 3 may be considered if impairment is attributed to current lymphoma/DLBCL and if pre-phase treatment during the screening phase results in an improvement of ECOG PS to ≤2 prior to enrollment.)
5. Have measurable disease as per Lugano criteria.
6. Have acceptable organ function based on baseline bloodwork.
7. Must have fresh (preferred) or archival biopsy material at screening.

Exclusion criteria 11

1. Has known active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection at trial enrollment, including COVID-19 infection.
2. Has severe cardiovascular disease (other than those eligibility criteria that preclude the subject from receiving anthracycline-based therapy/cytotoxic chemotherapy).
3. Has been exposed to/received any of the following prior therapies, treatments, or procedures within the specified timeframes: oMajor surgery within 4 weeks prior to the first dose of epcoritamab; oNon-investigational antineoplastic agents or any investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of epcoritamab; oAutologous hematopoietic stem cell transplantation (HSCT), CAR-T, allogeneic stem cell transplantation, or solid organ transplantation; oLive, attenuated vaccines within 30 days prior to initiation of epcoritamab; oInvestigational vaccines within 28 days before the planned first dose of epcoritamab (ie, experimental and/or non-authorized SARS-CoV-2 vaccinations and therapies are not allowed); oInvasive investigational medical device use within 28 days before the planned first dose of epcoritamab.
4. Has primary central nervous system (CNS) tumor or known CNS involvement or intracranial involvement as confirmed by mandatory brain magnetic resonance imaging/computed tomography (MRI/CT) scan at screening and, if clinically indicated, by lumbar puncture.
5. Has a seizure disorder requiring anti-epileptic therapy or experienced a seizure within 6 months of signing an informed consent form.
6. Has known past or current malignancy other than inclusion diagnosis, with exceptions as stated in protocol.
7. Has known or suspected allergies, hypersensitivity, or intolerance to either of the trial treatments or has known or suspected contraindication to the use of all locally available anti-cytokine therapies per local guidelines for management of cytokine release syndrome (CRS).
8. Has active hepatitis B virus (HBV) (DNA polymerase chain reaction [PCR]-positive) or hepatitis C virus (HCV) (RNA PCR-positive) infection, current alcohol abuse, or cirrhosis.
9. Has active cytomegalovirus (CMV) infection (DNA PCR-positive) requiring treatment.
10. Has suspected active or inadequately treated latent tuberculosis.
11. Has a known history of seropositivity for HIV. Note: HIV testing is required at screening only if required per local health authorities or institutional standards.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response (CR) rate determined by Lugano criteria

Secondary endpoints 14

1. Duration of response (DOR) determined by Lugano criteria
2. Duration of complete response (DOCR) determined by Lugano criteria
3. Time to response (TTR) determined by Lugano criteria
4. Overall response rate (ORR) determined by Lugano criteria
5. Progression-free survival (PFS) determined by Lugano criteria
6. Time to next (anti-lymphoma) therapy (TTNT).
7. Rate and duration of minimal residual disease (MRD) negative status
8. Overall survival (OS)
9. Incidence of dose-limiting toxicities (DLTs)
10. Incidence and severity of adverse events (AEs)
11. Incidence and severity of changes in laboratory values
12. Incidence of antidrug antibodies (ADAs) to epcoritamab
13. PK parameters (clearance, volume of distribution, area under-the- concentration-time curve [AUC0-last and AUC0-∞], maximum concentration [Cmax], time of Cmax [Tmax], predose values, and halflife [t½])
14. Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genmab A/S

Sponsor organisation

Genmab A/S

Address

Kalvebod Brygge 43

City

Copenhagen V

Postcode

1560

Country

Denmark

Scientific contact point

Organisation

Genmab A/S

Contact name

Information

Public contact point

Organisation

Genmab A/S

Contact name

Information

Third parties 12

Locations

8 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 2 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 159 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications