A Phase 3 Trial of Epcoritamab vs Investigator’s Choice Chemotherapy in R/R DLBCL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Dec 2020 → ongoing

Decision date (initial)

2024-02-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Genmab

External identifiers

EU CT number

2023-504830-23-00

EudraCT number

2020-003016-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy

Compare the clinical efficacy of epcoritamab to standard of care (SOC)(R-GemOx or BR)

Secondary objectives 4

1. Compare other measures of epcoritamab efficacy to SOC
2. Compare safety and tolerability of epcoritamab to SOC
3. Evaluate immunogenicity
4. To compare patient-reported outcomes (PROs) related to lymphoma symptoms between epcoritamab and SOC

Conditions and MedDRA coding

B-cell Lymphoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Must be at least 18 years of age
2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤3 times the upper limit of normal (x ULN), unless enzyme elevation is due to a nonhepatic origin or lymphoma involvement of the liver and ALT and AST levels are ≤5 xULN
3. Total bilirubin level ≤2 x ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin or lymphoma involvement of the liver and total bilirubin is ≤5xULN
4. Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 as calculated by Cockcroft-Gault
5. PT/INR/aPTT ≤1.5 xULN, unless receiving anticoagulation
6. A female subject with reproductive potential must agree to use adequate contraception during the trial, and for 12 months after the last administration of trial treatment. Adequate contraception is defined as highly effective methods of contraception
7. A female subject of childbearing potential must have a negative serum (beta-hCG) pregnancy test at screening and a negative serum or urine pregnancy test before treatment administration on Day 1 of every cycle
8. A male subject who is sexually active with a female of reproductive potential and has not had a vasectomy must agree to use a barrier method of birth control and (ie, condom) must agree not to donate sperm during the trial and for 12 months after receiving the last administration of trial treatment.
9. Life expectancy >2 months on SOC treatment.
10. Subject must sign an ICF indicating that the purpose of the trial and the procedures required for the trial are understood, and indicating that the subject is willing to participate in the trial prior to initiating any other trial-related assessments or procedures
11. ECOG PS score of 0-2
12. One of the confirmed histologies below wiht CD20 positivity: a. DLBCL, NOS (according to the WHO 2016 classification), and including de novo or histologically transformed from follicular lymphoma (FL). b. "Double-hit" or "triple-hit" DLBCL (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and / or BCL6 translocations), including de novo or histologically transformed from FL c. FL Grade 3B d. T-cell/histiocyte-rich large B-cell lymphoma
13. CD20-positivity at representative tumor biopsy based on the pathology report;
14. Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 mAbcontaining combination chemotherapy since lymphoma diagnosis (ie,having received R-CHOP or an equivalent regimen that would be considered adequate first-line treatment for DLBCL);
15. Failed previous HDT-ASCT or not eligible for HDT-ASCT at screening. If ineligible for HDT-ASCT, the decision must have been based on age, performance status, comorbidity, and/or insufficient response to prior treatment;
16. Has measurable disease: a. A fluorodeoxyglucose-positron emission tomography (FDG- PET) scan demonstrating positive lesion(s) compatible with computed tomography (CT) or magnetic resoncance imagining (MRI)-defined anatomical tumor sites b. ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) and/or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on CT scan or MRI;
17. Absolute neutrophil count ≥1.0 x 10e9/L (growth factor permitted)
18. Platelet count >75 x 10e9/L (or >50 x 10e9/L if bone marrow involvement or splenomegaly)
19. A female subject must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 12 months after the last administration of trial treatment

Exclusion criteria 26

1. Primary central nervous system (CNS) tumor or known CNS involvement as assessed by brain MRI at screening or by CT and lumbar puncture (if MRI contraindicated)
2. Seizure disorder requiring anti-epileptic therapy
3. Vaccination with live vaccines within 28 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever,rabies, Bacillus Calmette–Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Experimental and/or non authorized severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccinations are not allowed
4. Clinically significant cardiovascular disease
5. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec
6. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
7. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment at time of randomization
8. Known history of seropositivity for human immunodeficiency virus (HIV) infection. Note: HIV testing is required at screening only if required per local health authorities or institutional standards
9. Active hepatitis B virus (HBV) (DNA polymerase chain reaction [PCR]-positive) or hepatitis C (RNA PCR-positive infection). Subjects with evidence of prior HBV but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy. Subjects who received treatment for hepatitis C that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable
10. Has known past or current malignancy other than inclusion diagnosis, except for: a. Cervical carcinoma of Stage 1B or less b. Non-invasive basal cell or squamous cell skin carcinoma c. Non-invasive, superficial bladder cancer d. Prostate cancer with a current PSA level <0.1 ng/mL e. Any curable cancer with a complete response of >2 years duration
11. Contraindication to all uric acid lowering agents
12. Any prior therapy with a bispecific antibody targeting CD3 and CD20
13. A woman of childbearing potential with a positive serum or urine pregnancy test at screening. Female subjects must also agree not to breastfeed during the entire trial and until 12 months after the last administration of study drug
14. Clinically significant liver disease, including active hepatitis, current alcohol abuse, or cirrhosis
15. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
16. Receiving immunostimulatory agent
17. Prior allogeneic hematopoietic stem cell transplantation
18. History of severe allergic or anaphylactic reactions to anti-CD20 antibody therapy
19. Contraindication to any component of SOC regimen selected prior to randomization
20. Major surgery within 4 weeks prior to randomization
21. Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization
22. ASCT within 100 days of randomization
23. Treatment with CAR-T therapy within 100 days prior to randomization
24. Receiving immunosuppressive therapy, including more than the equivalent of ≥20 mg of prednisolone daily, unless for control of lymphoma or intermittent prophylaxis/treatment of allergic reactions
25. Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization
26. Has known or suspected allergies, hypersensitivity, or intolerance to epcoritamab or its excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall survival (OS)
2. Progression-free survival (PFS) determined by Lugano criteria per independent review committee (IRC) assessment

Secondary endpoints 17

1. Progression-free survival (PFS) determined by Lugano criteria per investigator assessment
2. Overall response rate (ORR) determined by Lugano criteria per IRC assessment and investigator assessment
3. Complete response (CR) rate determined by Lugano criteria per IRC assessment and investigator assessment
4. Duration of response (DOR) determined by Lugano criteria per IRC assessment and investigator assessment
5. Time to response (TTR) determined by Lugano criteria per IRC assessment and investigator
6. Rate and duration of minimal residual disease (MRD) negative status
7. PFS determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) per IRC assessment
8. ORR determined by LYRIC per IRC assessment
9. CR rate determined by LYRIC per IRC assessment
10. DOR determined by LYRIC per IRC assessment
11. TTR determined by LYRIC per IRC assessment
12. Time to next anti-lymphoma therapy (TTNT)
13. Incidence and severity of adverse events (AEs)
14. Incidence and severity of changes in laboratory values
15. Incidence of dose interruptions and delays
16. Anti-epcoritamab antibody response
17. 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 2

Comparator 4

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

Trial Information

Public contact point

Organisation

Genmab A/S

Contact name

Trial Information

Third parties 16

Locations

13 EU/EEA countries · 91 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 172 files

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

Application history

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