A Phase 1/2, Open-Label, Dose-Escalation Trial of GEN3013 in Patients with Relapsed, Progressive or Refractory B-Cell Lymphoma

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 May 2018 → ongoing

Decision date (initial)

2024-02-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Genmab A/S

External identifiers

EU CT number

2023-504802-12-00

EudraCT number

2017-001748-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Dose response, Efficacy, Safety

Escalation Phase:
- Determine maximum tolerated dose and recommended phase 2 dose
Expansion Phase:
- To evaluate clinical efficacy as determined by Lugano criteria
Optimization part:
- to determine whether an alternative priming/intermediate dose
regimen may reduce CRS risk

Secondary objectives 2

1. Escalation Phase: -Establish tolerability of epcoritamab -Establish PK profile after single and multiple doses -Evaluate immunogenicity -Evaluate anti-lymphoma activity
2. Expansion and Optimization Part: -To further evaluate clinical efficacy as determined by Lugano criteria -To evaluate clinical efficacy as determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) -To further evaluate clinical efficacy -To evaluate MRD status as a clinical efficacy endpoint -To evaluate safety and tolerability of epcoritamab -To evaluate the PK and immunogenicity of epcoritamab -To evaluate patient-reported outcomes (PROs) related to lymphoma symptoms -To evaluate safety and tolerability of alternative priming/intermediate dosing regimens

Conditions and MedDRA coding

Lymphoma of B-cell origin

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Federal Agency For Medicines And Health Products, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Patient must be 18 years of age or older (for expansion: In countries where the legal age is 21 years of age; only patients 21 years of age or older are eligible) 2. Documented CD20+ mature non-Hodgkin B-cell lymphoma according to WHO classification 3. Relapsed, progressive and/or refractory disease (Cheson et al., 2007) following treatment with an anti-CD20 monoclonal antibody 4. Patients must have received at least 2 prior lines of therapy 5. Patients must have measurable disease by imaging 6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. For MCL: ECOG PS <2 required for participation. 7. For the optimization part, patients must have R/R DLBCL, or FL grades 1-3A, or MCL (according to cohort).

Exclusion criteria 1

1. 1. Primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma 2. AST, and/or ALT > 3 x upper limit of normal 3. Total bilirubin > 1.5 x upper limit of normal 4. Creatinine clearance < 45 mL/min 5. Known clinically significant cardiac disease, including: a. Onset of unstable angina pectoris within 6 months of signing ICF b. Acute myocardial infarction within 6 months of signing ICF c. Congestive heart failure (grade III or IV as classified by the New York Heart Association and/or known decrease ejection fraction of < 45% 6. Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrolment or within the previous 2 weeks prior to the first dose of epcoritamab, including COVID-19 infection. 7. Eligible for curative salvage therapy with high dose therapy followed by stem cell rescue 8. Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR positive infection). Subjects with evidence of prior HBV but who are PCRnegative are permitted in the trial but should receive prophylactic antiviral therapy. 9. Known human immunodeficiency virus (HIV) infection. 10. Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF 11. Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first GEN3013 administration 12. Autologous HSCT within 100 days prior to first GEN3013 administration, or any prior allogeneic HSCT or solid organ transplantation 13. Contraindication to all uric acid lowering agents

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Escalation End Points: - Dose limiting toxicity - Adverse events
2. Expansion End Points: - Overall response rate (ORR) determined by Lugano criteria as assessed by independent review committee (IRC)
3. Optimization End Points: - Adverse events; Rating of ≥ Grade 2 CRS events

Secondary endpoints 7

1. Escalation End Points: - Cytokine measures - Laboratory parameters (biochemistry, hematology including immunophenotyping for absolute T-cell and B-cell counts as well as Tcell activation and exhaustion markers) - PK parameters (clearance, volume of distribution and area-under-the concentration- time curve (AUC0-Clast and AUC0-∞), maximum concentration (Cmax), time of Cmax (Tmax), pre dose values, and halflife)
2. Escalation End Points: - Immunogenicity of GEN3013 - Anti-lymphoma activity, i.e. resolution of constitutional symptoms, reduction in tumor size, objective and best response - Duration of response - Progression free survival - Time to next anti-lymphoma therapy - Overall survival
3. Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Duration of response (DOR) determined by Lugano criteria - Complete response (CR) rate determined by Lugano criteria - Duration of CR (DoCR) by Lugano criteria - Progression-free survival (PFS) determined by Lugano criteria - Time to response (TTR) determined by Lugano criteria
4. Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Objective and best response rate determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) - PFS determined by LYRIC - DOR determined by LYRIC - DoCR determined by LYRIC - TTR determined by LYRIC - Overall survival (OS)
5. Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Time to next (anti-lymphoma) therapy (TTNT) - Rate of MRD negativity - Safety (i.e., adverse events, laboratory parameters, hospitalizations, and cytokine measures)
6. Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - PK parameters (clearance, volume of distribution, Cmax, Tmax, trough concentrations, and half-life) and incidence of ADAs to GEN3013 - Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym)
7. Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Rate of ≥ Grade 2 CRS events and all grade CRS events following first full dose Rate of ≥ Grade 2 CRS events and all grade CRS events overall

Investigational products

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

Test 2

Auxiliary 7

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

Clinical Trial Information

Public contact point

Organisation

Genmab A/S

Contact name

Clinical Trial Information

Third parties 13

Locations

9 EU/EEA countries · 41 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 75 files

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

Application history

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