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

Phase 1/2

Active, not recruiting

• Conditions: Lymphoma of B-cell origin

• Registration Number: 2023-504802-12-00
• Lead Sponsor: Genmab A/S

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-02-07
• Last Update Posted: 2025-03-06

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 395

Inclusion Criteria

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. 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

Study & Design

• Study Type: Not specified
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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)		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)
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		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
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		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
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)		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)
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)		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)
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)		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)
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		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

Trial Locations

Locations (41)

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.; 🇮🇹 Meldola, Italy

Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo Alessandria; 🇮🇹 Alexandria, Italy

Ospedale San Raffaele S.r.l.; 🇮🇹 Milan, Italy

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico; 🇮🇹 Bologna, Italy

Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS; 🇮🇹 Candiolo, Italy

Pratia S.A.; 🇵🇱 Cracow, Poland

Wojewodzki Szpital Specjalistyczny Im. Janusza Korczaka W Slupsku Sp. z o.o.; 🇵🇱 Slupsk, Poland

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy; 🇵🇱 Warsaw, Poland

Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu; 🇵🇱 Wroclaw, Poland

SZPITAL NA KLINACH Grupa Neo Hospital; 🇵🇱 Kraków, Poland

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Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

🇮🇹Meldola, Italy

Gerardo Musuraca

Site contact

+390543739422

gerardo.musuraca@irst.emr.it