A first-in-human trial of safety and efficacy of GEN3017 in subjects with Hodgkin lymphoma or non-Hodgkin 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] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Immune System Diseases [C20]

Trial duration

completed 5 Feb 2025

Decision date (initial)

2023-11-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genmab A/S

External identifiers

EU CT number

2023-503348-15-00

ClinicalTrials.gov

NCT06018129

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Pharmacokinetic, Pharmacodynamic, Safety

Dose escalation:
1.Determine the maximum tolerated dose (MTD) and/or maximum administered dose (MAD) and recommended phase 2 dose (RP2D), or dose(s) to be studied in the expansion part

2.Evaluate the safety and tolerability of GEN3017

Expansion:
1.Assess the preliminary anti-tumor activity of GEN3017

Secondary objectives 6

1. Dose Escalation: Characterize the pharmacokinetic (PK) properties of GEN3017.
2. Dose Escalation: Evaluate immunogenicity.
3. Dose Escalation: Assess the preliminary anti-tumor activity of GEN3017
4. Expansion: Assess the anti-tumor activity and efficacy of GEN3017
5. Expansion: Evaluate safety and immunogenicity of GEN3017
6. Expansion: Characterize the PK of GEN3017

Conditions and MedDRA coding

Hodgkin lymphoma or non-Hodgkin lymphoma

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Dose Escalation: Must be at least 18 years of age. For subjects in the R/R cHL Cohort in the United States (US) and Australia, must be at least 16 years of age.
2. Histologically confirmed R/R cHL or R/R TCL.
3. Participants must have at least 1 measurable lesion by fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrating positive lesion compatible with computed tomography (CT)- or magnetic resonance imaging (MRI)-defined anatomical tumor sites and a CT scan (or MRI) with involvement of ≥1 measurable nodal lesion and/or ≥1 measurable extranodal lesion.
4. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 for participants 18 years of age and above. For participants ≥16 and <18 years of age (US and Australia only), Karnofsky score of >60% per Karnofsky performance scale.
5. Confirmed CD30-positivity in tumor biopsy prior to the first dose of GEN3017.
6. R/R cHL Cohort in Dose Escalation:• Must have relapsed or progressive cHL after receiving at least 2 or 3 prior lines of therapy. OR • Refractory to the second line of therapy

Exclusion criteria 8

1. Primary central nervous system (CNS) tumor or known CNS involvement.
2. Received prior investigational CD30-targeting therapy.
3. Autologous HSCT within 60 days prior to the first dose of GEN3017 or any prior allogeneic HSCT.
4. Chemotherapy within 2 weeks or major surgery within 4 weeks prior to the first dose of GEN3017.
5. Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks prior to the first dose of GEN3017.
6. Treatment with an investigational drug within 4 weeks or 5 half-lives of the drug, whichever is shorter prior to the first dose of GEN3017 or currently receiving any other investigational agents.
7. Prior treatment with live, attenuated vaccines within 30 days prior to the first dose of GEN3017.
8. Receiving immunosuppressive drugs or systemic corticosteroids such as prednisone at doses >25 mg daily or its equivalent within 14 days prior to the first dose of GEN3017. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose Escalation: Incidence of dose-limiting toxicities (DLTs)
2. Incidence and severity of adverse events (AEs)
3. Expansion: ORR based on the Lugano criteria as assessed by independent review committee (IRC)

Secondary endpoints 6

1. Dose Escalation: Noncompartmental PK parameters: • Maximum concentration (Cmax) • Time to Cmax (tmax) • Predose trough concentration (Ctrough) • Area under the concentration-time curve from time 0 to last quantifiable sample (AUClast) and from time 0 to infinity (AUCinf) • Elimination half-life (T1/2) • Clearance • Volume of distribution
2. Dose Escalation: Anti-GEN3017 antibodies
3. Dose Escalation: Anti-tumor activity based on the Lugano criteria as assessed by investigator: • Objective response rate (ORR) • Duration of response (DOR) • Time to response (TTR)
4. Expansion: Anti-tumor activity based on the Lugano criteria as assessed by IRC and investigator: • ORR (investigator only) • CR (complete response) rate • DOR • TTR • PFS (progression-free survival) • OS (overall survival)
5. Expansion: • Safety: Incidence and severity of AEs and serious adverse events (SAEs) • Immunogenicity: Anti-GEN3017 antibodies
6. Expansion: PK parameters (clearance; volume of distribution; AUClast; AUCinf; Cmax; Tmax; Ctrough; and t1/2)

Investigational products

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

Test 1

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 12

Locations

5 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

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

Application history

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