Clinical trial NCT06018129: A First-in-human Trial of GEN3017 in Hodgkin Lymphoma and Non-Hodgkin Lymphoma
Official title: A Phase 1/2a, Open-Label, Dose Escalation Trial of GEN3017 With Expansion Cohorts in Relapsed or Refractory CD30+ Classical Hodgkin Lymphoma and CD30+ Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Classical Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2023-08-30
Enrollment: 9
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of GEN3017 as a monotherapy in participants with relapsed or refractory (R/R) CD30-expressing lymphomas.

GEN3017 will be administered via subcutaneous injections.

All participants will receive active drug; no one will be given placebo.

Detailed description: This multicenter trial will be conducted in 2 parts: Dose Escalation (phase 1) and Expansion (phase 2a).

The Dose Escalation Part (phase 1) of the trial will evaluate dose-limiting toxicities (DLTs) to determine the recommended phase 2 dose (RP2D), and if reached, the maximum tolerated dose (MTD) for R/R CD30+ classical Hodgkin lymphoma (cHL) and R/R CD30+ T-cell lymphoma (TCL), respectively.

The Expansion Part (phase 2a) will evaluate the anti-tumor activity of GEN3017 at the RP2D and selected dosage(s) will be assessed together with safety, immunogenicity, pharmacokinetics, and pharmacodynamics in R/R CD30+ cHL participants (including adults; and adolescent and young adults) and in participants with selected R/R CD30+ TCL subtypes (adults only).

Eligibility criteria: Key Inclusion Criteria:

Dose Escalation Part:

1. Must be at least 18 years of age. For participants 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:

   * 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.

Key Exclusion Criteria:

1. Primary central nervous system (CNS) tumor or known CNS involvement.
2. Received prior investigational CD30-targeting therapy (except brentuximab vedotin).
3. Autologous hematopoietic stem cell transplant (HSCT) within 60 days (applies to both cHL and TCL). Allogeneic HSCT within 90 days (applies to cHL) prior to the first dose of GEN3017.
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 milligrams (mg) daily or its equivalent within 14 days prior to the first dose of GEN3017.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Dose Escalation Part: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: During the first cycle (Cycle length = 21 days)
measure: Dose Escalation Part: Number of Participants with Adverse Events (AEs)
timeFrame: From baseline up to 60 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years)
measure: Expansion Part: Objective Response Rate (ORR)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Dose Escalation and Expansion Part: Maximum (Peak) Plasma Concentration (Cmax) of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length =21 days)
measure: Dose Escalation and Expansion Part: Time to Reach Cmax (Tmax) of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Pre-dose (Trough) concentration (Ctrough) of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Elimination Half-life (T1/2) of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Total Body Clearance (CL) of Drug From Plasma of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Volume of distribution (Vd) of GEN3017
timeFrame: Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Number of Participants with Anti-drug Antibodies (ADA) to GEN3017
timeFrame: Predose at multiple timepoints of each cycle up to end of treatment (Cycle length = 21 days)
measure: Dose Escalation and Expansion Part: Objective Response Rate (ORR)
timeFrame: Up to 5 years
measure: Dose Escalation and Expansion Part: Duration of Response (DOR)
timeFrame: Up to 5 years
measure: Dose Escalation and Expansion Part: Time to Response (TTR)
timeFrame: Up to 5 years
measure: Expansion Part: Complete Response Rate (CRR)
timeFrame: Up to 5 years
measure: Expansion Part: Progression Free Survival (PFS)
timeFrame: Up to 5 years
measure: Expansion Part: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Expansion Part: Number of Participants with AEs and Serious Adverse Events (SAEs)
timeFrame: From first dose until the end of the safety follow-up period (60 days after last dose) up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Helford Clinical Research Hospital
state: California
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute trading as Peter MacCallum Cancer Centre
state: Victoria
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: