Back to resultsA First-in-human Trial of GEN3017 in Hodgkin Lymphoma and Non-Hodgkin Lymphoma
Primary Purpose
Classical Hodgkin Lymphoma, Non-Hodgkin Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GEN3017
Sponsored by
About this trial
This is an interventional treatment trial for Classical Hodgkin Lymphoma
Eligibility Criteria
Key Inclusion Criteria: Dose Escalation Part: 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. Histologically confirmed R/R cHL or R/R TCL. 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. 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. Confirmed CD30-positivity in tumor biopsy prior to the first dose of GEN3017. 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: Primary central nervous system (CNS) tumor or known CNS involvement. Received prior investigational CD30-targeting therapy. Autologous hematopoietic stem cell transplant (HSCT) within 60 days prior to the first dose of GEN3017 or any prior allogeneic HSCT. Chemotherapy within 2 weeks or major surgery within 4 weeks prior to the first dose of GEN3017. Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks prior to the first dose of GEN3017. 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. Prior treatment with live, attenuated vaccines within 30 days prior to the first dose of GEN3017. 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.
Sites / Locations
- City of HopeRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
R/R CD30+ cHL Cohort
R/R CD30+ TCL Cohort
Arm Description
Outcomes
Primary Outcome Measures
Dose Escalation Part: Number of Participants with Dose Limiting Toxicities (DLTs)
All AEs including DLTs will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version (v) 5.0 unless otherwise specified. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be evaluated according to the American society for transplantation and cellular therapy (ASTCT) criteria. Clinical tumor lysis syndrome (CTLS) will be evaluated according to the Cairo-Bishop classification.
Dose Escalation Part: Number of Participants with Adverse Events (AEs)
Expansion Part: Objective Response Rate (ORR)
The ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Lugano criteria assessed by an independent review committee (IRC).
Secondary Outcome Measures
Dose Escalation and Expansion Part: Maximum (Peak) Plasma Concentration (Cmax) of GEN3017
Dose Escalation and Expansion Part: Time to Reach Cmax (Tmax) of GEN3017
Dose Escalation and Expansion Part: Pre-dose (Trough) concentration (Ctrough) of GEN3017
Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of GEN3017
Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) of GEN3017
Dose Escalation and Expansion Part: Elimination Half-life (T1/2) of GEN3017
Dose Escalation and Expansion Part: Total Body Clearance (CL) of Drug From Plasma of GEN3017
Dose Escalation and Expansion Part: Volume of distribution (Vd) of GEN3017
Dose Escalation and Expansion Part: Number of Participants with Anti-drug Antibodies (ADA) to GEN3017
Serum samples will be screened for ADAs binding to GEN3017 and the titer of confirmed positive samples will be reported.
Dose Escalation and Expansion Part: Objective Response Rate (ORR)
The ORR is defined as the percentage of participants with a BOR of CR or PR per Lugano criteria based on investigator assessment.
Dose Escalation and Expansion Part: Duration of Response (DOR)
DOR is defined as the time from the first documentation of response (CR or PR) to the date of progressive disease or death, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment (expansion only).
Dose Escalation and Expansion Part: Time to Response (TTR)
TTR is defined as the time from Cycle 1 Day 1 to first documentation of objective response in participants achieving PR or CR per Lugano criteria based on investigator and IRC assessment (expansion only).
Expansion Part: Complete Response Rate (CRR)
CRR is defined as the number of participants with CR per Lugano criteria based on investigator and IRC assessment.
Expansion Part: Progression Free Survival (PFS)
PFS is defined as the time from Cycle 1 Day 1 to first documented progressive disease or death due to any cause, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment.
Expansion Part: Overall Survival (OS)
OS is defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Expansion Part: Number of Participants with AEs and Serious Adverse Events (SAEs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06018129
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 21, 2023 (Actual)
Primary Completion Date
December 31, 2027 (Anticipated)
Study Completion Date
June 30, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genmab
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Classical Hodgkin Lymphoma, Non-Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
240 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
R/R CD30+ cHL Cohort
Arm Type
Experimental
Arm Title
R/R CD30+ TCL Cohort
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
GEN3017
Other Intervention Name(s)
DuoBody® CD3xCD30
Intervention Description
Subcutaneous injection
Primary Outcome Measure Information:
Title
Dose Escalation Part: Number of Participants with Dose Limiting Toxicities (DLTs)
Description
All AEs including DLTs will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version (v) 5.0 unless otherwise specified. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be evaluated according to the American society for transplantation and cellular therapy (ASTCT) criteria. Clinical tumor lysis syndrome (CTLS) will be evaluated according to the Cairo-Bishop classification.
Time Frame
During the first cycle (Cycle length = 21 days)
Title
Dose Escalation Part: Number of Participants with Adverse Events (AEs)
Time Frame
From baseline up to 30 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years)
Title
Expansion Part: Objective Response Rate (ORR)
Description
The ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Lugano criteria assessed by an independent review committee (IRC).
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Dose Escalation and Expansion Part: Maximum (Peak) Plasma Concentration (Cmax) of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length =21 days)
Title
Dose Escalation and Expansion Part: Time to Reach Cmax (Tmax) of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Pre-dose (Trough) concentration (Ctrough) of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Elimination Half-life (T1/2) of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Total Body Clearance (CL) of Drug From Plasma of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Volume of distribution (Vd) of GEN3017
Time Frame
Predose and postdose at multiple timepoints at end of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Number of Participants with Anti-drug Antibodies (ADA) to GEN3017
Description
Serum samples will be screened for ADAs binding to GEN3017 and the titer of confirmed positive samples will be reported.
Time Frame
Predose at multiple timepoints of each cycle up to end of treatment (Cycle length = 21 days)
Title
Dose Escalation and Expansion Part: Objective Response Rate (ORR)
Description
The ORR is defined as the percentage of participants with a BOR of CR or PR per Lugano criteria based on investigator assessment.
Time Frame
Up to 5 years
Title
Dose Escalation and Expansion Part: Duration of Response (DOR)
Description
DOR is defined as the time from the first documentation of response (CR or PR) to the date of progressive disease or death, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment (expansion only).
Time Frame
Up to 5 years
Title
Dose Escalation and Expansion Part: Time to Response (TTR)
Description
TTR is defined as the time from Cycle 1 Day 1 to first documentation of objective response in participants achieving PR or CR per Lugano criteria based on investigator and IRC assessment (expansion only).
Time Frame
Up to 5 years
Title
Expansion Part: Complete Response Rate (CRR)
Description
CRR is defined as the number of participants with CR per Lugano criteria based on investigator and IRC assessment.
Time Frame
Up to 5 years
Title
Expansion Part: Progression Free Survival (PFS)
Description
PFS is defined as the time from Cycle 1 Day 1 to first documented progressive disease or death due to any cause, whichever occurs earlier per Lugano criteria based on investigator and IRC assessment.
Time Frame
Up to 5 years
Title
Expansion Part: Overall Survival (OS)
Description
OS is defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Time Frame
Up to 5 years
Title
Expansion Part: Number of Participants with AEs and Serious Adverse Events (SAEs)
Time Frame
From first dose until the end of the safety follow-up period (30 days after last dose) up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Dose Escalation Part:
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.
Histologically confirmed R/R cHL or R/R TCL.
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.
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.
Confirmed CD30-positivity in tumor biopsy prior to the first dose of GEN3017.
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:
Primary central nervous system (CNS) tumor or known CNS involvement.
Received prior investigational CD30-targeting therapy.
Autologous hematopoietic stem cell transplant (HSCT) within 60 days prior to the first dose of GEN3017 or any prior allogeneic HSCT.
Chemotherapy within 2 weeks or major surgery within 4 weeks prior to the first dose of GEN3017.
Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks prior to the first dose of GEN3017.
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.
Prior treatment with live, attenuated vaccines within 30 days prior to the first dose of GEN3017.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Genmab Trial Information
Phone
+4570202728
Email
clinicaltrials@genmab.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Official
Organizational Affiliation
Genmab
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A First-in-human Trial of GEN3017 in Hodgkin Lymphoma and Non-Hodgkin Lymphoma
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