First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas

NCT04358458 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: GCT3009-012019-002752-16NL72025.056.20
• Study Type: interventional
• Target: 46
• Locations: 5 countries
• Sites: 17

Brief Summary

The drug that will be investigated in the study is an antibody, GEN3009. Since this is the first study of GEN3009 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN3009 dose to be tested in a larger group of patients and assess preliminary clinical activity of GEN3009. GEN3009 will be studied in a broad group of cancer patients, having different kinds of lymphomas. All patients will get GEN3009 either as a single treatment (monotherapy) or in combination with another antibody-candidate for treatment of cancer in the blood. The study consists of two parts: Part 1 tests increasing doses of GEN3009 ("escalation"), followed by Part 2 which tests the recommended GEN3009 dose from Part 1 ("expansion").

Conditions

Diffuse Large B-cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma; Mantle Cell Lymphoma; Chronic Lymphocytic Leukemia; High-grade B-cell Lymphoma; Primary Mediastinal Large B-cell Lymphoma

Keywords

Anti-CD37, monoclonal antibodies, DuoHexabody®

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLTs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, except for TLS (Cairo-Bishop grading) and CRS/ICANS (Lee et al., 2019). These criteria include: all Grade 5 toxicities; hematologic events including thrombocytopenia Grade 4, neutropenia Grade 4, Febrile neutropenia Grade 3 or 4, Grade 3 or 4 hemorrhage associated with thrombocytopenia of ≥Grade 3, anemia of Grade 4 and tumor lysis syndrome (TLS) Grade 4; and non-hematologic AEs of Grade 3 or higher excluding certain fevers, hypotension, laboratory values, Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), nausea, vomiting, diarrhea, fatigue/asthenia, or alopecia (no grading), which meet certain additional criteria.

  During the first treatment cycle (Cycle length=28 days)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as an AE that meets one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is "medically significant"\]); required inpatient hospitalization or prolongation of existing hospitalization. TEAEs are defined as AEs which begin, or worsen, during the on-treatment period ending 4 weeks after the last dose of study medication.

  From first dose until 30 days after the last dose (up to 15.5 months)

• Number of Participants With AEs of Special Interest (AESI)

  AESIs are defined as events (serious or non-serious) that are of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate.

  From first dose until 30 days after the last dose (up to 15.5 months)

• Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs

  Laboratory parameters included hematology, serum chemistries and urinalysis. Clinically significant laboratory abnormalities were based upon the Investigator's discretion. Laboratory parameters captured as AEs are reported in this outcome measure.

  From first dose until 30 days after the last dose (up to 15.5 months)

• Number of Participants With Clinically Notable Vital Signs

  Criteria for clinically notable (elevated and below normal values respectively) vital signs are as follows: Systolic Blood Pressure (SBP): ≥180 millimeters of mercury (mmHg) and an increase ≥20 mmHg from baseline, ≤90 mmHg and a decrease ≥20 mmHg from baseline; Diastolic Blood Pressure (DBP): ≥105 mmHg and an increase ≥15 mmHg from baseline, ≤50 mmHg and a decrease ≥15 mmHg from baseline; Heart rate: ≥120 beats per minute (bpm) with an increase of ≥15 bpm from baseline, ≤50 bpm and a decrease ≥15 bpm from baseline; Temperature: \> 38 degree Celsius (°C) and \< 35°C. Number of participants with clinically notable elevated and below normal vital signs values up to end of treatment are reported.

  From first dose up to end of treatment (up to 14.5 months)

• Number of Participants With Dose Delays and Dose Interruptions

  Number of participants with dose delays and dose Interruptions due to AE, Coronavirus disease 2019 (COVID-19), drug administration issues and other unspecified reasons are reported.

  From first dose until 30 days after the last dose (up to 15.5 months)

• Actual Dose Intensity

  Actual dose intensity (milligrams per cycle \[mg/cycle\]) is calculated as cumulative dose/number of cycles initiated.

  From first dose until 30 days after the last dose (up to 15.5 months)

Secondary Outcomes (16)

• Apparent Total Plasma Clearance (CL) of GEN3009

  Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2 hours (h) and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)

• Volume of Distribution of GEN3009

  Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)

• Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009

  Pre-dose and 5 minutes post-dose on days 1, 2 and 4 (S2 only); 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)

• AUC From Time 0 to Infinity (AUCinf) of GEN3009

  Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)

• AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009

  Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)

Study Arms (2)

Monotherapy Arm

EXPERIMENTAL

Biological: GEN3009

Combination Arm

EXPERIMENTAL

Biological: GEN3009; Biological: Epcoritamab

Interventions

GEN3009 BIOLOGICAL

GEN3009 will be administered by intravenous (IV) infusion in cycles of 28 days

Also known as: DuoHexaBody®-CD37

Combination Arm; Monotherapy Arm

Epcoritamab BIOLOGICAL

Epcoritamab will be administered by subcutaneous (SC) injections in cycles of 28 days

Also known as: DuoBody®-CD3xCD20, GEN3013, EPKINLY™

Combination Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be at least 18 years of age.
• Must sign an informed consent form prior to any screening procedures.
• Dose Escalation: Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, the experimental therapy may be beneficial. All subjects must have received at least two prior lines of systemic therapy.
• Dose Expansion: Has histologically or cytologically confirmed relapsed or refractory B-cell NHL. All subjects must have received at least 2 prior lines of systemic therapy, and,
• For FL and DLBCL, at least 1 of the 2 prior lines of treatment must have been a CD20 containing systemic regimen;
• For CLL, subjects must have received at least one prior line of BTK inhibitor or BCL 2 inhibitor.
• Has one of the eligible subtypes of B-cell NHL :
• Dose Escalation: (DLBCL, HGBCL, PMBCL, FL, MCL, MZL, SLL, or CLL). Dose Expansion: (DLBCL, FL, CLL)
• Has measurable disease for B-cell NHL or has active disease for Chronic Lymphocytic Leukemia (CLL).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Has adequate hepatic, renal, and bone marrow functions.
• Before the first dose of GEN3009, during the trial, and for 12 months after the last dose of GEN3009 and/or the combination, a woman must be either not of childbearing potential or of childbearing potential and practicing a highly effective method of birth control, and must have a negative serum beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test at screening.
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
• Subjects must have a life expectancy of at least 3 months.

You may not qualify if:

• Prior treatment with a CD37-targeting agent.
• Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
• Prior treatment with a CD3xCD20 bispecific antibody (Combination Expansion cohort only).
• Autologous HSCT within 3 months before the first dose of GEN3009.
• Lymphomas leukemic phase: high absolute lymphocyte count or the presence of abnormal cells in the peripheral blood indicating circulating lymphoma cells.
• Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009. Treatment with small molecules such as BTK inhibitors, BCL2 inhibitors, or PI3K inhibitors within 5 half-lives prior to the first dose of GEN3009.
• Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009.
• Treatment with an investigational drug or an invasive investigational medical device within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3009, and at any time during the study treatment period.
• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of prednisone within the 2-week period before the first dose of GEN3009.
• Has uncontrolled intercurrent illness.
• Seizure disorder requiring therapy (such as steroids or anti-epileptics) (Combination Expansion cohort only).
• Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
• Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.
• Had allergic reactions to anti-CD20 or anti-CD37 monoclonal antibody treatment or intolerant to GEN3009 or to the combination therapy excipients.

Sponsors & Collaborators

• Genmab: lead

Study Sites (17)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98133, United States

Location

UZ Leuven

Leuven, Belgium

Location

Rigshospitalet

Copenhagen, Denmark

Location

Odense Universitetshospital

Odense, Denmark

Location

Vejle Sygehus

Vejle, Denmark

Location

Amsterdam UMC, Locatie VUMC

Amsterdam, Netherlands

Location

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The trial was terminated due to strategic evaluation of GEN3009 within context of Genmab's portfolio, decision not based on any safety or regulatory concerns.

Results Point of Contact

• Title: CLINICAL TRIAL INFORMATION
• Organization: Genmab

clinicaltrials@genmab.com

+45 7020 2728

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 24, 2020
• Study Start: March 13, 2020
• Primary Completion: November 21, 2022
• Study Completion: July 28, 2023
• Last Updated: October 24, 2024
• Results First Posted: August 13, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); DK (3); NL (1); ES (5); BE (1)