A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Patients With Malignant Solid Tumors

NCT04424641 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: GCT1044-012019-003998-26MOH_2020-07-26_008713
• Study Type: interventional
• Target: 48
• Locations: 4 countries
• Sites: 6

Brief Summary

The purpose of the trial is to evaluate the safety, determine the recommended Phase 2 dose (RP2D), and assess preliminary clinical activity of GEN1044 in patients with solid tumors.

Conditions

Locally Advanced or Metastatic Solid Tumor(s); Prostate Cancer; Esophageal Cancer; Triple Negative Breast Cancer (TNBC); Squamous Cell Carcinoma of Head and Neck (SCCHN); Non-small Cell Lung Cancer (NSCLC); Bladder Cancer; Uterine Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  The DLT was defined as Grade (G) \>= 3 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; any G3 or 4 hematologic and non-hematologic toxicity (with exceptions defined by the protocol); laboratory abnormality that required clinically significant medical intervention, led to hospitalization, persisted for \>1 week, or resulted in a drug-induced liver injury; G3 or 4 febrile neutropenia; liver toxicity defined by Hy's law; any treatment-related toxicity that caused treatment discontinuation during Cycle 1; or any G5 toxicity.

  From Day 1 to Day 21 of first cycle

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

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; 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. A TEAE is defined as an AE occurring or worsening between the first dose of GEN1044 and 30 days after the last dose received.

  Day 1 through Day 263 (corresponding to maximum observed duration)

• Number of Participants With Abnormal Laboratory Values

  Number of participants with laboratory values of Grade \>= 3 by NCI-CTCAE v5.0 are reported. The NCI-CTCAE is a descriptive terminology that is used for gradings (Grade 1-5) of Adverse Events (AEs) and of laboratory values; the latter being summarized here. This table reports laboratory values graded only on the numerical value of the reported parameter and is therefore not graded by symptoms or signs. The abnormal laboratory values assessed by the investigator as being AEs are reported also in the AE table. In case a participant reported multiple severity grades for a laboratory value, only the maximum grade was used.

  Day 1 through Day 263 (corresponding to maximum observed duration)

Secondary Outcomes (2)

• Number of Participants With Complete Response (CR) or Partial Response (PR)

  Day 1 through Day 233

• Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044

  Day 1 through Day 263 (predose on Day 1 of Cycles 1, 2, 3, 5, 7, and then on Day 1 of every 4 cycles thereafter, end of treatment [EOT], and 30 days after last study drug)

Study Arms (1)

GEN1044

EXPERIMENTAL

Biological: GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4.

Interventions

GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4. BIOLOGICAL

GEN1044 will be administered intravenously in cycles of 21 days.

Also known as: DuoBody®-CD3x5T4

GEN1044

Eligibility Criteria

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

You may qualify if:

• Dose-escalation part:
• Patient with locally advanced or metastatic solid tumor(s) (excluding patients with primary central nervous system \[CNS\] tumors), who has experienced disease progression while on standard therapy or is intolerant of, or not eligible for, standard therapy.
• Expansion part:
• Must have an advanced or metastatic, pathologically confirmed diagnosis of one of the following tumors: Uterine Cancer, Prostate Cancer, Esophageal Cancer, TNBC, SCCHN, NSCLC (both adenocarcinoma \[ACC\] and squamous cell carcinoma \[SCC\], Bladder Cancer.
• Both parts:
• Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the trial, and is willing to participate in the trial prior to any trial related assessments or procedures.
• Must have measurable disease according to response assessment criteria relevant to the tumor type.
• Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1.
• A woman of reproductive potential must agree to use adequate contraception during the trial and for 4 months after the last GEN1044 administration. Adequate contraception is defined as highly effective methods of contraception.

You may not qualify if:

• Has an uncontrolled intercurrent illness, including but not limited to:
• Ongoing or active infection requiring intravenous treatment with anti-infective therapy
• Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
• Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.
• Ongoing or recent evidence of significant autoimmune disease. Patients with a history of grade 3 or higher immune-related adverse events that led to treatment discontinuation.
• Patients with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
• History of chronic liver disease or evidence of hepatic cirrhosis.
• History of non-infectious pneumonitis that has required steroids, or currently has pneumonitis.
• History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1044.
• Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
• Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke.
• Prior therapy:
• Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed.
• Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved.
• Has a history of ≥ grade 2 cytokine release syndrome (CRS) with other CD3-based bispecifics, or a history of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or has known allergies, hypersensitivity, or intolerance to GEN1044 or its excipients.

Sponsors & Collaborators

• Genmab: lead
• AbbVie: collaborator

Study Sites (6)

Tennesse Oncology, PLLC - Nashville

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77054, United States

Location

Rigshospitalet (Copenhagen University Hospital)

Copenhagen, 2100, Denmark

Location

Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Related Publications (1)

• Kemper K, Gielen E, Boross P, Houtkamp M, Plantinga TS, de Poot SA, Burm SM, Janmaat ML, Koopman LA, van den Brink EN, Rademaker R, Verzijl D, Engelberts PJ, Satijn D, Sasser AK, Breij EC. Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models. Life Sci Alliance. 2022 Sep 8;5(11):e202201481. doi: 10.26508/lsa.202201481. Print 2022 Nov.

  PMID: 36271507 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms; Esophageal Neoplasms; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Urinary Bladder Neoplasms; Uterine Neoplasms

Interventions

Immunoglobulin G

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urinary Bladder Diseases; Urologic Diseases; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Upon review and evaluation of the overall safety profile and safety signals of GEN1044 during the dose-escalation part, the Safety Committee decided to stop further enrollment and the Sponsor decided to stop the compound development. Hence, the expansion part of the trial was never initiated, and while a majority of the pharmacokinetic (PK) samples from the dose-escalation part were quantified, the PK parameters were not calculated due to termination of the trial.

Results Point of Contact

• Title: Clinical Trial Information
• Organization: Genmab

clinicaltrials@genmab.com

+45 7020 2728

Study Officials

• Roberto Oliveri, MD

  Genmab

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 14, 2020
• First Posted: June 11, 2020
• Study Start: July 15, 2020
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: July 25, 2023
• Results First Posted: February 1, 2023

Record last verified: 2023-07

Locations

ES (2); IL (1); DK (1); US (2)