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

NCT ID: NCT04424641

Last Updated: 2023-07-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-15
• Study Completion Date: 2021-10-29

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.

Detailed Description

The trial is an open-label, multi-center safety trial of GEN1044. The trial consists of two parts: a dose-escalation part (Phase 1) and an expansion part (Phase 2a). The expansion part of the trial will be initiated once the RP2D has been determined from Phase 1.

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

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GEN1044

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

GEN1044 will be administered intravenously in cycles of 21 days.

Interventions

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

GEN1044 will be administered intravenously in cycles of 21 days.

Intervention Type: BIOLOGICAL

Other Intervention Names

DuoBody®-CD3x5T4

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

1. Has an uncontrolled intercurrent illness, including but not limited to:

1. Ongoing or active infection requiring intravenous treatment with anti-infective therapy

2. Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.

3. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.

4. 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.

5. Patients with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.

6. History of chronic liver disease or evidence of hepatic cirrhosis.

7. History of non-infectious pneumonitis that has required steroids, or currently has pneumonitis.

8. 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.

9. Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.

2. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke.

3. Prior therapy:

Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed.

4. 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.

5. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Genmab

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Oliveri, MD

Role: STUDY_DIRECTOR

Genmab

Locations

Tennesse Oncology, PLLC - Nashville

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Rigshospitalet (Copenhagen University Hospital)

Copenhagen, , Denmark

Chaim Sheba Medical Center

Ramat Gan, , Israel

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Fundacion Jimenez Diaz

Madrid, , Spain

Countries

United States; Denmark; Israel; Spain

References

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.

Reference Type: BACKGROUND

PMID: 36271507 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-003998-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOH_2020-07-26_008713

Identifier Type: REGISTRY

Identifier Source: secondary_id

GCT1044-01

Identifier Type: -

Identifier Source: org_study_id