A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy

NCT05435339 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: GCT1053-012021-006692-4210057002022-502419-12-00
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 5

Brief Summary

The drug that will be investigated in the study is GEN1053. GEN1053 is an antibody designed to (re)activate and increase antitumor immunity. Since this is the first study of GEN1053 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN1053 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN1053. GEN1053 will be studied in a broad group of cancer patients, having different kinds of solid tumors. All participants will get GEN1053. The study consists of two parts: Part 1 tests increasing doses of GEN1053 ("escalation"), followed by Part 2 which tests the recommended phase 2 dose GEN1053 dose from Part 1 ("expansion").

Conditions

Solid Tumor, Adult

Keywords

Monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  The occurrence of any of the following toxicities, assessed as related to trial treatment, were considered DLTs: All Grade 5 events, Grade 4 anaphylaxis, infusion-related reactions and neutropenia for ≥7 days, Grade 3/4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 4 anemia, Grade 4 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin elevation/Grade 3 that did not recover to ≤Grade 1 within 14 days, AST or ALT elevations ≥Grade 2 with concomitant bilirubin \>2.0×upper limit of normal with no signs of cholestasis, any Grade 4 immune-related adverse event (irAE), Grade 3 irAEs that did not improve to ≤Grade 1 within 7 days (with exceptions), Grade 4 cytokine release syndrome (CRS), Grade 3 CRS not resolved to ≤Grade 2 within 48 hrs following adequate intervention, any other ≥Grade 3 nonhematological adverse event (AE) during the first GEN1053 treatment cycle (with exceptions), cycle=3 weeks.

  Day 1 up to Day 21

• Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)

  An adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal safety laboratory parameter finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE was defined as an AE occurring or worsening after first dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

  Up to approximately 1.5 years

Secondary Outcomes (12)

• Clearance (CL) of GEN1053

  Cycle 1 and Cycle 3 (cycles were 3 weeks)

• Volume of Distribution (Vz) of GEN1053

  Cycle 1 and Cycle 3 (cycles were 3 weeks)

• Maximum (Peak) Concentration (Cmax) of GEN1053

  Cycle 1 and Cycle 3 (cycles were 3 weeks)

• Time to Maximum (Peak) Concentration (Tmax) of GEN1053

  Cycle 1 and Cycle 3 (cycles were 3 weeks)

• Predose Trough Concentration (Ctrough) of GEN1053

  Cycle 1 and Cycle 3 (cycles were 3 weeks)

Study Arms (1)

GEN1053 Monotherapy

EXPERIMENTAL

Biological: GEN1053

Interventions

GEN1053 BIOLOGICAL

GEN1053 will be administered as an intravenous (IV) infusion every 3rd week. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.

GEN1053 Monotherapy

Eligibility Criteria

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

You may qualify if:

• For both the Dose Escalation and Expansion parts:
• Be ≥18 years of age.
• Have measurable disease according to RECIST 1.1
• Provide all pre-baseline scans since failure of last prior therapy (ie radiographic PD), if available
• Have Eastern Cooperative Oncology Group performance status ≤1.
• Have organ and bone marrow function as follows:
• Bone marrow / hematological function:
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L
• Hemoglobin ≥9.0 g/dL
• Platelet count ≥150×10\^9/L
• Liver function:
• Total bilirubin ≤ upper limit of normal (ULN)
• Alanine aminotransferase ≤1.5×ULN
• Aspartate aminotransferase ≤1.5×ULN
• Albumin ≥30 g/L

You may not qualify if:

• Has uncontrolled intercurrent illness, including but not limited to:
• Ongoing or active infection requiring IV treatment with anti-infective therapy administered less than 2 weeks prior to first dose.
• 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 mm Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management.
• Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula.
• Ongoing or recent (within 1 year) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.
• History of grade 3 or higher irAEs that led to treatment discontinuation of a CPI.
• History of chronic liver disease or evidence of hepatic cirrhosis.
• Evidence of interstitial lung disease.
• Ongoing pneumonitis or history of non-infectious pneumonitis that has required steroids.
• Known platelet function defects
• Prior therapy:
• Radiotherapy within 14 days prior to first GEN1053 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 GEN1053 administration.
• Subject with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal or pituitary replacement steroid \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Sponsors & Collaborators

• Genmab: lead
• BioNTech SE: collaborator

Study Sites (5)

Yale University

New Haven, Connecticut, 06510, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, Spain

Location

Related Links

• Results Summary in Plain Language

Results Point of Contact

• Title: CLINICAL TRIAL INFORMATION
• Organization: Genmab

clinicaltrials@genmab.com

+45 7020 2728

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Model Details: Sequential assignment

Study Record Dates

• First Submitted: June 23, 2022
• First Posted: June 28, 2022
• Study Start: October 4, 2022
• Primary Completion: May 24, 2024
• Study Completion: May 24, 2024
• Last Updated: April 22, 2025
• Results First Posted: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); US (2)