A First-in-Human Trial of Safety and Efficacy of GEN1078 in Participants With Solid Tumors

First-in-Human, Open-Label, Dose-Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of GEN1078 in Subjects With Malignant Solid Tumors

The purpose of this trial is to measure the following in participants with solid cancers who receive GEN1078.

• The side effects seen with GEN1078
• What the body does with GEN1078 once it is administered
• What GEN1078 does to the body once it is administered
• How well GEN1078 works against advanced solid tumors

Trial details include:

• The estimated trial duration is 8 months for an individual participant (the trial duration may vary for each participant).
• The treatment duration will be an estimated 3-month treatment period (the duration of treatment may vary for each participant).
• The visit frequency will be daily or visits every few days for the first few months.

All participants will receive active drug; no one will be given placebo.

Study Overview

• Status: Terminated
• Conditions: Malignant Solid Tumor
• Intervention / Treatment: Drug: GEN1078

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Righshospitalet (Copenhagen University Hospital)
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain
    • Next Oncology Madrid
  • Madrid, Spain
    • Hospital Universitary Fundacion Jimenez Diaz
  • Pamplona, Spain
    • Clinica Universidad de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must have at least 1 measurable lesion per RECIST v1.1 assessed by the investigator.
• Must have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1.

Dose Escalation Only

• Participant must have histologically or cytologically confirmed solid tumor(s) for which there is no further available standard therapy likely to confer clinical benefit (or participant is not a candidate or has previously refused such earlier available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1078 may be beneficial.
• Must have either recurrence after, or progression on available relevant standard of care (SoC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting.

Expansion Only

• Participant must have advanced (unresectable) or metastatic, histologically confirmed diagnosis of selected solid cancers.

Key Exclusion Criteria:

• Has significant cardiovascular impairment within 6 months prior to the first dose of trial drug, including presence of unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] class III and IV), or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
• Known unstable central nervous system (CNS) metastases or any active or history of carcinomatous meningitis.

• Has been exposed to any of the following prior therapies within the specified timeframes:

  • Prior therapy with a compound targeting the same targets as GEN1078 or any cell-based therapies.
  • Radiotherapy within 14 days prior to C1D1. Palliative radiotherapy of bone metastases up to 7 days prior to C1D1 will be allowed.
  • Treatment with any investigational or non-investigational anticancer agent (including investigational vaccines) or used an invasive investigational medical device within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the first dose of GEN1078.
  • Chemotherapy within 2 weeks prior to the first dose of GEN1078.
  • Prophylaxis with live, attenuated vaccines within 28 days prior to first dose of GEN1078; or prophylaxis with the first and/or subsequent injection(s) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid vaccine within 14 days prior to first dose of GEN1078.
  • Chronic systemic immunosuppressive treatment, including corticosteroids, ie, prednisone >10 milligrams (mg) daily (or equivalent) or a cumulative dose >140 mg prednisone within 14 days (or equivalent) before the first dose of GEN1078. Replacement therapy (eg, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
  • Has received granulocyte colony-stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within 2 weeks prior to the first dose GEN1078 or being chronically transfusion dependent.
  • Has received other T-cell activating surface marker. Note: Prior treatment with anti-T-cell Ig and ITIM domain (aTIGIT), anti-programmed cell death protein 1 (aPD1), anti-programmed death-ligand 1 (aPDL1), anti-lymphocyte activation gene 3 protein (aLAG3), anti-cytotoxic T-lymphocyte-associated protein 4 (aCTLA-4) is allowed.
  • The initiation of growth factors and bisphosphonates is not allowed during the first 4 weeks of GEN1078 administration, unless agreed upon by the investigator and sponsor medical monitor. However, the use of receptor activator of nuclear factor kappa-Β ligand (RANK-L) inhibitors and bisphosphonates (if on stable dose for at least 4 weeks) is permitted while participating in this trial.

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-Escalation; GEN1078 will be administered as monotherapy until one of the treatment discontinuation criteria has been met.	Drug: GEN1078; Specified dose on specified days.
Experimental: Dose Expansion; GEN1078 will be administered as monotherapy until one of the treatment discontinuation criteria has been met.	Drug: GEN1078; Specified dose on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Number of Participants With Dose-limiting Toxicities (DLTs)	Toxicities will be graded for severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0, except for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) which will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.	Up to 21 days
Dose Escalation: Number of Participants With Adverse Events (AEs)		From first dose until the end of the safety follow-up period (30 days after the last dose)
Dose Expansion: Confirmed Objective Response Rate (ORR)	Confirmed ORR is defined as the percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on response evaluation criteria in solid tumors (RECIST) v1.1 as assessed by the investigator.	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Escalation and Expansion: Clearance (CL) of GEN1078		Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Volume of Distribution (Vd) of GEN1078		Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-last) of GEN1078		Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC0-∞) of GEN1078		Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Maximum Observed Plasma Concentration (Cmax) of GEN1078		Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Time to Reach Cmax (Tmax) for GEN1078		Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Predose Concentration for GEN1078		Predose up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Terminal Half-life (t½) of GEN1078		Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
Dose-Escalation and Expansion: Number of Participants with Anti-drug Antibodies (ADAs)		Up to approximately 5 years
Dose Escalation: Confirmed ORR	Confirmed ORR is defined as the percentage of participants with confirmed BOR of CR or PR based on RECIST v1.1 as assessed by the investigator.	Up to approximately 5 years
Dose-Escalation and Expansion: Duration of Response (DOR)	DOR is defined as the time from first documentation of response (CR or PR) to the date of the first documented progression or death whichever occurs earlier based on RECIST v1.1 as assessed by the investigator.	Up to approximately 5 years
Dose-Escalation and Expansion: Disease Control Rate (DCR)	The DCR is defined as the percentage of participants with confirmed BOR of CR, PR, or Stable Disease (SD) according to RECIST v1.1 as assessed by investigator.	Up to approximately 5 years
Dose-Escalation and Expansion: Time to Response (TTR)	TTR based on investigator assessment is defined as the time from Cycle 1, Day 1 (C1D1) to first documentation of objective response (CR or PR) in participants achieving PR or CR according to RECIST v1.1 as assessed by investigator.	Up to approximately 5 years
Dose Expansion: Number of Participants With AEs		From first dose until the end of the safety follow-up period (30 or 60 days after the last dose)

Collaborators and Investigators

• Sponsor: Genmab
• Investigators: Study Director: Study Official, Genmab

Publications and helpful links

Helpful Links

• Results Summary in Plain Language

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2025
• Primary Completion (Actual): June 11, 2025
• Study Completion (Actual): June 11, 2025

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): January 13, 2025

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GCT1078-01; 2024-515752-21-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No