A Study of GEN1106 in Participants With Solid Tumors

Official title

First-In-Human, Open-Label, Dose Escalation and Expansion Trial to Evaluate the Safety, Pharmacokinetics and Efficacy of GEN1106 in Participants With Solid Tumors

Overview

The purpose of this trial is to learn about the safety and effectiveness of GEN1106 when it is used for the treatment of participants with certain types of cancer. The trial has multiple parts. The first part of the trial tests different doses of GEN1106 to find out if it is safe and determine what are the best doses to use. The second and third parts continues to test the safety of and how well GEN1106 works in additional participants with a specific cancer type and at doses chosen based on results from the first part of the trial. For each participant, the trial will last approximately 17 months but will vary for each person. This includes up to 21 days for screening prior to receiving trial treatment, approximately 5 months of treatment (the duration of treatment may vary for each participant), and approximately 11 months of follow up after trial treatment ends (the duration of follow up may vary for each participant). Participation in the trial will require visits to the site, with more frequent visits during the first 6 weeks of treatment and then less frequent visits afterwards. At site visits, there will be various tests (such as blood draws) and procedures (such as recording of heart activity, computed tomography \[CT\] scans) to monitor whether the treatment is safe and effective. All participants will receive active drug; no one will be given placebo.

Detailed description

This is a first-in-human (FIH), open-label, multicenter, dose escalation and expansion trial in participants with urothelial and other cancers who have metastatic disease to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of GEN1106.

Interventions

• Biological GEN1106
  Intravenous (IV) infusion.

Primary outcome measures

• Part 1 Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs) [Time frame: 21 days]
• Part 1 Dose Escalation: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Up to approximately 16 months]
• Part 2 Dose Refinement: Number of Participants with AEs and SAEs [Time frame: Up to approximately 16 months]
• Part 3 Expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Time frame: Up to approximately 16 months]

Secondary outcome measures (12)

• Part 1 Dose Escalation and Part 2 Dose Refinement: ORR per RECIST v1.1 [Time frame: Up to approximately 16 months]
• Part 3 Expansion: Number of Participants with AEs and SAEs [Time frame: Up to approximately 16 months]
• Part 1 Dose Escalation and Part 2 Dose Refinement: Number of Participants with Antidrug Antibodies (ADA) to GEN1106 [Time frame: Up to approximately 5 months]
• Part 3 Expansion: Number of Participants with ADA to GEN1106 [Time frame: Up to approximately 5 months]
• Part 1 Dose Escalation and Part 2 Dose Refinement: Plasma Concentrations of GEN1106-related Analytes [Time frame: Up to approximately 5 months]
• Part 3 Expansion: Plasma Concentrations of GEN1106-related Analytes [Time frame: Up to approximately 5 months]
• Part 1 Dose Escalation and Part 2 Dose Refinement: Disease Control Rate (DCR) per RECIST v1.1 [Time frame: Up to approximately 16 months]
• Part 3 Expansion: DCR per RECIST v1.1 [Time frame: Up to approximately 16 months]
• Part 1 Dose Escalation and Part 2 Dose Refinement: Duration of Response (DOR) per RECIST v1.1 [Time frame: Up to approximately 16 months]
• Part 3 Expansion: DOR per RECIST v1.1 [Time frame: Up to approximately 16 months]
• Part 1 Dose Escalation and Part 2 Dose Refinement: Time to Response (TTR) per RECIST v1.1 [Time frame: Up to approximately 16 months]
• Part 3 Expansion: TTR per RECIST v1.1 [Time frame: Up to approximately 16 months]

Eligibility criteria

Inclusion criteria

• Have progressed on or after standard of care (SoC) therapy, which should include chemotherapy, anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapies, and enfortumab vedotin (EV), if applicable for the tumor type, or for whom there is no available standard therapy likely to provide clinical benefit, and for whom experimental therapy with GEN1106 may be beneficial, in the opinion of the investigator.
• Have measurable disease according to RECIST v1.1.
• Have Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1 at screening.
• Part 1: Have histologically or cytologically confirmed diagnosis of cancer as specified per protocol.
• Parts 2 and 3: Have histologically or cytologically confirmed diagnosis of metastatic urothelial carcinoma (mUC).

Exclusion criteria

• Prior treatment with topoisomerase 1 inhibitor-based antibody-drug conjugate (ADC) therapy.
• Treatment with an anticancer agent within 4 weeks or for systemic therapies within 5 half-lives of the drug, whichever is shorter, prior to trial treatment administration.
• Has clinically significant toxicities from previous anticancer therapies that have not resolved to baseline levels or to grade 1 or lower, except for alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy must have recovered to grade 2.

Note: Other protocol-defined Inclusion and Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• Yale Cancer Center — New Haven
• START New York Long Island LLC — Lake Success
• Carolina Urologic Research Center — Myrtle Beach
• South Texas Accelerated Research Therapeutics — San Antonio

Spain · 3 centers

• START Madrid - Hospital Universitario Fundacion Jimenez Diaz — Madrid
• START Madrid - Centro Integral Oncologico Clara Campal — Madrid
• Hospital Universitario Quironsalud Madrid — Madrid

Japan · 1 center

• National Cancer Center Hospital — Chuo Ku

Identifiers

NCT: NCT07416123 · GCT1106-01 · 2025-523760-21-00 · jRCT2031260042

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗