Clinical trial NCT06771921: A First-in-Human Trial of Safety and Efficacy of GEN1078 in Participants With Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Solid Tumor
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2025-01-13
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: No randomization will be performed in the Dose-escalation part. In Dose-expansion part, if two expansion doses are identified, participants will be randomized to either Expansion Dose 1 or Expansion Dose 2.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 \&amp;gt;10 milligrams (mg) daily (or equivalent) or a cumulative dose \&amp;gt;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.

Primary outcomes:
measure: Dose Escalation: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Up to 21 days
measure: Dose Escalation: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose until the end of the safety follow-up period (30 days after the last dose)
measure: Dose Expansion: Confirmed Objective Response Rate (ORR)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Dose-Escalation and Expansion: Clearance (CL) of GEN1078
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Volume of Distribution (Vd) of GEN1078
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-last) of GEN1078
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC0-∞) of GEN1078
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Maximum Observed Plasma Concentration (Cmax) of GEN1078
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Time to Reach Cmax (Tmax) for GEN1078
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Predose Concentration for GEN1078
timeFrame: Predose up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Terminal Half-life (t½) of GEN1078
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 3 months)
measure: Dose-Escalation and Expansion: Number of Participants with Anti-drug Antibodies (ADAs)
timeFrame: Up to approximately 5 years
measure: Dose Escalation: Confirmed ORR
timeFrame: Up to approximately 5 years
measure: Dose-Escalation and Expansion: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Dose-Escalation and Expansion: Disease Control Rate (DCR)
timeFrame: Up to approximately 5 years
measure: Dose-Escalation and Expansion: Time to Response (TTR)
timeFrame: Up to approximately 5 years
measure: Dose Expansion: Number of Participants With AEs
timeFrame: From first dose until the end of the safety follow-up period (30 or 60 days after the last dose)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Righshospitalet (Copenhagen University Hospital)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitary Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: NEXT Oncology Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: