Trial to Assess the Safety and Preliminary Efficacy of GEN1055 on Malignant Solid Tumors as Monotherapy and as Combination Therapy

NCT06391775 | Terminated Phase 1 FDA Drug

• 2 other identifiers: GCT1055-012023-507049-28-00
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 4

Brief Summary

The goal of this trial is to learn about the antibody GEN1055 when it is used alone and when it is used together with another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of participants with certain types of cancer. Participants will receive either GEN1055 alone, GEN1055 with pembrolizumab, or GEN1055 with pembrolizumab and chemotherapy. All participants will receive active drug; no one will receive placebo. This trial has 2 parts. The purpose of the first part is to find out if GEN1055 is safe and to find out the doses of GEN1055 to use alone and to use with pembrolizumab. The purpose of the second part is to give GEN1055 to more participants to see how well the doses of GEN1055 that were selected in the first part work against cancer alone and how well they work with pembrolizumab (with or without other chemotherapy). A participant will receive trial treatment up to a maximum of 24 months for pembrolizumab-containing regimens, or until:

• the cancer progresses.
• there are side effects requiring that treatment be stopped.
• the participant decides to not participate further in this trial.
• the doctor believes it is in the participant's best interest to stop treatment. Participation in the trial will require visits to the site. For the first 12 weeks there will be weekly visits and after that, visits will be every 3 weeks. 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. The trial duration (including screening, treatment, and follow-up) for each participant will be about 39 months.

Conditions

Malignant Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Dose Escalation: Number of Participants With Adverse Events (AEs)

  From first dose date up to end of the survival follow up period (up to 39 months)

• Dose Escalation: Number of Participants With DLTs

  Toxicities will be graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.

  During first cycle (21 days) for each cohort

• Expansion: Overall Response Rate (ORR)

  ORR is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as assessed by investigator.

  Up to 39 months

Secondary Outcomes (15)

• Dose Escalation and Expansion: Maximum (peak) Plasma Concentration (Cmax) of GEN1055

  Predose and postdose at multiple timepoints of each Cycle up to end of treatment (Cycle length=21 days)

• Dose Escalation and Expansion: Time to Reach Cmax (Tmax) for GEN1055

  Predose and postdose at multiple timepoints of each Cycle up to end of treatment (Cycle length=21 days)

• Dose Escalation and Expansion: Plasma Trough (Pre-dose) Concentrations (Ctrough) of GEN1055

  Predose and postdose at multiple timepoints of each Cycle up to end of treatment (Cycle length=21 days)

• Dose Escalation and Expansion: Area Under the Concentration-Time Curve from Time 0 to Last Quantifiable Sample (AUC0-tlast) for GEN1055

  Predose and postdose at multiple timepoints of each Cycle up to end of treatment (Cycle length=21 days)

• Dose Escalation and Expansion: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-inf) for GEN1055

  Predose and postdose at multiple timepoints of each Cycle up to end of treatment (Cycle length=21 days)

Study Arms (2)

Dose Escalation

EXPERIMENTAL

GEN1055 will be administered as monotherapy and in combination with a fixed dose of pembrolizumab.

Biological: GEN1055; Biological: Pembrolizumab

Expansion

EXPERIMENTAL

GEN1055 will be administered as monotherapy or in combination with pembrolizumab or in combination with pembrolizumab and standard chemotherapy in separate expansion cohorts, at a dose level selected from the Dose Escalation part.

Biological: GEN1055; Biological: Pembrolizumab; Drug: Standard Chemotherapy

Interventions

GEN1055 BIOLOGICAL

Intravenous (IV) administration.

Dose Escalation; Expansion

Pembrolizumab BIOLOGICAL

IV administration

Dose Escalation; Expansion

Standard Chemotherapy DRUG

IV administration

Expansion

Eligibility Criteria

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

You may qualify if:

• All cohorts:
• Be at least 18 years of age.
• Have measurable disease according to RECIST v1.1.
• Provide all pre-baseline scans since failure of last prior therapy (ie, documented radiographic progressive disease \[PD\]), if available.
• Have Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1 at screening and on C1D1 pretreatment.
• Provide a biopsy (ie, formalin-fixed paraffin-embedded slides/block). A fresh biopsy taken during the screening period is preferred, unless medically unfeasible and after review and approval by the sponsor. If this cannot be provided, a biopsy taken after failure/stop of last prior treatment and taken within 6 months prior to C1D1 may be provided.
• Phase 1a and 1b- Dose Escalation:
• Have histologically or cytologically confirmed non-Central Nervous System (CNS) primary solid tumors who have metastatic or advanced disease.
• Have progressed on standard of care (SoC) therapy which should include platinum-based chemotherapy and anti-PD/PD-L1 therapies, 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 GEN1055 or GEN1055+pembrolizumab may be beneficial, in the opinion of the investigator.
• Phase 2a - Expansion:

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 (including coronavirus disease 2019 \[COVID-19\] infection).
• Significant cardiovascular impairment including:
• i) Symptomatic congestive heart failure (Class III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia.
• ii) Uncontrolled hypertension defined as systolic blood pressure ≥160-millimeter (mm) Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management.
• iii) Prolonged corrected QT interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula.
• Ongoing or recent (within 1 year of screening) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs).
• History of grade 3 or higher irAEs that led to treatment discontinuation of a checkpoint inhibitor (CPI). A participant with irAEs below grade 3 that led to discontinuation should be discussed with the sponsor. Grade 3 irAEs that have fully recovered may also be discussed.
• History of chronic liver disease (eg, alcoholic hepatitis or nonalcoholic steatohepatitis), drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis.
• Evidence of interstitial lung disease.
• Ongoing pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of noninfectious drug-, immune-, or radiation-related pneumonitis that has required steroids.
• Has been exposed to any of the following prior therapies/treatments within the specified timeframes:
• 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.
• 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.
• Has received granulocyte or granulocyte/macrophage colony-stimulating factor support within 2 weeks prior to first trial treatment administration or is chronically transfusion-dependent.

Sponsors & Collaborators

• Genmab: lead
• BioNTech SE: collaborator

Study Sites (4)

Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Hospital Universtari Val D´Hebron

Barcelona, Spain

Location

Start Madrid Ciocc Hm Sanchinarro

Madrid, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 30, 2024
• Study Start: May 14, 2024
• Primary Completion: November 20, 2025
• Study Completion: November 20, 2025
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); ES (3)