GEN1047 for Solid Tumors - First in Human (FIH) Trial

• ClinicalTrials.gov Identifier: NCT05180474
• Recruitment Status: Recruiting
• First Posted: January 6, 2022
• Last Update Posted: May 7, 2024
• Sponsor: Genmab
• Information provided by (Responsible Party): Genmab

Tracking Information

• First Submitted Date: November 8, 2021
• First Posted Date: January 6, 2022
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: December 13, 2021
• Estimated Primary Completion Date: January 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2023)

• Escalation: Number of Participants with Dose Limiting Toxicities [ Time Frame: From the first Cycle (Cycle length=21 days) in each cohort ]
  To determine the maximum tolerated dose (MTD) and/or maximum administered dose (MAD) and recommended phase 2 dose (RP2D) or doses, to be studied in expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
• Escalation: Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From first dose date up to end of the safety follow up period, 30 days after last dose ]
  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAE is defined as an AE occurring or worsening between the first dose of study drug and 30 days after the last dose received.
• Expansion: Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
  ORR is defined as percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1.

Original Primary Outcome Measures (submitted: December 17, 2021)

• Escalation: Dose Limiting Toxicities (DLTs) [ Time Frame: DLTs are evaluated during the first cycle (21 days) in each cohort ]
  To evaluate the safety of GEN1047 and determine the recommended phase 2 dose
• Escalation: Adverse Events (AEs) [ Time Frame: Throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  To evaluate the safety and tolerability of GEN1047 throughout the treatment period of trial participants
• Escalation: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Clinical laboratory parameters assessed: Hematology, biochemistry, coagulation, urinalysis, hepatitis B, T3 and T4, CA-125 (Cancer-antigen 125; only participants with ovarian cancer)
• Expansion: Evaluate anti-tumor activity of GEN1047 [ Time Frame: Response assessment will be evaluated through trial completion, up to 5 years after the first visit of the last participant ]
  Reduction in tumor size according to response assessment (Objective Response Rate)

Current Secondary Outcome Measures (submitted: April 19, 2023)

• Escalation and Expansion: Clearance [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) ]
• Escalation and Expansion: Volume of Distribution (Vd) [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) ]
• Escalation and Expansion: Area Under the Concentration-time Curve from Time 0 to Time of Last Dose (AUClast) [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) ]
• Escalation and Expansion: Maximum (Peak) Plasma Concentration (Cmax) [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) ]
• Escalation and Expansion: Time to Reach Cmax (Tmax) [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) ]
• Escalation and Expansion: Plasma Trough (Pre-dose) Concentrations (Cthrough) [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) ]
• Escalation and Expansion: Elimination half-life (t 1/2) [ Time Frame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) ]
• Escalation and Expansion: Number of Participants with Anti-Drug Antibody (ADA) [ Time Frame: Up to 5 years ]
• Escalation: ORR [ Time Frame: Up to 5 years ]
  ORR is defined as percentage of participants with BOR of confirmed CR or confirmed PR based on RECIST v1.1.
• Escalation and Expansion: Duration of Response (DOR) [ Time Frame: Up to 5 years ]
  DOR is defined as the time from the first documented response to the first documented progression or death due to any cause.
• Escalation and Expansion: Time to response (TTR) [ Time Frame: Up to 5 years ]
  Time to response (TTR) is defined as the time from the date of Cycle 1 Day 1 (C1D1) to the first documented response of either confirmed CR or confirmed PR.
• Escalation and Expansion: Disease control rate (DCR) [ Time Frame: Up to 5 years ]
  The disease control rate (DCR) is defined as the percentage of participants with BOR of confirmed CR, confirmed PR, or SD according to RECIST v1.1
• Expansion: Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
  PFS is defined as the time from the date of C1D1 to the date of the first documented progression or death due to any cause, whichever occurs earlier according to RECIST v1.1.
• Expansion: Overall Survival (OS) [ Time Frame: Up to 5 years ]
  OS is defined as the time from date of C1D1 to date of death due to any cause.
• Expansion: Number of Participants with TEAEs [ Time Frame: From first dose date up to end of the safety follow up period, 30 days after last dose ]
  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAE is defined as an AE occurring or worsening between the first dose of study drug and 30 days after the last dose received.

Original Secondary Outcome Measures (submitted: December 17, 2021)

• Escalation and expansion: To characterize the pharmacokinetic (PK) properties of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Rate at which the drug is removed from the body (clearance)
• Escalation and expansion: To characterize the PK properties of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Amount of drug in the body (volume of distribution)
• Escalation and expansion: To characterize the PK properties of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Area-under-the-concentration-time curve (AUC0-C last) and from time 0 to last quantifiable sample (AUC0-C infinity)
• Escalation and expansion: To characterize the PK properties of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Maximum (peak) concentration (Cmax) after dosing
• Escalation and expansion: To characterize the PK properties of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Time after dosing at which Cmax was observed (Tmax)
• Escalation and expansion: To characterize the PK properties of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Time after dosing at which the lowest drug concentration is observed before the next dose is administered, pre-dose trough concentration (CTrough)
• Escalation and expansion: To characterize the PK properties of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Elimination half-life of the drug (T1/2)
• Escalation and expansion: Evaluate immunogenicity of GEN1047 [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Anti-drug antibody response (ADA)
• Escalation: Evaluate anti-tumor activity of GEN1047 [ Time Frame: Response assessment will be evaluated through trial completion, up to 5 years after the first visit of the last participant ]
  Reduction in tumor size according to response assessment (Objective Response Rate)
• Escalation and expansion: Evaluate preliminary anti-tumor activity of GEN1047 (efficacy) [ Time Frame: Response assessment will be evaluated through trial completion, up to 5 years after the first visit of the last participant ]
  Disease control rate (DCR)
• Escalation and expansion: Evaluate preliminary anti-tumor activity of GEN1047 (efficacy) [ Time Frame: Response assessment will be evaluated through trial completion, up to 5 years after the first visit of the last participant ]
  Duration of response (DOR)
• Escalation and expansion: Evaluate preliminary anti-tumor activity of GEN1047 (efficacy) [ Time Frame: Response assessment will be evaluated through trial completion, up to 5 years after the first visit of the last participant ]
  Time to response (TTR)
• Expansion: Evaluate preliminary efficacy of GEN1047 [ Time Frame: Response assessment will be evaluated through trial completion, up to 5 years after the first visit of the last participant ]
  Progression free survival (PFS)
• Expansion: Evaluate preliminary efficacy of GEN1047 [ Time Frame: Survival will be monitored from first dose of GEN1047 until death, up to 5 years after the first visit of the last participant ]
  Overall survival (OS)
• Expansion: AEs [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  To evaluate the safety and tolerability of GEN1047 throughout the treatment period of trial participants
• Expansion: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters [ Time Frame: Collected throughout the trial until the end of the safety follow-up period (30 days after last dose) ]
  Clinical laboratory parameters assessed: Hematology, biochemistry, coagulation, urinalysis, hepatitis B, T3 and T4, CA-125 (only participants with ovarian cancer)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GEN1047 for Solid Tumors - First in Human (FIH) Trial
• Official Title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1047 in Subjects With Malignant Solid Tumors
• Brief Summary: The drug investigated in the study is an antibody, GEN1047. Since this is the first study of GEN1047 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN1047 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN1047. GEN1047 will be studied in a broad group of cancer participants, having different kinds of solid tumors. All participants will get GEN1047. The study consists of two parts: Part 1 tests increasing doses of GEN1047 ("escalation"), followed by Part 2 ("expansion") which tests the recommended GEN1047 dose from Part 1.
• Detailed Description: The trial is an open-label, multi-center safety trial of GEN1047. The trial consists of two parts: a dose escalation part ("escalation" - phase 1) and an expansion part ("expansion" - phase 2a). The goal of the dose escalation part is to find out if GEN1047 is safe in participants with specific solid tumors and to find the best dose(s). In the expansion part of the trial up to two doses of GEN1047 will be tested.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer, Breast Neoplasms
• Endometrial Cancer, Endometrial Neoplasm
• Ovarian Cancer, Ovarian Neoplasms
• Squamous Non Small Cell Lung Cancer (NSCLC-SCC)

Intervention

Biological: GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive cells.

GEN1047 will be administered as an intravenous infusion. The dose-levels will be determined by the starting dose and the escalation steps taken in the trial.

Study Arms

Experimental: GEN1047

Intervention: Biological: GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive cells.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 19, 2023): 500
• Original Estimated Enrollment (submitted: December 17, 2021): 220
• Estimated Study Completion Date: June 30, 2026
• Estimated Primary Completion Date: January 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

Criteria - Escalation Part:

• Participant must have histologically or cytologically confirmed solid tumor(s) in any of the following selected indications 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 GEN1047 may be beneficial (breast cancer, endometrial cancer, ovarian cancer, squamous non-small-cell lung cancer [NSCLC-SCC]).
• Participants with ovarian cancer must have documented progressive disease (PD) on or after last prior treatment and within 60 days of screening.
• Must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) on the day of signing informed consent.
• Must have either recurrence after, or progression on or lack of response to available relevant standard of care (SoC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting.
• Must have at least 1 measurable lesion per RECIST v1.1. The measurable lesion(s) must be outside the field of radiation therapy (RT) if there was prior treatment with RT.
• Must have an Eastern Cooperative Oncology Group performance status (ECOGPS) score of 0 to 1 at Screening and on C1D1 pretreatment.
• Should provide a tumor tissue sample during the Screening period and prior to C1D1.
• Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.

Criteria - Expansion Part:

• Participants must have documented PD according to RECIST v1.1 on or after last prior treatment with latest scan performed a maximum of 28 days prior to the first dose.
• Participant must have advanced (unresectable) or metastatic, histologically confirmed diagnosis (breast cancer, endometrial cancer, ovarian cancer.
• Must be a female and at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) at the time of consent.
• Must have at least 1 measurable lesion per RECIST v1.1 as assessed by local investigator.
• Must have an ECOG- PS score of 0 to 1 at Screening and on Cycle 1 Day 1 (C1D1) pretreatment.
• Should provide a tumor tissue sample during the Screening period and prior to C1D1.
• Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.

Key Exclusion Criteria:

• Significant cardiovascular impairment within 6 months of the first dose of trial drug.
• Participant with new or progressive brain metastases or spinal cord compression.
• Participant has a history of bowel obstruction related to underlying disease.
• Participant has been exposed to any prior therapy with a compound targeting CD3 and/or B7H4 or cell based therapies.
• Current pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of non-infectious drug-, immune-, or radiation-related pneumonitis that required steroid.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Genmab Trial Information; +4570202728; clinicaltrials@genmab.com

• Listed Location Countries: Belgium, Denmark, France, Italy, Netherlands, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05180474
• Other Study ID Numbers: GCT1047-01; 2021-001790-23 ( EudraCT Number ); 2024-510722-10-00 ( Registry Identifier: EU CTIS )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Genmab
• Original Responsible Party: Same as current
• Current Study Sponsor: Genmab
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Genmab
• Verification Date: May 2024