Study of Safety and Antitumor Activity of GEN1056 in Participants With Advanced Solid Tumors

Solid Tumor, Adult Clinical Trial

Official title:

A First-in-Human, Open-label, Dose-finding Trial to Evaluate the Safety and Antitumor Activity of GEN1056 in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05586321
• Other study ID #: GCT1056-01
• Secondary ID: 2022-001003-40
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 24, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: April 2024
• Source: Genmab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this first-in-human study of GEN1056, is to evaluate safety. In addition, the study will determine the recommended dose and frequency for subsequent clinical studies and will assess the preliminary anti-tumor activity of GEN1056. GEN1056 will be studied in patients with advanced or metastatic solid cancer, for whom standard of care (SOC) therapy is not an option. All participants will get GEN1056.

Description:

The trial is a first-in-human open-label, dose-finding, multinational safety trial, in participants with advanced or metastatic solid (non central nervous system [CNS]) tumors that have exhausted SOC therapy or are not candidates for SOC therapy, evaluating the safety, tolerability, preliminary antitumor activity, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of GEN1056. The trial will be conducted as follows: - The Dose Escalation part (Part 1) will explore the safety of escalating doses of GEN1056 - The Dose schedule optimization part (Part 2) will explore further safety and tolerability in an alternate schedule of a dose based on data outcome available from Part 1.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 26
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Subjects with histologically or cytologically confirmed non-CNS advanced or metastatic solid tumors which has progressed despite standard therapy, or subjects who are intolerant of standard therapy, or for which no standard therapy exists, and for whom, in the opinion of the investigator, experimental therapy with GEN1056 may be beneficial
• Have personally (or in countries where permitted, their legally acceptable representative) signed an Informed Consent Form (ICF)
• Are at least 18 years of age.
• Have measurable disease according to the RECIST v1.1 criteria.
• Have an ECOG PS of 0 to 1 at screening and on C1D1 pre-treatment.
• Have acceptable laboratory test results during the screening period.
• Must provide an archival (FFPE) tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• A female subject with reproductive potential must agree to use adequate contraception during the trial, and for 4 months after receiving the last dose of trial drug GEN1056.

Key Exclusion Criteria:

• Subject is considered a poor medical risk due to a serious, uncontrolled inter-current illness
• Prior therapy with a checkpoint inhibitor agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
• Prior exposure to any of the following prior therapies within the specified

timeframes:

1. Systemic cytotoxic chemotherapy or antineoplastic biological therapy within 28 days or at least 5 elimination half-lives of the drug (whichever is shorter) of the first dose of trial treatment

2. Radiotherapy within 21 days of start of trial treatment. Note: palliative radiotherapy be allowed.

3. Prior treatment with live, attenuated vaccines within 28 days prior to initiation of GEN1056

• Known active CNS metastases and/or carcinomatous meningitis, or spinal cord compression.
• Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen (HBsAg), HBV DNA), or Hepatitis C infection (Hepatitis C Virus Ribonucleic Acid (HCV RNA), HCV antibodies).
• An active, known, or suspected autoimmune disease, requiring systemic steroid.
• A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.
• History of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease requiring treatment with steroids. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Biological:
• GEN1056
GEN1056 will be administered as an intravenous (IV) infusion. The dose levels will be determined by the starting dose and the escalation steps taken in the trial in Part 1. In Part 2, the dose and schedule will be decided based on data outcome from Part 1.

Locations

Country	Name	City	State
Georgia	ARENSIA Exploratory Medicine LLC	Tbilisi
Moldova, Republic of	ARENSIA Exploratory Medicine Phase I Unit	Chisinau
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Clinica Universidad de Navarra	Pamplona

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	BioNTech SE

Countries where clinical trial is conducted

Georgia,  Moldova, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT)	To define the maximum tolerated dose (MTD) and/or recommended phase 2 dose(s) (RP2D) of GEN1056	DLTs are evaluated during the first 21 days after a patient's first dose
Primary	Incidence and severity of adverse events (AEs)		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Primary	Number of participants with clinical significant shifts from baseline in clinical laboratory parameters	Clinical laboratory parameters assessed: Hematology, biochemistry, coagulation, TSH, T3 and T4, urinalysis	Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Objective response rate (ORR)	Anti-tumor activity of GEN1056 as monotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for responders (with confirmation)	From first infusion of trial drug to the last evaluable imaging assessment (an estimated average of 7 months)
Secondary	Duration of response (DOR)	Anti-tumor activity of GEN1056 as monotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for responders (with confirmation)	From initial onset of response to first progression event (defined as radiographic progression or death; an estimated average of 7 months)
Secondary	Progression-free survival (PFS)	Anti-tumor activity of GEN1056 as monotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	From first infusion of trial drug to first progression event (defined as radiographic progression or death; an estimated average of 7 months)
Secondary	Overall survival (OS)	Defined as time of death, due to any cause	From first infusion of trial drug to death due to any cause, or to last contact date in case of no observed death (assessed up to 2 years after the last participant's first dose in the trial)
Secondary	Rate at which the drug is removed from the body (clearance)		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Amount of drug in the body (volume of distribution)		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Area under the concentration time curve (AUC) from time zero to last quantifiable sample AUClast		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Maximum (peak) observed serum drug concentration (Cmax)		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Time to reach maximum (peak) serum drug concentration (Tmax) after dosing		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Time after dosing at which the lowest drug concentration is observed before the next dose is administered, predose trough concentration (Ctrough)		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Elimination half-life (T1/2) of the drug		Throughout the trial until the end of the safety follow-up period (90 days after last dose)
Secondary	Incidence of anti-drug antibodies (anti GEN1056 antibodies)	Characterize the immunogenicity of GEN1056	Throughout the trial until the end of the safety follow-up period (90 days after last dose)