Clinical trial NCT06573294: Trial to Assess the Safety and Antitumor Activity of GEN1057 in Malignant Solid Tumors
Official title: A First-In-Human, Open-Label, Dose Escalation Trial to Evaluate the Safety and Antitumor Activity of GEN1057 in Subjects With Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Malignant Solid Tumor
Metastatic Malignant Solid Tumor
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2024-08-27
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to study the antibody GEN1057 when used as a single agent for the treatment of certain types of cancer.

Trial details include:

* The trial duration will be up to approximately 11 months.
* The treatment duration will be up to approximately 4 months (the duration of treatment may vary for each participant) and the follow-up duration will be approximately 6 months.

Participation in the trial will require visits to the site. All participants will receive active drug; no one will be given placebo.

Detailed description: The trial is a first-in-human (FIH) open-label, multicenter, multinational safety trial.

The dose escalation will evaluate different dose levels by assessing safety, tolerability, and early efficacy signals to determine the expansion dose(s) of GEN1057 as monotherapy, as well as characterizing the pharmacokinetic (PK) profile and immunogenicity in participants with malignant solid tumors who have metastatic or advanced disease.

Eligibility criteria: Key Inclusion Criteria:

* Advanced and/or metastatic malignant solid tumors, who have progressed on standard of care therapy for whom there is no available standard therapy likely to provide clinical benefit, or who are not candidates for available therapy, and for whom experimental therapy with GEN1057 may be beneficial, in the opinion of the investigator.
* Be at least 18 (or the legal age of consent in the jurisdiction in which the trial is taking place) years of age.
* Have measurable disease according to RECIST v1.1.
* Have Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 at screening and on C1D1 pretreatment. Note: If screening ECOG PS is assessed within 3 days prior to C1D1, ECOG PS does not need to be reassessed at C1D1.
* Have a life expectancy of ≥3 months.

Key Exclusion Criteria:

* Has been exposed to any of the following prior therapies/treatments within the specified timeframes:

  * Treatment with an investigational anticancer agent within 28 days or for systemic therapies within 5 half-lives of the drug, whichever is shorter, prior to trial treatment administration.
  * Treatment with an investigational drug, including investigational vaccines within 28 days before the planned first dose of trial treatment.
  * Prior treatment with live, attenuated vaccines within 28 days prior to initiation of GEN1057. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live, attenuated vaccines and are not allowed. Experimental and/or nonauthorized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations are not allowed.
  * Used an invasive investigational medical device within 28 days before the planned first dose of trial treatment.
* Has clinically significant toxicities from previous anticancer therapies that have not resolved to baseline levels or to grade 1, except for anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to ≤ grade 2. There is no limitation for alopecia and hearing impairment from previous therapies.
* Has known, symptomatic brain metastases. Asymptomatic brain metastases are allowed provided that they have been treated, have been stable for \>28 days as documented by radiographic imaging, and do not require prolonged (\>14 days) systemic corticosteroid therapy.
* Has a past or current malignancy other than inclusion diagnosis.

Note: Other protocol-defined inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (AEs)
timeFrame: From first dose until the end of the safety follow-up period (approximately 5 months)
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 21 days
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of GEN1057
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 4 months)
measure: Time to Reach Cmax (Tmax) of GEN1057
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 4 months)
measure: Trough Concentrations (Ctrough) of GEN1057
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 4 months)
measure: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUC0-last) of GEN1057
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 4 months)
measure: AUC From Time Zero to Infinity (AUC0-inf) of GEN1057
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 4 months)
measure: Half-life (t1/2) of GEN1057
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 4 months)
measure: Clearance (CL) of GEN1057 From Plasma
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 4 months)
measure: Number of Participants with Anti-drug Antibodies (ADAs) to GEN1057
timeFrame: Up to approximately 11 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 11 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 11 months
measure: Time to Response (TTR)
timeFrame: Up to approximately 11 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 11 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Tokyo
country: Japan
facility: National Cancer Center, Tsukiji 5-1-1
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Start Madrid Centro Integral Oncologico Clara Campal CIOCC
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: