Clinical trial NCT06685068: A Phase 1/2 Study of GEN1286 in Patients With Advanced Solid Tumors
Official title: A Phase 1/2 Study of GEN1286 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2024-11-12
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: No randomization will be performed in Part A (dose escalation- sequential assignment). In Part B (tumor-specific expansion- parallel assignment), participants in each cohort will be randomized with a 1:1 ratio to receive one of the expansion doses of GEN1286.
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to evaluate the safety, tolerability, pharmacokinetics (PK), anti-tumor activity and immunogenic potential of GEN1286 in participants with advanced solid tumors.

This trial consists of 2 parts:

* Part A: Dose escalation and dose level expansion
* Part B: Tumor-specific expansion with dose optimization


Eligibility criteria: Key Inclusion Criteria:

* Participants must be ≥ 18 years of age at the time of informed consent; have measurable disease according to RECIST 1.1; Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; adequate organ, bone marrow, liver, coagulation, and renal function; and be willing to provide a pretreatment tumor specimen.
* All participants must have pathologically confirmed diagnosis of advanced solid tumor.
* Participants must have metastatic or unresectable locally advanced, recurrent disease not amenable to further local therapy and must have previously received therapies known to confer clinical benefit (unless ineligible to receive, refused to receive, or therapy is unavailable in the region).

Key Exclusion Criteria:

* Prior treatment with topoisomerase 1-based antibody-drug conjugate (ADC) therapy.

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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose until 12 months post last dose of study drug or withdrawal of consent, death, or study closure, whichever occurs first (Up to approximately 3 years 9 months)
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: During first cycle (Cycle length=21 days)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years 9 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 3 years 9 months
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 3 years 9 months
measure: Duration of Objective Response (DOR)
timeFrame: Up to approximately 3 years 9 months
measure: Area Under the Plasma or Serum Concentration Time Curve (AUC) of GEN1286 Related Analytes- Antibody-Conjugated Exatecan, Total Antibody (Tab) and u-Exatecan
timeFrame: Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
measure: Maximum Observed Plasma or Serum Concentration (Cmax) of GEN1286 Related Analytes- Antibody-Conjugated Exatecan, Tab and u-Exatecan
timeFrame: Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
measure: Time to Reach Cmax (Tmax) of GEN1286 Related Analytes- Antibody-Conjugated Exatecan, Tab and u-Exatecan
timeFrame: Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
measure: Apparent Terminal Half-life (t1/2) of GEN1286 Related Analytes- Antibody-Conjugated Exatecan, Tab and u-Exatecan
timeFrame: Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
measure: Clearance (CL) of GEN1286 Related Analytes- Antibody-conjugated Exatecan, Tab and u-Exatecan
timeFrame: Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
measure: Volume of Distribution (Vz) of GEN1286 Related Analytes- Antibody-conjugated Exatecan, Tab and u-Exatecan
timeFrame: Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
measure: Trough Concentrations (Ctrough) of GEN1286 Related Analytes- Antibody-conjugated Exatecan, Tab and u-Exatecan
timeFrame: Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
measure: Number of Participants with Antidrug Antibodies (ADA) to GEN1286
timeFrame: Up to approximately 2 years 9 months
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: San Antonio
country: United States
facility: START San Antonio
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: