A Phase 1/2 Study of GEN1286 in Patients With Advanced Solid Tumors

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

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: GEN1286

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START MidWest
  • Texas
    • San Antonio, Texas, United States, 78229
      • START San Antonio
  • Utah
    • West Valley City, Utah, United States, 84119
      • START Mountain Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GEN1286	Drug: GEN1286; Specified dose on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities (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 (Cycle length=21 days)
Number of Participants With Adverse Events (AEs)		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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of participants achieving a partial response (PR) or complete response (CR) as assessed by the investigator based on response evaluation criteria in solid tumors (RECIST) version 1.1.	Up to approximately 3 years 9 months
Disease Control Rate (DCR)	DCR is defined as the percentage of participants with stable disease (SD) or achieving a PR or CR based on RECIST version 1.1 as assessed by the investigator.	Up to approximately 3 years 9 months
Progression Free Survival (PFS)	PFS is defined as the time from the start of any treatment to the date of the first documented progression or death due to any cause, whichever occurs first based on RECIST version 1.1 as assessed by the investigator.	Up to approximately 3 years 9 months
Duration of Objective Response (DOR)	DOR is defined as the time from the first documentation of an objective tumor response (CR or PR) to the first documentation of tumor progression or to death due to any cause, whichever comes first based on RECIST version 1.1 as assessed by the investigator.	Up to approximately 3 years 9 months
Area Under the Plasma or Serum Concentration Time Curve (AUC) of GEN1286 Related Analytes- Antibody-Conjugated Exatecan, Total Antibody (Tab) and u-Exatecan		Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
Maximum Observed Plasma or Serum Concentration (Cmax) of GEN1286 Related Analytes- Antibody-Conjugated Exatecan, Tab and u-Exatecan		Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
Apparent Terminal Half-life (t1/2) of GEN1286 Related Analytes- Antibody-Conjugated Exatecan, Tab and u-Exatecan		Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
Trough Concentrations (Ctrough) of GEN1286 Related Analytes- Antibody-conjugated Exatecan, Tab and u-Exatecan		Predose and postdose at multiple timepoints at end of each cycle, up to approximately 2 years 9 months (Cycle length=21 days)
Number of Participants with Antidrug Antibodies (ADA) to GEN1286		Up to approximately 2 years 9 months

Collaborators and Investigators

• Sponsor: Genmab
• Investigators: Study Director: Study Official, Genmab

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2024
• Primary Completion (Actual): March 30, 2026
• Study Completion (Actual): March 30, 2026

Study Registration Dates

• First Submitted: November 11, 2024
• First Submitted That Met QC Criteria: November 11, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GCT1286-01; PRO1286-001 (Other Identifier: Sponsor identifier); CTR20250215 (Registry Identifier: China Drug Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No