PRO1107 in Patients With Advanced Solid Tumors

A Phase 1/2 Study of PRO1107 in Patients With Advanced Solid Tumors

This is a global, open-label, multicenter Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of GEN1107 (PRO1107) in participants with advanced solid tumors. This study consists of 2 parts, Part A: dose escalation and dose level expansion, and Part B: tumor specific expansion.

Study Overview

• Status: Terminated
• Conditions: Ovarian Cancer; Triple Negative Breast Cancer; Endometrial Cancer; Non-small Cell Lung Cancer; Urothelial Carcinoma; GastroEsophageal Cancer
• Intervention / Treatment: Drug: GEN1107

Detailed Description

This is a Phase 1/2 study of GEN1107, a protein tyrosine K 7 (PTK7) targeted antibody-drug conjugate (ADC), to evaluate the safety, tolerability, PK, and antitumor activity of GEN1107 in participants with advanced solid tumors, including ovarian cancer, endometrial cancer, triple negative breast cancer, non-small cell lung cancer, gastroesophageal cancer, and urothelial cancer. This study consists of 2 parts, Part A: Dose Escalation and Dose Level Expansion and Part B: Tumor Specific Expansion.

In Part A, GEN1107 will be administered in different dosing regimens via intravenous (IV) infusion.

Part B will be initiated at a dose level based on a comprehensive analysis of safety, tolerability, clinical PK, pharmacodynamics (PD) and activity data from Part A in up to 4 different tumor-specific cohorts of up to 40 participants per cohort.

Participants will continue to receive study treatment until the first instance of disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the Sponsor, pregnancy, or death.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Institution of Hunan Cancer Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • Florida
    • Sarasota, Florida, United States, 34236
      • Florida Cancer Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 78229
      • START Mountain Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

Part A:

• Pathologically confirmed diagnosis of one of the following tumor types:
• Ovarian cancer (epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer)
• Endometrial cancer (any subtype excluding sarcoma)
• Triple negative breast cancer (TNBC)

• Non-small cell lung cancer (NSCLC)

  • Metastatic or unresectable locally advanced, recurrent, disease not amenable to further local therapy following prior systemic therapies known to confer clinical benefit.

Part B:

• Participants must have a histologically or cytologically confirmed metastatic or unresectable solid malignancy as specified below:

  • Ovarian cancer
  • TNBC
  • Endometrial cancer
  • NSCLC
• Measurable disease at baseline as defined per RECIST, Version 1.1

Exclusion Criteria

• Prior treatment with anti-PTK7-directed therapy.
• Had progressive disease as best response while on treatment with an auristatin (eg, a vedotin or pelidotin)- based ADC as the most recent line of therapy.
• History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] ≥90%)
• Known active central nervous system metastases, including carcinomatous meningitis. Participants with brain metastases may participate provided the metastases have been treated and are stable for at least 4 weeks prior to the first dose of study drug, they have no new or enlarging brain metastases and have discontinued corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study drug. Participants with a history of brain metastases, suspected new brain metastases, or a diagnosis of NSCLC or breast cancer should have a computed tomography (CT)/ magnetic resonance imaging (MRI) scan of the brain at screening.
• Participants with active or chronic corneal disorders, history of corneal transplantation, or any clinically significant corneal disease that prevents adequate monitoring of potential drug-induced keratopathy. Note: Participants with other active ocular conditions requiring ongoing therapy and/or monitoring must be discussed with the sponsor prior to enrollment.

Additional protocol defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GEN1107; GEN1107 monotherapy in escalating doses in Part A and at the dose level in Part B.	Drug: GEN1107; IV infusion of GEN1107

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	Type, incidence, severity, seriousness, and relatedness of adverse events.	Through end of treatment, up to approximately 1 year
Number of Participants with Dose Limiting Toxicities (DLTs)	Incidence of dose limiting toxicities.	Day 1 up to a maximum of Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Participants who achieve partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.	Through end of treatment, up to approximately 1 year
Disease Control Rate	Participants who achieve stable disease, partial or complete response per RECIST v1.1 criteria.	Through end of treatment, up to approximately 1 year
Progression-free Survival	Time from start of treatment to first documented disease progression or death.	Up to approximately 18 months
Duration of Objective Response	Time from the first documentation of an objective tumor response (complete response or partial response) to the first documented tumor progression or death.	From date of enrollment until the date of first documented disease progression or date of study withdrawal, whichever came first, assessed up to 12 months
Pharmacokinetic Parameter Area Under the Curve (AUC) for GEN1107	Measure of GEN1107 AUC in plasma.	Varying timepoints through end of treatment, up to approximately 1 year
Pharmacokinetic Parameter Maximum Concentration (Cmax) for GEN1107	Measure of the Cmax of GEN1107 in plasma.	Varying timepoints through end of treatment, up to approximately 1 year
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for GEN1107	Measure of the Tmax of GEN1107 in plasma.	Varying timepoints through end of treatment, up to approximately 1 year
Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for GEN1107	Measure of t1/2 of GEN1107 in plasma.	Varying timepoints through end of treatment, up to approximately 1 year
Pharmacokinetic Parameter Trough Concentration (Ctrough) for GEN1107	Measure of the Ctrough of GEN1107 in plasma.	Varying timepoints through end of treatment, up to approximately 1 year
Cancer Antigen 125 (CA-125) Response per Gynecological Cancer Intergroup (GCIG) Criteria for Ovarian Cancer		Varying timepoints through end of treatment, up to approximately 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenic potential of PRO1107	Measure of anti-drug antibodies of PRO1107 in serum	Varying timepoints through end of treatment, up to approximately 1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Actual): August 18, 2025
• Study Completion (Actual): August 18, 2025

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Breast Neoplasms; Skin and Connective Tissue Diseases; Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Endometrial Neoplasms; Carcinoma, Transitional Cell
• Other Study ID Numbers: GCT1107-01; CTR20242075 (Registry Identifier: ChinaDrugTrials.org.cn); PRO1107-01 (Other Identifier: Secondary Protocol ID)

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
• product manufactured in and exported from the U.S.: No