Clinical trial NCT06171789: PRO1107 in Patients With Advanced Solid Tumors
Official title: A Phase 1/2 Study of PRO1107 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Endometrial Cancer
Ovarian Cancer
Triple Negative Breast Cancer
GastroEsophageal Cancer
Non-small Cell Lung Cancer
Urothelial Carcinoma
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2023-12-15
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Modified toxicity probability interval (mTPI)
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Through end of treatment, up to approximately 1 year
measure: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 up to a maximum of Day 28
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Through end of treatment, up to approximately 1 year
measure: Disease Control Rate
timeFrame: Through end of treatment, up to approximately 1 year
measure: Progression-free Survival
timeFrame: Up to approximately 18 months
measure: Duration of Objective Response
timeFrame: 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
measure: Pharmacokinetic Parameter Area Under the Curve (AUC) for GEN1107
timeFrame: Varying timepoints through end of treatment, up to approximately 1 year
measure: Pharmacokinetic Parameter Maximum Concentration (Cmax) for GEN1107
timeFrame: Varying timepoints through end of treatment, up to approximately 1 year
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for GEN1107
timeFrame: Varying timepoints through end of treatment, up to approximately 1 year
measure: Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for GEN1107
timeFrame: Varying timepoints through end of treatment, up to approximately 1 year
measure: Pharmacokinetic Parameter Trough Concentration (Ctrough) for GEN1107
timeFrame: Varying timepoints through end of treatment, up to approximately 1 year
measure: Number of Participants with Anti-drug Antibodies (ADAs)
timeFrame: Varying timepoints through end of treatment, up to approximately 1 year
measure: Cancer Antigen 125 (CA-125) Response per Gynecological Cancer Intergroup (GCIG) Criteria for Ovarian Cancer
timeFrame: Varying timepoints through end of treatment, up to approximately 1 year
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: START Mountain Cancer Center
state: Utah
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: