Endometrial Cancer, GastroEsophageal Cancer, Non-small Cell Lung Cancer, Ovarian Cancer, Triple Negative Breast Cancer, Urothelial Carcinoma
Conditions
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.
Interventions
DRUGGEN1107
IV infusion of GEN1107
Sponsors
Genmab
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Modified toxicity probability interval (mTPI)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events | Through end of treatment, up to approximately 1 year | Type, incidence, severity, seriousness, and relatedness of adverse events. |
| Number of Participants with Dose Limiting Toxicities (DLTs) | Day 1 up to a maximum of Day 28 | Incidence of dose limiting toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Through end of treatment, up to approximately 1 year | Participants who achieve partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. |
| Disease Control Rate | Through end of treatment, up to approximately 1 year | Participants who achieve stable disease, partial or complete response per RECIST v1.1 criteria. |
| Progression-free Survival | Up to approximately 18 months | Time from start of treatment to first documented disease progression or death. |
| Duration of Objective Response | 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 | Time from the first documentation of an objective tumor response (complete response or partial response) to the first documented tumor progression or death. |
| Pharmacokinetic Parameter Area Under the Curve (AUC) for GEN1107 | Varying timepoints through end of treatment, up to approximately 1 year | Measure of GEN1107 AUC in plasma. |
| Pharmacokinetic Parameter Maximum Concentration (Cmax) for GEN1107 | Varying timepoints through end of treatment, up to approximately 1 year | Measure of the Cmax of GEN1107 in plasma. |
| Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for GEN1107 | Varying timepoints through end of treatment, up to approximately 1 year | Measure of the Tmax of GEN1107 in plasma. |
| Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for GEN1107 | Varying timepoints through end of treatment, up to approximately 1 year | Measure of t1/2 of GEN1107 in plasma. |
| Pharmacokinetic Parameter Trough Concentration (Ctrough) for GEN1107 | Varying timepoints through end of treatment, up to approximately 1 year | Measure of the Ctrough of GEN1107 in plasma. |
| 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 | — |
Countries
China, United States
Contacts
STUDY_DIRECTORStudy Official
Genmab
Outcome results
None listed