A Study of SGN-STNV in Advanced Solid Tumors

Study Overview
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Brief Summary
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This trial will look at a drug called SGN-STNV to find out whether it is safe for patients with solid tumors. It will study SGN-STNV to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study how well SGN-STNV works to treat solid tumors. The study will have two parts. Part A of the study will find out how much SGN-STNV should be given to patients. Part B will use the dose found in Part A to find out how safe SGN-STNV is and if it works to treat certain types of solid tumors.

Detailed Description
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The study will include dose escalation (Part A) and dose expansion (Part B), with multiple disease-specific cohorts and a biology cohort in dose expansion. The biology cohort will require additional biopsies. At the completion of dose escalation, up to 5 disease specific expansion cohorts and 1 biology expansion cohort may be activated by the sponsor in consultation with the Safety Monitoring Committee (SMC). Expansion cohorts in Part B will enroll subjects with selected tumors that are eligible for enrollment in Part A. The dose(s) to be examined in Part B will be at or below the maximum tolerated dose and/or the recommended dose determined in Part A. The recommended dose and/or schedule may differ between cohorts.

Official Title
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A Phase 1 Study of SGN-STNV in Advanced Solid Tumors

Conditions
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Esophageal Neoplasms, Carcinoma, Non-Small Cell Lung, HER2 Negative Breast Neoplasms, Ovarian Neoplasms, Uterine Cervical Neoplasms, Endometrial Neoplasms, Gastroesophageal Junction Carcinoma, Stomach Neoplasms, Colorectal Neoplasms, Exocrine Pancreatic Adenocarcinoma, Appendiceal Adenocarcinoma, Pseudomyxoma Peritonei

Intervention / Treatment
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* Drug: SGN-STNV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease indication Must have disease that is relapsed or refractory or be intolerant to standard-of-care therapies and should have no appropriate standard-of-care therapeutic option. Non-small cell lung cancer (NSCLC) HER2 negative breast cancer Ovarian cancer Cervical cancer Endometrial cancer Esophageal cancer Gastric cancer and GEJ carcinoma Colorectal cancer Exocrine pancreatic adenocarcinoma Appendiceal adenocarcinoma and pseudomyxoma peritonei of unknown origin Participants enrolled in the following study parts should have an appropriate tumor site that satisfies the following criteria: Site has tumor that is not a target lesion and has not been previously irradiated (unless progression has occurred since end of radiotherapy) Site has tumor that is accessible for a minimally invasive biopsy that does not present a significant risk, AND Participant must agree to a biopsy as follows Disease-specific expansion cohorts: pre-treatment biopsy, unless medically infeasible following consultation with the medical monitor Biology expansion cohort: pretreatment biopsy (required) and additional on-treatment biopsy during Cycle 1 (unless medically infeasible following consultation with the medical monitor) Measurable disease per the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) at baseline An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Adequate renal, hepatic, and hematologic function Exclusion Criteria 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. Known active central nervous system metastases Carcinomatous meningitis Previous receipt of monomethylauristatin E (MMAE)-containing drugs Pre-existing neuropathy ≥ Grade 2 per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 Any uncontrolled ≥ Grade 3 (per the NCI CTCAE, Version 5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of SGN-STNV There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGN-STNV<br>SGN-STNV monotherapy | Drug: SGN-STNV<br>* Given into the vein (IV; intravenously)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | To be summarized using descriptive statistics | Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years | 
| Incidence of laboratory abnormalities | To be summarized using descriptive statistics | Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years | 
| Incidence of dose limiting toxicities | To be summarized using descriptive statistics | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) as assessed by the investigator per RECIST v1.1 | ORR is defined as the proportion of subjects achieving a partial response (PR) or complete response (CR). | Up to approximately 3 years | 
| Progression-free survival (PFS) | PFS is defined as the time from the start of any study treatment to first documentation of disease progression or to death due to any cause, whichever comes first. | Up to approximately 3 years | 
| Overall survival (OS) | OS is defined as the time from the start of any study treatment to the date of death due to any cause. | Up to approximately 3 years | 
| Duration of objective response (DOR) | DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression or to death due to any cause, whichever comes first. | Up to approximately 3 years | 
| Area under the concentration-time curve (AUC) | Pharmacokinetic (PK) endpoint | Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years | 
| Time to maximum concentration (Tmax) | PK endpoint | Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years | 
| Maximum concentration (Cmax) | PK endpoint | Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years | 
| Trough concentration (Ctrough) | PK endpoint | Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years | 
| Incidence of antidrug antibodies (ADA) | Immunogenicity endpoint | Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Non-Small Cell Lung Cancer, HER2-Negative Breast Cancer, High-Grade Serous Ovarian Cancer, HGSOC, Ovarian Cancer, Cervical Cancer, Endometrial Cancer, Esophageal Cancer, Gastric Cancer, GEJ Carcinoma, Colorectal Cancer, Seattle Genetics