A Study of SGN-STNV in Advanced Solid Tumors

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.

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.

Eligibility Criteria:
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.