A Phase 1, First-in-Human (FIH), Open-Label, Dose-Escalation and Dose Expansion Study of the Peptide Drug Conjugate (PDC), TS-104, as a Monotherapy in Subjects With Select Advanced Solid Tumors

Unresolved toxicity higher than Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v 6.0 (or higher) attributed to any prior therapy/procedure at Screening, except for alopecia, well-controlled Grade 2 hypothyroidism, or Grade 2 adrenal insufficiency that is actively managed with appropriate therapy

Subjects with ongoing sensory or motor neuropathy ≥Grade 2

Subjects with active or chronic keratitis or corneal disorders, including ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the Investigator.

Known sensitivity to any of the ingredients of TS-104 or MMAE

Prior treatment with tubulin-inhibitor-based drug conjugates, including antibody-drug conjugates (ADCs) with tubulin inhibitor payloads, ie, Emrelis (MMAE payload) for c-Met-high NSCLC or Elahere (DM4 payload) for FRα-high ovarian cancer. For clarity, prior treatment with standard taxane-based chemotherapy (eg, paclitaxel) is permitted.

Subjects currently receiving cancer therapy (ie, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery, and/or tumor embolization) or expected to require any other form of antineoplastic therapy while on study.

Subject with history of other malignancy other than the one for which they participate in the study (exceptions include definitively resected basal cell carcinoma and other in situ cancers) - unless the subject has undergone curative therapy with no evidence of that disease for 3 years

Major surgery or planned major surgery (excluding placement of vascular access device) within 4 weeks of Cycle 1 Day 1 (C1D1)

Subjects who are currently pregnant or breastfeeding

Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, uncontrolled diabetes mellitus, active or chronic bleeding event within 28 days prior to C1D1, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician. This includes any preexisting medical history that could impair the proper assessment of the study results (eg, severe pulmonary function compromise unrelated to underlying malignancy).

≥Grade 3 pulmonary disease unrelated to underlying malignancy

History of noninfectious interstitial lung disease (ILD) or pneumonitis that required steroids, current ILD or pneumonitis, or suspected ILD or pneumonitis that cannot be ruled out by imaging at Screening or the presence of residual symptoms

Clinically significant, uncontrolled cardiovascular disease including: myocardial infarction or unstable angina within the last 6 months, symptomatic congestive heart failure (New York Heart Association Classification \>Class II), or serious uncontrolled cardiac arrhythmia within the last 6 months of Screening

History of long QT syndrome or subject whose corrected QT interval measured by Fridericia's method at Screening is prolonged (\>470 msec)

Uncontrolled hypertension, defined as systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg despite optimal medical management

Current treatment with strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4 or inhibitors of P-glycoprotein (P-gp) including herbal or food based

Known active central nervous system metastases.

What this study is about