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

NCT07814248 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TS-104-101
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 3

Brief Summary

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. The main goals of this study are to:

• Find the recommended dose of TS-104 that can safely be given to participants
• Learn more about the side effects of TS-104
• Learn more about the effectiveness of TS-104
• Learn more about the pharmacokinetics of TS-104

Conditions

NSCLC (Non-small Cell Lung Cancer); HNSCC; Endometrial; Ovarian Cancer; Esophageal Cancer; Head & Neck Cancer; Gastric Cancer (GC); Endometrial Cancer

Keywords

TS-104; TwoStep; NSCLC; HNSCC; Gastric Cancer; Endometrial Cancer; Esophageal Cancer; Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Adverse Events Following Administration of TS-104

  To assess safety and tolerability. Safety reported as incidence of adverse events using CTCAE v6.0 criteria.

  From the first dose of TS-104 until 28 days after the last dose of TS-104 (up to 26 months)

• Number of Participants with Dose Limiting Toxicities (DLTs) from TS-104

  Number of participants who experience TS-104 dose limiting toxicities.

  Up to 21 days (for 2Q3W regimen) or Up to 28 days (for Q2W regimen) from the first dose

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Every six weeks from the first dose of TS-104 for the first 8 cycles, and then every 8 weeks beginning with Cycle 10 until disease progression or death. (up to 26 months)

• Duration of Response (DOR)

  Every six weeks from the first dose for the first 8 cycles, and then every 8 weeks beginning with Cycle 10 until disease progression or death.

• Progression-Free Survival (PFS)

  Every six weeks from the first dose for the first 8 cycles, and then every 8 weeks beginning with Cycle 10 until disease progression or death.

• Overall Survival (OS)

  From first dose until death or study completion, assessed up to approximately 12 months

Study Arms (3)

Dose Escalation- 2Q3W

EXPERIMENTAL

TS-104 will be administered 2Q3W (i.e. on days 1 and 8 every 21 days)

Drug: TS-104

Dose Escalation- Q2W

EXPERIMENTAL

TS-104 will be administered Q2W (i.e. on days 1 and 15 every 28 days)

Drug: TS-104

Dose Expansion

EXPERIMENTAL

TS-104 will be administered either 2Q3W (i.e. on days 1 and 8 every 21 days) or Q2W (i.e. on days 1 and 15 every 28 days)

Drug: TS-104

Interventions

TS-104 DRUG

TS-104 is a peptide-drug conjugate that delivers the anticancer drug MMAE to tumors using a targeting peptide that binds to certain integrins commonly found on solid tumors.

Dose Escalation- 2Q3W; Dose Escalation- Q2W; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males \& females ≥18 years of age at the time of consent
• Willingness to provide written informed consent, according to local guidelines.
• Subjects who have histologically or cytologically documented, unresectable locally advanced, or metastatic solid malignancy that is progressing or has failed the minimum therapies listed below or who are intolerant of, ineligible for, or refuse standard of care (SOC) therapy according to local guidelines:
• Non-small cell lung cancer (NSCLC)
• Head and neck squamous cell carcinoma (HNSCC)
• Esophageal cancer
• Endometrial cancer
• Ovarian cancer
• Gastric cancer
• Subjects must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• All subjects must have tumor tissue available for retrospective analysis
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate organ function as defined by the following criteria:
• AST and ALT ≤2.5×ULN or ≤5×ULN for subjects with liver metastases
• Total serum bilirubin ≤1.5×ULN except in the presence of Gilbert's Syndrome where direct bilirubin should be ≤ULN

You may not qualify if:

• 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

Sponsors & Collaborators

• TwoStep Therapeutics, Inc.: lead

Study Sites (3)

Site 06

Maumee, Ohio, 43537, United States

RECRUITING

Site 02

Portland, Oregon, 97239, United States

RECRUITING

Site 04

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Ovarian Neoplasms; Esophageal Neoplasms; Head and Neck Neoplasms; Stomach Neoplasms; Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Neoplasms; Uterine Diseases

Central Study Contacts

TwoStep Clinical Trials

CONTACT

ClinicalTrials@twosteptx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 10, 2026
• Study Start: September 2, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 30, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)