NSCLC (Non-small Cell Lung Cancer)Phase 1NCT07814248
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
A Phase 1 study testing TS-104 in people with NSCLC (Non-small Cell Lung Cancer) and HNSCC, run by TwoStep Therapeutics, Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC (Non-small Cell Lung Cancer), HNSCC, Endometrial
- What is being tested?
- TS-104
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 3 sitesUnited States
- Study dates
- 2 Sep 2026to Dec 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 22Show fewer
- 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
- ANC ≥1.5×109/L
- Platelets ≥100×109/L without transfusion support within 14 days prior to study treatment
- Hemoglobin ≥9.0 g/dL without transfusion support within 14 days prior to study treatment
- Calculated creatinine clearance ≥60 mL/min by Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Coagulation tests ≤1.5×ULN unless subject is receiving anticoagulant therapy, as long as prothrombin time (PT), International Normalized Ratio (INR), or activated partial thromboplastin time (aPTT) is within the therapeutic range of intended use of anticoagulants
- Negative serum pregnancy test for women of childbearing potential (WOCBP) at Screening and willingness to use highly effective contraception for the duration of the trial and for 6 months following the last dose of TS-104
- Male subjects must agree to use a highly effective method of contraception while on study and for 6 months following the last dose of TS-104
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
TwoStep Clinical Trials contact
United States3 sites, 3 recruiting
- Recruiting
Site 04
Fairfax, Virginia, 22031
- Recruiting
Site 06
Maumee, Ohio, 43537
- Recruiting
Site 02
Portland, Oregon, 97239
About this study
Official title: 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 Advanced Solid Tumors
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
Read the detailed description
This study is testing an investigational drug called TS-104 in participants with select advanced solid tumors that have not responded to other treatments. The main purpose is to find out whether TS-104 is safe and how well it is tolerated. It will also study whether TS-104 works to treat solid tumors.
TS-104 is a peptide-drug conjugate that delivers the anticancer drug monomethyl auristatin E (MMAE) to tumors using a targeting peptide that binds to certain integrins commonly found on solid tumors
The study has two parts:
- Dose Escalation: when doses of TS-104 are gradually increased are tested to find an appropriate dose. Dose escalation will enroll participants with advanced solid tumors in Head \& Neck Squamous Cell Carcinoma (HNSCC), Non-Smal Cell Lung Cancer (NSCLC), Esophageal, Gastric, Ovarian, and Endometrial.
- Dose Expansion: when a specific dose or doses will be tested in more participants.
TS-104 will be given on one of two schedules: twice every three weeks (a 21-day treatment cycle) or once every two weeks (a 28-day treatment cycle).
- Conditions
- NSCLC (Non-small Cell Lung Cancer), HNSCC, Endometrial, Ovarian Cancer, Esophageal Cancer, Head & Neck Cancer
- Being tested
- TS-104
- Keywords
- TS-104, TwoStep, NSCLC, HNSCC, Gastric Cancer, Endometrial Cancer, Esophageal Cancer, Ovarian Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Ovarian Neoplasms, Esophageal Neoplasms, Head and Neck Neoplasms, Stomach Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TS-104Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation- 2Q3W | Experimental | TS-104 will be administered 2Q3W (i.e. on days 1 and 8 every 21 days) Receives: Drug: TS-104 |
| Dose Escalation- Q2W | Experimental | TS-104 will be administered Q2W (i.e. on days 1 and 15 every 28 days) Receives: 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) Receives: Drug: TS-104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Percentage of participants achieving a best overall response of complete response (CR) or partial response (PR), as assessed by RECIST v1.1
Measured: 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)
Time from first documented CR or PR to first documented disease progression or death from any cause, among subjects who achieve an objective response
Measured: 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)
Time from first dose of study drug to first documented disease progression or death from any cause, whichever occurs first
Measured: 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)
Time from first dose of study drug to death from any cause
Measured: From first dose until death or study completion, assessed up to approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2026
- Study start2 Sep 2026
- Primary completionAug 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC (Non-small Cell Lung Cancer)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TwoStep Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07814248
- Sponsor's protocol ID
- TS-104-101
- Status last verified
- Sep 2026
- First submitted
- 31 Aug 2026
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No