Endometrial, Endometrial Cancer, Esophageal Cancer, Gastric Cancer (GC), Head & Neck Cancer, HNSCC, NSCLC (Non-small Cell Lung Cancer), Ovarian Cancer
Conditions
Keywords
TS-104, TwoStep, NSCLC, HNSCC, Gastric Cancer, Endometrial Cancer, Esophageal Cancer, Ovarian Cancer
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
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: 1. 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. 2. 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).
Interventions
DRUGTS-104
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.
Sponsors
TwoStep Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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: 1. Non-small cell lung cancer (NSCLC) 2. Head and neck squamous cell carcinoma (HNSCC) 3. Esophageal cancer 4. Endometrial cancer 5. Ovarian cancer 6. 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: 1. AST and ALT ≤2.5×ULN or ≤5×ULN for subjects with liver metastases 2. Total serum bilirubin ≤1.5×ULN except in the presence of Gilbert's Syndrome where direct bilirubin should be ≤ULN 3. ANC ≥1.5×109/L 4. Platelets ≥100×109/L without transfusion support within 14 days prior to study treatment 5. Hemoglobin ≥9.0 g/dL without transfusion support within 14 days prior to study treatment 6. Calculated creatinine clearance ≥60 mL/min by Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 7. 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events Following Administration of TS-104 | From the first dose of TS-104 until 28 days after the last dose of TS-104 (up to 26 months) | To assess safety and tolerability. Safety reported as incidence of adverse events using CTCAE v6.0 criteria. |
| Number of Participants with Dose Limiting Toxicities (DLTs) from TS-104 | Up to 21 days (for 2Q3W regimen) or Up to 28 days (for Q2W regimen) from the first dose | Number of participants who experience TS-104 dose limiting toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Percentage of participants achieving a best overall response of complete response (CR) or partial response (PR), as assessed by RECIST v1.1 |
| 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. | Time from first documented CR or PR to first documented disease progression or death from any cause, among subjects who achieve an objective response |
| 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. | Time from first dose of study drug to first documented disease progression or death from any cause, whichever occurs first |
| Overall Survival (OS) | From first dose until death or study completion, assessed up to approximately 12 months | Time from first dose of study drug to death from any cause |
Outcome results
None listed