TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors
- Conditions
- Head and Neck Squamous Cell CarcinomaRenal Cell CancerCastrate Resistant Prostate CancerNon Small Cell Lung Cancer
- Interventions
- Drug: TT-10
- Registration Number
- NCT04969315
- Lead Sponsor
- Portage Biotech
- Brief Summary
The purpose of this study is to evaluate the safety and tolerability of orally administered TT-10 in subjects with advanced selected solid tumors. The dose escalation portion of the study will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of TT-10.
- Detailed Description
Multicenter, open-label dose-escalation Phase I/II clinical study, designed to evaluate the safety, tolerability, PK, PD, anti-tumor activity, and efficacy of TT-10 in subjects diagnosed with advanced Renal cell cancer (RCC), castrate resistant prostate cancer (CRPC) and Non-small cell lung cancer (NSCLC); who have failed or are not eligible for standard of care treatment.
The study will be conducted in two phases. Dose escalation (Phase 1) will be to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), safety and tolerability of TT-10 in subjects with advanced subjects diagnosed with advanced Renal cell cancer (RCC), castrate resistant prostate cancer (CRPC) and Non-small cell lung cancer (NSCLC); who have failed or are not eligible for standard of care treatment. Dose expansion (Phase 2) will be to further explore the safety and tolerability of the MTD and/or RP2D, PK, PD, anti-tumor activity, and efficacy of TT-10.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 90
Not provided
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Major surgery within 4 weeks prior to Screening
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Participants with active central nervous system (CNS) metastases; however, participants who have undergone radiation and/or surgery for the treatment of CNS metastases, who are neurologically stable, and who are no longer taking pharmacologic doses of corticosteroids are eligible; participants with leptomeningeal metastases are not eligible.
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Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
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Prior anti-cancer therapy within 4 weeks prior to the start of study intervention. A 2 week washout is acceptable for short-acting drugs (eg, tyrosine kinase inhibitors). Any treatment-related toxicities must be resolved to Grade 0 - 1.
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Human immunodeficiency virus-infected participants
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Participants who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment.
Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- As mandated by local health authority
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Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at Screening. Note: Participants must have completed curative antiviral therapy at least 4 weeks prior to enrollment.
Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- As mandated by local health authority
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Participants who require immunosuppressive therapy including, but not limited to, treatment with corticosteroids in pharmacologic doses (equivalent to ≥ 10 mg prednisone daily), cyclosporine, mycophenolate, azathioprine, methotrexate, adalimumab, infliximab, vedolizumab, tofacitinib, dupilumab, rituximab, etc. or systemic steroids (except for steroid use as cortisol replacement therapy in documented adrenal insufficiency)
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Participants requiring administration of drugs known to be strong inhibitors or inducers of CYP3A4, 2C9 or 2C19
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Participants requiring drugs that modify gastric pH, such as proton-pump inhibitors, H2 blockers or antacids (eg, calcium, magnesium or aluminum containing over-the-counter medications)
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Ongoing systemic bacterial, fungal or viral infections at Screening
- NOTE: Participants on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met
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Administration of a live vaccine within 6 weeks of first dose of study intervention. Messenger ribonucleic acid vaccines for the prevention of Coronavirus Disease 2019 (COVID-19) infection are permitted.
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Baseline QT interval corrected with Fridericia's method (QTcF) > 470 ms (average of triplicate readings)
- NOTE: Criterion does not apply to participants with a right or left bundle branch block.
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Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
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Female participants who are pregnant or breastfeeding
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Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix or prostate intraepithelial neoplasia
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Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
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History of peptic ulcer and/or gastrointestinal bleed within the past 6 months prior to Screening
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History of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening
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Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the participant associated with his or her participation in the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Multiple Ascending Dose TT-10 3+3 Dose escalation until MTD and/or R2PD of TT-10 is determined
- Primary Outcome Measures
Name Time Method Number of subjects with Dose Limiting Toxicities (DLTs) of TT-10 during the dose escalation phase 28 Days All toxicities will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Define the maximum tolerated dose (MTD) or phase 2 recommended dose of TT-10 during the dose escalation phase Through study completion, an average of 1 year To confirm the maximum tolerated dose (MTD) of TT-10, defined as the highest dose level at which \<2 out of 6 participants experience a dose-limiting toxicity
Expansion cohort primary objective - safety Through study completion, an average of 1 year Incidence and severity of treatment-related adverse events (TRAEs) in participants treated at the recommended phase 2 dose in the expansion phase
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years) ORR is to be reported as the proportion of patients who have a Complete Response or Partial Response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Duration of Response (DoR) From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years) Defined as the time from first documented objective response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 to the date of first documented radiographic progression of disease (PD) or death.
Progression Free Survival (PFS) From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years) Time from first dose to the date of the first confirmed documented progression per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Peak serum concentration (Cmax) of TT-10 Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose PK Parameter
Area under the serum concentration versus time curve (AUC) of TT-10 Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose PK Parameter
Half-life of TT-10 Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose PK Parameter
Trial Locations
- Locations (8)
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of California San Francisco UCSF
🇺🇸San Francisco, California, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Jefferson Health-Thomas Jefferson University Hospitals
🇺🇸Philadelphia, Pennsylvania, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Sarah Cannon Research Institute Denver
🇺🇸Denver, Colorado, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States