Phase I/II First-in-Human Study of TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors
Description
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.
Phase
N/AInclusion and Exclusion Criteria
- Inclusion Criteria
- Participants must be ≥ 18 years of age.
- Participants or their legal representative must be able to provide written informed consent to participate in the study prior to the performance of any study-specific procedures.
- Diagnosis of histologically or cytologically confirmed advanced selected solid tumors - Cohort A dose escalation: RCC, CRPC and NSCLC who have failed or are not eligible for standard of care treatment. - Cohort B: Metastatic RCC who have failed or are not eligible for standard of care treatment. - Cohort C: Metastatic CRPC who have failed or are not eligible for standard of care treatment. - Cohort D: Metastatic NSCLC who have failed or are not eligible for standard of care treatment. - Cohort E: Exploratory Biopsy - Inclusive of participants with RCC, CRPC and/or NSCLC who have failed or are not eligible for standard of care treatment and have an accessible tumor for pre- and post dose biopsies.
- Eastern Cooperative Oncology Group performance status score 0 - 1
- Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Failure to respond to standard therapy, or for whom no appropriate therapies are available (based on the judgment of the investigator)
- Cohort E Only: Fresh tissue sample obtained prior to treatment initiation and agree to on-treatment biopsy from same lesion.
- Life expectancy of ≥ 3 months
- Participants must have adequate hematologic function based on the following: - Absolute neutrophil count ≥ 1.5 x 109/L - Platelet count ≥ 100 x 109/L - Hemoglobin ≥ 9.0 g/dL
- Participants must have adequate hepatic function based on the following: - Total bilirubin < 1.5 x upper limit of normal (ULN) (unless elevated due to Gilbert's syndrome) - Alanine aminotransferase/aspartate aminotransferase ≤ 2.5 x ULN (≤ 5 x ULN for participants with known hepatic metastases)
- Participants must have adequate renal function based on the following: - Serum creatinine ≤ 1.5 x ULN; or - Serum creatinine clearance ≥ 60 mL/min, as determined by Cockcroft-Gault equation Exclusion Criteria:
- Major surgery within 4 weeks prior to Screening
- 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.
- 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.
- 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.
- Human immunodeficiency virus-infected participants
- 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
- 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
- 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)
- Participants requiring administration of drugs known to be strong inhibitors or inducers of CYP3A4, 2C9 or 2C19
- 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)
- 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
- 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.
- 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.
- Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
- Female participants who are pregnant or breastfeeding
- Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix or prostate intraepithelial neoplasia
- 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
- History of peptic ulcer and/or gastrointestinal bleed within the past 6 months prior to Screening
- History of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening
- 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
Sites
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.
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