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
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
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.
To eligible for inclusion in the dose escalation cohort or expansion cohort 1 in this
study, subjects must meet all of the following criteria:
1. Subjects must be ≥18 years of age.
2. Subjects or their legal representative must be able to provide written informed
consent to participate in the trial prior to the performance of any study-specific
3. Diagnosis of histologically or cytologically confirmed advanced selected solid tumors
- Cohort A dose escalation: 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.
- Cohort B: Advanced RCC who have failed or are not eligible for standard of care
- Cohort C: Advanced CRPC who have failed or are not eligible for standard of care
- Cohort D: Advanced NSCLC who have failed or are not eligible for standard of care
- Cohort E: Exploratory Biopsy: Inclusive of subjects w/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.
4. ECOG performance status (PS) score 0-1
5. Have measurable disease per RECIST 1.1 or (for subjects in the expansion cohorts)
irRECIST 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.
6. Subjects must have locally advanced, recurrent or metastatic neoplastic disease that
is not curable by currently available local therapies.
7. Failure to respond to standard therapy, or for whom no appropriate therapies are
available (based on the judgment of the Investigator)
8. Cohort E Only: Fresh tissue sample obtained prior to treatment initiation and agree to
on treatment biopsy from same lesion.
9. Life expectancy of ≥ 3 months
10. Subjects 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
11. Subjects must have adequate hepatic function based on the following:
- Total bilirubin <1.5 × upper limit of normal (ULN) (unless elevated due to
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 ×
ULN for subjects with known hepatic metastases)
12. Subjects must have adequate renal function based on the following:
- Serum creatinine ≤1.5 × ULN; or
- Serum creatinine clearance ≥ 45 mL/min (≥ 30 mL/min for subjects), as determined
by Cockcroft-Gault equation
13. Human immunodeficiency virus (HIV) infected subjects must be on antiretroviral therapy
(ART) and have a well-controlled HIV infection/disease defined as:
1. Subjects on ART must have a CD4+ T cell count >350 cells/mm3 at time of screening
2. Subjects on ART must have achieved and maintained virologic suppression defined
as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification
(below the limit of detection) using the locally available assay at the time of
screening and for at least 12 weeks prior to screening
3. Subjects on ART must have been on a stable regimen, without changes in drugs or
dose modification, for at least 4 weeks prior to study entry (Day 1).
14. For women of childbearing potential (WCBP): negative urine pregnancy test (UPT) within
1 week before first treatment (WCBP defined as a sexually mature woman who has not
undergone surgical sterilization or who has not been naturally post-menopausal for at
least 12 consecutive months for women > 55 years of age). WCBP should be placed on
effective birth control directly after testing negative for pregnancy; if not, then
WCBP should have a UPT on Day 1 of every cycle, prior to drug administration. Any
positive or indeterminant UPT result must be confirmed by Serum.
15. Female subjects of childbearing potential must use a highly effective mode of
contraception or abstain from heterosexual activity for the duration of the trial and
for 120 days following the last dose of study medication. A female is NOT of
childbearing potential if she has undergone bilateral salpingoophorectomy or is
menopausal, defined as an absence of menses for 12 consecutive months. Male subjects
must agree to use highly effective contraception.
16. Ability to adhere to the study visit schedule and all protocol requirements
Subjects will be excluded from the study if they satisfy any of the following criteria at
the screening visit unless otherwise stated:
Subjects are to be excluded from the study if they meet any of the following criteria:
1. Major surgery within 4 weeks prior to Screening
2. Subjects with active central nervous system (CNS) metastases; however, subjects 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; subjects with leptomeningeal metastases are not
3. Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects
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.
4. Primary CNS malignancy
5. HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman
6. Subjects 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: Subjects should remain on antiviral therapy throughout study intervention and
follow local guidelines for HBV antiviral therapy post completion of study
Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- As mandated by local health authority.
7. Subjects with a history of hepatitis C virus (HCV) infection are eligible if HCV viral
load is undetectable at screening. Note: Subjects 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.
8. Subjects 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
9. Ongoing systemic bacterial, fungal, or viral infections at Screening
a. NOTE: Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not
specifically excluded if all other inclusion/exclusion criteria are met
10. Administration of a live vaccine within 6 weeks of first dose of study drug
11. Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of
a. NOTE: Criterion does not apply to subjects with a right or left bundle branch
12. Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg,
gastric bypass surgery, gastrectomy)
13. Female subjects who are pregnant or breastfeeding
14. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of
the cervix, or prostate intraepithelial neoplasia
15. 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
16. History of peptic ulcer and/or gastrointestinal bleed within the past 6 months prior
17. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia
requiring medication or mechanical control within the last 6 months prior to Screening
18. 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 subject
associated with his or her participation in the study.