Prostate Cancer (CRPC)Phase 2NCT07871110
Safety, Efficacy and Pharmacokinetics of TT00420 Tablets Combined With Novel Endocrine Therapy in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC)
A Phase 2 study testing tinengotinib 10 mg QD plus darolutamide, tinengotinib 10 mg QD (2-week on / 1-week off) plus darolutamide and tinengotinib 10 mg QD plus enzalutamide in people with Prostate Cancer (CRPC), run by TransThera Sciences (Nanjing), Inc. at 16 sites in China.
Trial summary
The goal of this clinical trial is to learn if tinengotinib combined with darolutamide or enzalutamide works to treat participants with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior androgen receptor pathway inhibitors (ARPIs). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer (CRPC)
- What is being tested?
- tinengotinib 10 mg QD plus darolutamide, tinengotinib 10 mg QD (2-week on / 1-week off) plus darolutamide and tinengotinib 10 mg QD plus enzalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 16 sitesChina
- Study dates
- 18 Sep 2026to 30 Jun 2029
- Phase
- Phase 2
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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male aged >= 18 years at the time of signing the informed consent form (ICF).
- Histologically or cytologically confirmed prostate adenocarcinoma; neuroendocrine differentiation after prior treatment is permitted (patients with de novo neuroendocrine prostate cancer at initial diagnosis are excluded).
- Baseline imaging confirming metastatic lesions in bone (>=2 bone lesions) or soft tissue; lesions identified only by PET imaging are not acceptable.
- Receipt of continuous medical castration for >=90 days or prior surgical castration, with serum testosterone < 50 ng/dL (1.73 nmol/L) within 28 days prior to the first dose. Participants receiving medical castration with a luteinizing hormone-releasing hormone (LHRH) analogue must continue treatment throughout the study.
- Documented disease progression (per RECIST v1.1 and/or PCWG3) after >1 month of prior novel endocrine therapy (including abiraterone and AR inhibitors).
- Cohort B: Prior exposure to only one type of novel endocrine therapy.
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- Disease failure after <=1 line of chemotherapy administered during the castration-resistant phase (chemotherapy duration <=1 month and ADC agents are not counted as systemic chemotherapy).
- ECOG performance status <= 1.
- Adequate organ and bone marrow function (no hematopoietic growth factors, blood transfusion or related blood products within 14 days before the first dose).
- Must agree not to donate sperm or cryopreserve sperm for future assisted reproduction during study treatment and for 3 months after the last dose of study treatment. If the participant is spermatogenic and his female partner is of childbearing potential, highly effective contraception must be used.
- Able to provide informed consent and comply with study procedures.
Who cannot join
- Prior treatment with tyrosine kinase inhibitors (TKIs).
- Prior treatment with darolutamide or enzalutamide (except for treatment duration <= 1 month).
- Uncontrolled hypertension (systolic blood pressure >=150 mmHg or diastolic blood pressure >=100 mmHg; repeat measurement is permitted after an interval of >=10 minutes if abnormal), or a medical history of hypertensive crisis/hypertensive encephalopathy. Uncontrolled is defined as failure to achieve blood pressure control despite antihypertensive therapy with stable type/dose for at least 1 week.
- Concurrent central nervous system (CNS) metastases with radiological or symptomatic progression within 28 days prior to study treatment initiation.
- Concurrent other malignancies requiring active treatment. Malignancies not requiring treatment within 5 years and cured localized tumors such as basal cell carcinoma of the skin, papillary thyroid carcinoma, etc., are excluded from this criterion.
- Prior administration of other anti-tumor therapies within <=5 half-lives or 14 days (whichever is shorter) before initiation of study treatment, or failure to recover from adverse events of prior therapy (except for adverse events <= Grade 1 or <= Grade 2 adverse events judged by the investigator not to pose a safety risk). Sex hormone therapies other than LHRH agents must be discontinued >=7 days before study drug administration.
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- Receipt of extensive radiotherapy within 4 weeks prior to study treatment initiation, or palliative local radiotherapy within 2 weeks, or failure to recover from adverse events of prior therapy. (If the investigator considers that early initiation of study drug is in the participant's best interest based on benefit-risk assessment, study drug treatment may be started during the washout period upon sponsor approval.)
- Major surgery within 4 weeks prior to study treatment initiation, or failure to recover from surgical adverse events (except for adverse events <= Grade 1 or <= Grade 2 adverse events judged by the investigator not to pose a safety risk). 9. History of severe cardiovascular or cerebrovascular diseases.
- 10. Severe gastrointestinal disease or gastrointestinal dysfunction that may alter the absorption, metabolism or excretion of the study drug; eligibility will be determined by investigator assessment (including but not limited to total gastrectomy, short bowel syndrome, etc.).
- 11. Bleeding disorders, thrombotic disorders, or therapeutic anticoagulation requiring INR monitoring, such as warfarin or any other coumarin derivative anticoagulants.
- 12. Use of strong CYP3A4 inhibitors and other agents that may affect the metabolism of the study drug within <=2 weeks or 5 half-lives (whichever is shorter) prior to study treatment initiation. Other agents that may affect the concomitant medications are as follows: (1) Participants receiving enzalutamide combination therapy: use of strong CYP2C8 inhibitors; (2) Participants receiving darolutamide combination therapy: use of rosuvastatin, strong P-gp inhibitors and inducers.
- 13. Positive human immunodeficiency virus (HIV) test. 14. Active HBV infection (abnormal HBV serology other than positive hepatitis B surface antibody; HBV DNA copy number testing is required to confirm activity) and/or HCV infection (HCV RNA copy number testing is required to confirm activity if HCV antibody is positive).
- 15. Inability to swallow or tolerate oral medication. 16. Other conditions judged by the investigator to make the participant unsuitable for study participation.
Trial locations and contacts
16 sites in 1 country. Contact the study team or a site near you to ask about taking part.
16 sites in 1 country
China16 sites, 16 recruiting
- Not yet recruiting
Peking University Third Hospital
Beijing
Zhang
- Not yet recruiting
Sichuan Cancer Hospital
Chengdu, Sichuan
Liao
- Not yet recruiting
Chongqing University Cancer Hospital
Chongqing
Li
- Not yet recruiting
The First Affiliated Hospital of Chongqing Medical University
Chongqing
Wang
- Not yet recruiting
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian
Xue
- Not yet recruiting
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong
Xue
- Not yet recruiting
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong
Lin
- Not yet recruiting
Zhejiang Provincial People's Hospital
Hangzhou, Zhejiang
Zhang
- Not yet recruiting
The First Hospital of Jiaxing
Jiaxing, Zhejiang
He
- Not yet recruiting
Shandong Cancer Hospital and Institute, Shandong First Medical University
Jinan, Shandong
Bian
- Recruiting
Affiliated Drum Tower Hospital, Medical School of Nanjing University
Nanjing, Jiangsu
Guo
- Not yet recruiting
Nantong Cancer Hospital
Nantong, Jiangsu
Wang
- Not yet recruiting
The First Affiliated Hospital of Ningbo University
Ningbo, Zhejiang
Ma
- Not yet recruiting
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang
Chen
- Not yet recruiting
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Wang
- Not yet recruiting
Zhongnan Hospital of Wuhan University
Wuhan, Hubei
Yu
About this study
Official title: An Open-label, Multicenter, Phase II Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of TT00420 Tablets Combined With Novel Endocrine Therapy in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Progressing After Prior Treatment
The goal of this clinical trial is to learn if tinengotinib combined with darolutamide or enzalutamide works to treat participants with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior androgen receptor pathway inhibitors (ARPIs). It will also learn about the safety of the combination therapy. The main questions it aims to answer are:
- If participants with mCRPC can benefit from the combination therapy of tinengotinib plus one ARPI?
- What medical problems do participants have when taking the combination therapy? Participants will take tinengotinib with darolutamide or enzalutamide to find the optimal dose and regimen of tinengotinib for the combination therapy in stage A. In stage B, participants will take preferred combination regimen of tinengotinib plus darolutamide/enzalutamide identified in stage A. In stage C, researchers will compare selected combination therapy versus standard treatment and/or monotherapy to see if the combination therapy works better.
- Conditions
- Prostate Cancer (CRPC)
- Being tested
- tinengotinib 10 mg QD plus darolutamide, tinengotinib 10 mg QD (2-week on / 1-week off) plus darolutamide, tinengotinib 10 mg QD plus enzalutamide, preferred combination regimen of tinengotinib plus one ARPI, selected combination regimen of tinengotinib plus one ARPI
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tinengotinib 10 mg QD plus darolutamideDrug
Participants will receive tinengotinib 10 mg once daily with darolutamide in 21-day cycles per protocol defined schedule.
tinengotinib 10 mg QD (2-week on / 1-week off) plus darolutamideDrug
Participants will receive tinengotinib 10 mg once daily (2-week on / 1-week off) with darolutamide in 21-day cycles per protocol defined schedule.
tinengotinib 10 mg QD plus enzalutamideDrug
Participants will receive tinengotinib 10 mg once daily with enzalutamide in 21-day cycles per protocol defined schedule.
preferred combination regimen of tinengotinib plus one ARPIDrug
Participants will receive preferred combination regimen of tinengotinib at optimized dose plus one ARPI in 21-day cycles per protocol defined schedule.
selected combination regimen of tinengotinib plus one ARPIDrug
Participants will receive selected combination regimen of tinengotinib at optimized dose plus one ARPI in 21-day cycles per protocol defined schedule.
Darolutamide 600 mg twice dailyDrug
Participants will receive darolutamide 600 mg twice daily in 21-day cycles per protocol defined schedule.
Enzalutamide 160mg daily (oral)Drug
Participants will receive enzalutamide 160mg daily (oral) in 21-day cycles per protocol defined schedule.
| Study group | Role | What they receive |
|---|---|---|
| Stage A (tinengotinib plus darolutamide) | Experimental | Not described Receives: Drug: tinengotinib 10 mg QD plus darolutamide |
| Stage A (tinengotinib (2-week on / 1-week off) plus darolutamide) | Experimental | Not described Receives: Drug: tinengotinib 10 mg QD (2-week on / 1-week off) plus darolutamide |
| Stage A (tinengotinib plus enzalutamide) | Experimental | Not described Receives: Drug: tinengotinib 10 mg QD plus enzalutamide |
| Stage B (combination therapy) | Experimental | optimized combination regimen Receives: Drug: preferred combination regimen of tinengotinib plus one ARPI |
| Stage C (combination therapy) | Experimental | selected combination regimen Receives: Drug: selected combination regimen of tinengotinib plus one ARPI |
| Stage C (ARPI monotherapy therapy) | Active comparator | Not described Receives: Drug: Darolutamide 600 mg twice daily |
| Stage C (physician choice) | Active comparator | Not described Receives: Drug: Enzalutamide 160mg daily (oral) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage A: safety evaluation parameters
Including dose-limiting toxicities (DLTs), and incidence, duration, and severity of other adverse events (AEs)
Measured: From signing of the informed consent until 28 days after the last dose or the end of the study (whichever occurs first), an average of 1 year.
Stage B: 6-month PFS rate (6mo-PFS)
The proportion of patients who remain alive without disease progression at 6 months after study treatment initiation. Tumor assessments are based on RECIST v1.1 and/or PCWG3.
Measured: From first study drug administration to the end of treatment, an average of 1 year.
Stage C: Radiographic progression-free survival (rPFS）
The time from randomization or treatment initiation to the first documented radiographic disease progression or death from any cause, whichever occurs first. Tumor assessments are based on RECIST v1.1 and/or PCWG3.
Measured: From first study drug administration to the end of treatment, an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2026
- Study start18 Sep 2026
- Primary completion31 Dec 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate Cancer (CRPC)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 182 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TransThera Sciences (Nanjing), Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07871110
- Sponsor's protocol ID
- TT00420CN21
- Status last verified
- Oct 2026
- First submitted
- 3 Oct 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No