A Phase 1b/2 Study Evaluating the Activity of Tinengotinib (TT–00420) in Combination with Androgen Receptor Signaling Inhibitors (ARSIs) in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

You are being asked to take part in this study because you have a type of prostate cancer called metastatic castration-resistant prostate cancer (mCRPC), meaning that your disease has spread to other parts of your body (metastatic). The purpose of this study is to determine whether adding the experimental drug tinengotinib, which is not yet approved by the United States Food and Drug Administration (FDA), to your standard treatment is safe, effective, and produces minimal or mild side effects in individuals with mCRPC. Additionally, we will evaluate the effectiveness of tinengotinib in combination with abiraterone acetate and prednisone or enzalutamide against participants’ cancer. The study will test the highest tolerable dose of tinengotinib, as identified in previous research, to confirm the optimal dose for further investigation. Researchers believe that combining tinengotinib with standard treatments—abiraterone acetate, prednisone, or enzalutamide—may benefit individuals with your condition. Tinengotinib works by inhibiting several proteins involved in cancer cell growth and survival, which may help slow or halt the progression of your cancer. Abiraterone acetate decreases the activity of reproductive hormones (androgens). Androgens stimulate prostate cancer cells to grow. By decreasing the activity of androgens, abiraterone acetate may help slow or stop the growth of prostate cancer cells. Prednisone is given with abiraterone acetate to reduce or prevent some of the side effects of abiraterone acetate. Enzalutamide is a type of drug called an androgen receptor (AR) inhibitor. It works by blocking the effects of androgen, which helps stop the growth and spread of cancer cells.

Are you Eligible? (Inclusion Criteria)

• Participants ≥ 18 years old, with signed informed consent 2. Tumor biopsy during screening is required if safe and feasible. 3. Histologically confirmed carcinoma of the prostate (neuroendocrine differentiation is allowed, but pure small cell carcinoma is not permitted)