Advanced Physician Search: 3rd Line Therapy

The purpose of this study is to find out whether treatment with pasritamig and docetaxel prolongs radiographic progression free survival (rPFS) (the length of time from start of treatment until disease worsens as determined by scans or death due to any cause) when compared to treatment with docetaxel in participants with metastatic castrate-resistant prostate cancer (mCRPC; a cancer of prostate, a male reproductive gland found below the bladder, that grows despite low levels of male hormones).

Drug: Docetaxel, Drug: Prednisone/Prednisolone

This phase II trial evaluates whether genetic testing in prostate cancer is helpful in deciding which study treatment patients are assigned. Patient cancer tissue samples are obtained from a previous surgery or biopsy procedure and tested for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) abnormalities or mutations in their cancer. Valemetostat tosylate is in a class of medications called EZH1/EZH2 inhibitors. It blocks proteins called EZH1 and EZH2, which may help slow or stop the spread of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Cabazitaxel injection is in a class of medications called microtubule inhibitors. It works by slowing or stopping the growth of tumor cells. Abiraterone acetate blocks tissues from making androgens (male hormones), such as testosterone. This may cause the death of tumor cells that need androgens to grow. It is a type of anti-androgen. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Lutetium Lu 177 vipivotide tetraxetan is in a class of medications called radiopharmaceuticals. It works by targeting and delivering radiation directly to tumor cells which damages and kills these cells. Assigning patients to targeted treatment based on genetic testing may help shrink or slow the cancer from growing

Other: Genetic testing, Procedure: Magnetic Resonance Imaging, Procedure: Computed Tomography, Procedure: Bone scan, Procedure: FDG-Positron Emission Tomography, Procedure: PSMA PET Scan, Procedure: Biospecimen Collection, Drug: Cabazitaxel, Drug: Abiraterone Acetate, Drug: Enzalutamide, Drug: Lutetium Lu 177 Vipivotide Tetraxetan

The purpose of this study is to determine whether [225Ac]Ac-PSMA-617 (AAA817), given for up to 6 cycles at a dose of 10 Megabecquerel (MBq) +/- 10%, plus androgen receptor pathway inhibitor (ARPI), improves the radiographic progression free survival (rPFS) compared to investigator’s choice of standard of care (SOC) (ARPI change or taxane-based chemotherapy or [177Lu]Lu-PSMA-617 (AAA617)) in adult participants with PSMA-positive metastatic castration resistant prostate cancer (mCRPC) treated with another ARPI as last treatment and who have not been exposed to a taxane-containing chemotherapy in the mCRPC setting nor have received any prior PSMA-targeting radioligand therapy.

Drug: ARPI, Drug: Standard of Care

This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after [177Lu]Lu-PSMA targeted therapy. Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator’s choice of Standard of Care, regardless of subsequent anti-neoplastic treatment

Drug: AAA817

This phase III trial compares the effect of adding carboplatin to the standard of care chemotherapy drug cabazitaxel versus cabazitaxel alone in treating prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels (castrate-resistant) and that has spread from where it first started (primary site) to other places in the body (metastatic). Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Chemotherapy drugs, such as cabazitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Prednisone is often given together with chemotherapy drugs. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body’s immune response to help lessen the side effects of chemotherapy drugs and to help the chemotherapy work. Giving carboplatin with the standard of care chemotherapy drug cabazitaxel may be better at treating metastatic castrate-resistant prostate cancer.

Procedure: Biospecimen Collection, Procedure: Bone Scan, Drug: Cabazitaxel, Drug: Carboplatin, Procedure: Chest Radiography, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission Tomography, Drug: Prednisone

This is a four-part study evaluating the safety and efficacy of a PSMA-directed radioantibody (rosopatamab tetraxetan, conjugated to either In-111 or Ac-225). Part 1 will consist of one administration of In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants then will be enrolled into either Part 2 (Dose Optimization) or Part 3 (Dose Escalation and Expansion) depending on their prior treatment history. Part 4 will be an extended regimen in dose escalation and expansion. Participants qualifying for Part 2 will be randomized to receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle (dose administration on Day 1 and Day 15) at either 45 or 60 kBq/Kg. Participants qualifying for Part 3 must have received prior Lu-177-PSMA-radioligand therapy and will receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle at 45, 55, or 60 kBq/Kg. Dose limiting toxicities (DLTs) will be monitored in Part 3 to determine the recommended phase 2 dose (RP2D), and the study may enroll additional participants to be treated with the RP2D dose level. Participants qualifying for Part 4 will initially receive two doses (dose administration on Day 1 and Day 15) at the dose level selected in Part 2, followed by a single third dose of Ac-225 rosopatamab tetraxetan administered approximately 12 weeks after completion of the Part 2 fractionated dosing regimen. The starting dose level for Part 4 will be 22 kBq/kg (or fixed activity equivalent). Dose limiting toxicities (DLTs) will be monitored following administration of the third dose in Part 4 to determine the recommended phase 2 dose (RP2D) of a third dose of Ac-225 rosopatamab tetraxetan. Participants enrolled into any part will attend study visits which will include blood samples, electrocardiogram (ECG), radiographic imaging, and physical examinations along with other assessments.

Biological: Single dose 22 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan, Biological: Single dose 34 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan, Biological: Single dose 45 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan

This study is a first-in-human, Phase 1, open-label, multicenter study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and the preliminary efficacy of JANX007 in adults with metastatic castration-resistant prostate cancer (mCRPC).

Biological: JANX007, Drug: Darolutamide

This phase I/II trial studies the best dose of M3814 when given together with radium-223 dichloride or with radium-223 dichloride and avelumab and to see how well they work in treating patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as radium-223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to find out the better treatment between radium-223 dichloride alone, radium-223 dichloride in combination with M3814, or radium-223 dichloride in combination with both M3814 and avelumab, to lower the chance of prostate cancer growing or spreading in the bone, and if this approach is better or worse than the usual approach for advanced prostate cancer not responsive to hormonal therapy.

Drug: Avelumab, Procedure: Biospecimen Collection, Procedure: Bone Scan, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Drug: Peposertib, Other: Questionnaire Administration, Radiation: Radium Ra 223 Dichloride