A Phase 1/2 interventional study of AMO959 and AAA617 in PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With Prior Exposure to One Prior ARPI Who Are Candidates for Taxane-based Chemotherapy, sponsored by Novartis Pharmaceuticals. Recruiting at 25 sites in 7 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-15.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 1/2, Interventional, and Treatment
The purpose of this phase Ib/II study is to (a) in Phase Ib evaluate the safety, tolerability, and pharmacokinetics (PK) of AMO959 when given in combination with lutetium (177Lu) vipivotide tetraxetan (also known as [177Lu]Lu-PSMA-617 or 177Lu-PSMA-617 and hereafter referred to as AAA617) with an androgen receptor pathway inhibitor (ARPI) in participants with metastatic castration resistant prostate cancer (mCRPC) who have failed one prior ARPI and with or without prior taxane exposure, and (b) in Phase II evaluate the preliminary efficacy of AMO959 in combination with AAA617 and ARPI in participants with mCRPC who have failed one prior ARPI, but who have not yet been exposed to taxane treatment.
This study will consist of two phases:
7,046 studies on the registry are indexed under Prostatic Neoplasms; 1,580 are open to participants now.
This study's planned enrollment of 123 is above the median of 60 across 5,348 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting as their last treatment (and did not progress on more than one ARPI), based on at least 1 of the following criteria:
Key Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive AMO959 BID for first 14 days followed by AAA617+AMO959 every 6 weeks for a maximum of 6 cycles.
Drug: AMO959 · Radiation: AAA617
Participants will receive AAA617 on day 1 followed by AMO959 BID (days 2-15), repeated every 6 weeks, for a maximum of 6 cycles with an ARPI (abiraterone or enzalutamide) administered continuously starting on day 1.
Drug: AMO959 · Radiation: AAA617 · Drug: Enzalutamide · Drug: Abiraterone
Participants will receive a single dose of AMO959 on Day 1 (fed), followed by 2-day washout, then AMO959 BID (fasted) for 14 days followed by 2-day washout and AAA617+AMO959 (fasted) every 6 weeks for a maximum of 6 cycles.
Drug: AMO959 · Radiation: AAA617
Participants will receive AAA617 on day 1 followed by AMO959 BID (days 2-15), repeated every 6 weeks, for a maximum of 6 cycles with an ARPI (abiraterone or enzalutamide administered continuously starting on day 1.
Drug: AMO959 · Radiation: AAA617 · Drug: Enzalutamide · Drug: Abiraterone
Participants will receive AAA617 on day 1 followed by AMO959 BID (days 2-15), repeated every 6 weeks, for a maximum of 6 cycles with an ARPI (abiraterone or enzalutamide) administered continuously starting on day 1.
Drug: AMO959 · Radiation: AAA617 · Drug: Enzalutamide · Drug: Abiraterone
Participants will receive AAA617 every 6 weeks for a maximum of 6 cycles, with ARPI (abiraterone or enzalutamide) administered continuously starting on day 1.
Radiation: AAA617 · Drug: Enzalutamide · Drug: Abiraterone
DNA Damage Response inhibitor
Also known as: BY1298, BY101298
PSMA-targeted radiopharmaceutical
Also known as: Pluvicto [177Lu]Lu-PSMA-617
Androgen receptor pathway inhibitor
Androgen receptor pathway inhibitor
Phase Ib: Incidence rate of Dose-limiting toxicities (DLTs)
Incidence of dose limiting toxicities (DLTs) with AMO959 in combination with AAA617 +/- ARPI A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the evaluation period and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading.
Time frame: Up to 42 days after the first AAA617 dose administration
Phase Ib: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Time frame: From date of start of study treatment, assessed up to approximately 45 months
Phase Ib: Number of Participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation).
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase Ib: Dose Intensity
Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity).
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase Ib: Duration of exposure to each study drug
Duration of exposure (in months) to each study drug.
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase II: Biochemical Response (PSA50)
Biochemical response (PSA50), defined as the proportion of participants who achieved a ≥ 50% decrease in PSA from baseline at any time during the treatment period prior to start of new anti-cancer therapy that is confirmed by a second PSA measurement ≥ 4 weeks later.
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Prostate Specific Antigen 90 (PSA90) response
PSA90 response is defined as the proportion of participants who have achieved a ≥ 90% decrease in PSA from baseline at any time during the treatment period prior to start of new anti-cancer therapy that is confirmed by a second PSA measurement ≥4 weeks later.
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase Ib: Prostate Specific Antigen 50 (PSA50) response
PSA50 response is defined as the proportion of participants who have achieved a ≥ 50% decrease in PSA from baseline at any time during the treatment period prior to the start of new anti-cancer therapy, confirmed by a second PSA measurement ≥4 weeks later.
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase Ib and Phase II: Radiographic progression-free survival (rPFS)
Radiographic progression- free survival (rPFS) is defined as the time from the date of start of study treatment (Phase Ib) / randomization (Phase II) to the date of first documented radiographic disease progression using conventional imaging and Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 criteria (Scher et al 2016) or death due to any cause, whichever occurs first.
Time frame: From date of start of study treatment (Phase Ib) / randomization (Phase II), assessed up to approximately 24 months
Phase Ib and Phase II: Overall Response Rate (ORR)
Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in soft tissue based on tumor response data and according to PCWG3-modified RECIST v1.1, in the absence of bone progression as per PCWG3.
Time frame: From date of start of study treatment (Phase Ib) / randomization (Phase II), assessed up to approximately 24 months
Phase Ib and Phase II: Disease control rate (DCR)
Disease control rate (DCR) is defined as the proportion of participants with a BOR of confirmed CR or PR, stable disease (SD) or Non-CR/Non- progressive disease (PD) in soft tissue based on tumor response data and according to PCWG3-modified RECIST v1.1, in the absence of bone progression as per PCWG3.
Time frame: From date of start of study treatment (Phase Ib) / randomization (Phase II), assessed up to approximately 24 months
Phase Ib and Phase II: Duration of Response (DoR)
Duration of Response (DoR) is defined as the duration of time between the date of first documented response (CR or PR) according to PCWG3- modified RECIST v1.1, in the absence of bone progression as per PCWG3, based on tumor response data and the date of first documented radiographic progression in soft tissue or death due to any cause, whichever occurs first.
Time frame: From date of start of study treatment (Phase Ib) / randomization (Phase II), assessed up to approximately 24 months
Overall Survival (OS)
Overall Survival (OS) is defined as the time from the date of start of study treatment (Phase Ib) / randomization (Phase II) to the date of death due to any cause.
Time frame: From date of start of study, assessed up to approximately 45 months
Phase II: Time to soft tissue progression (TTSTP)
Time to soft tissue progression (TTSTP) is defined as time from randomization to the date of first documented radiographic soft tissue progression per PCWG3-modified RECIST v1.1.
Time frame: From date of start of study randomization, assessed up to approximately 24 months
Phase Ib: Plasma concentrations of AMO959
AMO959 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels by treatment arms
Time frame: Throughout run-in periods and first cycle with AAA617, assessed up to 6 months
Phase Ib: Plasma concentrations of AAA617
AAA617 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels by treatment arms
Time frame: Throughout treatment periods with AAA617, assessed up to 6 months
Phase Ib: Time activity curves (TACs) for AAA617
Time Activity Curves (TAC) will be generated by plotting concentrations against time.
Time frame: Throughout treatment periods with AAA617, assessed up to 6 months
Phase Ib: Absorbed radiation doses in selected organs and tumor lesions for AAA617
The organ absorbed radiation dose and effective radiation dose will be evaluated.
Time frame: Throughout treatment periods with AAA617, assessed up to 6 months
Phase II: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Time frame: From date of start of study treatment, assessed up to approximately 45 months
Phase II: Number of Participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation).
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase II: Dose Intensity
Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity).
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase II: Duration of exposure to each study drug
Duration of exposure (in months) to each study drug.
Time frame: From date of start of study treatment, assessed up to approximately 24 months
Phase II: Radiographic Progression Free Survival (rPFS) by Positron Emission Tomography (PET) (rPFS-PET)
Radiographic Progression Free Survival (rPFS) by Positron Emission Tomography (PET) (rPFS- PET) is defined as the time from the date of randomization to first documented radiographic disease progression (an increase in PSMA-positive tumor volume ≥ 20% from baseline and new PSMA-positive malignant lesions) using PSMA PET/CT imaging (Seifert et al 2023, Gafita et al 2023) or death due to any cause, whichever occurs first.
Time frame: From date of start of study randomization, assessed up to approximately 24 months
Phase II: Change from baseline in FACT-P Prostate Cancer Subscale (PCS)
Change from baseline in FACT-P PCS refers to the difference in a patient's score on the Prostate Cancer Subscale (PCS) of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire between the start of a study (baseline) and subsequent time points.
Time frame: From date of start of study, assessed up to approximately 45 months.
Phase II: Time to worsening on the Brief Pain Inventory - Short Form (BPI-SF)
Time to worsening on the Worst Pain defined as the time from the date of randomization to the first occurrence of worsening on the Brief Pain Inventory - Short Form (BPI-SF) Worst Pain item of at least 30% increase from baseline or a minimum of 2 points increase from baseline or death due to any cause, whichever occurs first.
Time frame: From date of start of study, assessed up to approximately 45 months.
Phase II: Time to first symptomatic skeletal event (TTSSE)
Time to first symptomatic skeletal event (TTSSE) is defined as the time from the date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurs first.
Time frame: From date of start of study randomization, assessed up to approximately 24 months.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
No publications or documents are linked to this record.
Started Dec 2025 (actual). Primary completion is estimated for Jul 2028, 31 months after the start.
Of 96 industry-sponsored phase 1/2 interventional studies under Prostatic Neoplasms, half reached primary completion within 52 months of starting (the median), counting those still running; a quarter within 35. This study's planned 31 months is below that.
Counting every sponsor, half of 210 studies reached it within 61 months; a quarter within 30 and three quarters within 85.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Enzalutamide · Abiraterone