AMO959 for PSMA-positive metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- Signed informed consent must be obtained prior to participation in the study.\n- Participants must be adults ≥ 18 years of age.\n- Participants must have an ECOG performance status of 0 to 2.\n- Participants must have histologically confirmed adenocarcinoma of the prostate. Participants with other histology (e.g. neuroendocrine, intraductal subtype) are not eligible.\n- Phase Ib: Prior exposure of up to 1 line of taxane-based chemotherapy is permissible. Phase II: Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).\n- Participants must have PSMA-PET positive disease assessed by using a PSMA imaging agent that is approved as per protocol and are eligible as determined by the sponsor’s central reading rules.\n- Castration level of testosterone (< 50 ng/dL]), and/or use of concomitant androgen deprivation therapy ADT\n- 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: •\tSerum/plasma PSA progression is defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression as per PCWG3 guidelines. •\tSoft-tissue progression defined PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016). •\tProgression of bone disease: 2 new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria Scher et al 2016)."}

Exclusion criteria

• {"criterion_text":"- Concurrent local (radiation therapy to the prostate with curative intent or other prostate antineoplastic ablative procedures) or systemic (hormonal ablation, chemotherapy, immunotherapy, XXX RLTs) antineoplastic treatments, or within 28 days of enrollment (Phase Ib) or randomization (Phase II)) or randomization (Phase II)\n- Prior treatment with any RLT or PSMA-targeted agents (approved or investigational)\n- Any other investigational agents within 28 days prior to first dose of any study treatment\n- Concurrent serious medical conditions that may interfere with study procedures or follow-up\n- Participants with a history of CNS metastases must have received therapy (surgery, whole brain radiation therapy, stereotactic radiosurgery) and be neurologically stable, asymptomatic, and not taking corticosteroids for the purpose of maintaining neurologic integrity."}

Primary endpoints

• {"endpoint_text":"- Incidence of dose limiting toxicities (DLTs) with AMO959 in combination with AAA617 +/- ARPI during the first cycle (42 days from first dose of AAA617) of combination treatment\n- Safety: Type, incidence and severity of AEs and SAEs, changes in laboratory values, and vital signs, and deaths\n- Tolerability: Incidence of dose interruptions, reductions, and discontinuation; dose intensity and duration of exposure\n- 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.","definition_or_measurement_approach":"DLTs: incidence during first cycle (42 days from first dose of AAA617). Safety: evaluated by type, incidence and severity of AEs and SAEs, lab changes, vital signs, and deaths. Tolerability: measured by incidence of dose interruptions, reductions, discontinuations, dose intensity and duration of exposure. Biochemical response (PSA50): proportion achieving ≥50% PSA decrease from baseline confirmed by a second PSA measurement ≥4 weeks later."}

Secondary endpoints

• {"endpoint_text":"- PSA90 is defined as the proportion of participants who achieved a ≥ 90% decrease 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. Only for Phase Ib: PSA50 defined as above Only for Phase II: PSA50 in the AAA617 + ARPI arm as defined above\n- rPFS: time from start of study treatment/randomization to radiographic PD/death ORR: proportion of participants with CR/PR DCR: proportion of participants with CR, PR, SD, Non-CR/Non-PD DoR: time from CR/PR to PD/death TTSTP: time from randomization to soft tissue PD OS: time from start of study treatment/randomization to death\n- Plasma concentrations of AMO959 over time and derived PK parameters.\n- Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data\n- Time activity curves (TACs) and absorbed radiation doses in selected organs and tumor lesions.\n- Safety: Type, incidence and severity of AEs and SAEs, changes in laboratory values, and vital signs, and deaths. Tolerability: Incidence of dose interruptions, reductions, and discontinuation; dose intensity and duration of exposure.\n- 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) as assessed by BICR using PSMA PET/CT imaging (Seifert et al 2023, Gafita et al 2023) or death due to any cause, whichever occurs first.\n- Change from baseline in FACT-P Prostate Cancer Subscale (PCS) 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.\n- TTSSE defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first.","definition_or_measurement_approach":"PSA90/PSA50: proportion achieving ≥90% (or ≥50%) decrease from baseline confirmed by second PSA ≥4 weeks later. rPFS/rPFS-PET: time from treatment/randomization to radiographic progression or death; rPFS-PET defined by ≥20% increase in PSMA-positive tumor volume and new PSMA-positive lesions assessed by BICR using PSMA PET/CT. ORR/DCR/DoR/TTSTP/OS: standard time-to-event and response proportion measures as described. PK endpoints: plasma concentrations over time and derived parameters; AAA617 PK from blood radioactivity data. Dosimetry: TACs and absorbed doses in organs and tumors. HRQoL/PROs: change from baseline in FACT-P PCS and time to worsening on BPI-SF Worst Pain. TTSSE: time from randomization to first symptomatic skeletal event as defined."}

France

Earliest CTIS Part Ii Submission Date

19-12-2025

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

76

Number Of Sites

7

Number Of Participants

19

Germany

Earliest CTIS Part Ii Submission Date

12-02-2026

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

21

Number Of Sites

4

Number Of Participants

19

Italy

Earliest CTIS Part Ii Submission Date

12-02-2026

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

26

Number Of Sites

3

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

12-02-2026

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

22

Number Of Sites

4

Number Of Participants

23

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Syneos Health Inc.

Name

IQVIA Limited

Responsibilities

Randomization of participants. Management of drug supply logistics, dispensing and unblinding.

Name

Icon Clinical Research Limited

Name

Parexel International (IRL) Limited

Name

Veeda Clinical Research Limited

Responsibilities

Pharmacokinetics (PK) analysis.

Name

Bioclinica Inc.

Responsibilities

Imaging collection (PET, conventional imaging – CT, MRI, Bone scan, etc.), QC and central eligibility & efficacy review Dosimetry analysis (SPECT)

Third parties

• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Drug distribution, storage, relabeling, return and destruction","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Preparation and distribution of patient engagement materials","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Advanced Accelerator Applications Molecular Imaging Iberica S.L.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Randomization of participants. Management of drug supply logistics, dispensing and unblinding.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient reimbursement.","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging collection (PET, conventional imaging – CT, MRI, Bone scan, etc.), QC and central eligibility & efficacy review Dosimetry analysis (SPECT)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Sample storage and management. Provision of sample collection kits. Biomarker and PK sample storage and onward shipment to the 3rd party lab.","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"Pharmacokinetics (PK) analysis.","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Kayentis","duties_or_roles":"PRO management and data collection via tablet.","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Actigraph LLC","duties_or_roles":"Wrist-worn monitors for documenting physical movement. The devices are intended to monitor activity during sleep and can be used to analyze circadian rhythms.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"PRO licensing, formatting and translations.","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Advanced Accelerator Applications Molecular Imaging Iberica S.L.","duties_or_roles":"Drug/product sourcing and related activities","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Database management and quality control","organisation_type":"Non-Pharmaceutical company"}