GOZETOTIDE for Metastatic hormone-sensitive prostate cancer (mHSPC) | PSMA-positive metastatic hormone-sensitive prostate cancer

Inclusion criteria

• {"criterion_text":"- Signed informed consent must be obtained prior to participation in the study\n- Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial\n- Patients must be: Treatment naïve OR minimally treated with: • Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation antiandrogen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation antiandrogen must be discontinued prior to start of study therapy or after 45 days whatever happens first. • If received, prior LHRH agonist/antagonist with or without first generation antiandrogen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy. • Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. • No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.\n- Patients must be adults ≥18 years of age\n- Patients must have an ECOG performance status of 0 to 2\n- Patients must have a life expectancy >9 months as determined by the study investigator\n- Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)\n- Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor’s central reader\n- Patients must have at least one metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization: a. Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/ OR b. Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/ OR c. Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).\n- Patients must have adequate organ function: • Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL • Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN), for patients with known Gilbert’s Syndrome ≤3 x ULN is permitted. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases • Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation\n- Albumin ≥2.5 g/dL"}

Exclusion criteria

• {"criterion_text":"- Patients with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy\n- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.\n- Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance)\n- Active clinically significant cardiac disease defined as any of the following: • NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3. • History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventicular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block) • History of familial long QT syndrome or known family history of Torsades of Pointes • Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature\n- History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study\n- Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression\n- Inability to complete the study imaging procedures due to any reason (e.g., severe claustrophobia, inability to lie still for the entire imaging time, any condition that precludes raised arms position)\n- Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: patients with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.\n- Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF\n- Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).\n- Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy\n- Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed\n- Ongoing participation in any other clinical trial\n- Use of other investigational drugs within 30 days prior to day of randomization\n- Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes\n- Transfusion for the sole purpose of making a participant eligible for study inclusion\n- Participant with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participant with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Patients with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed; baseline and subsequent radiological imaging for them must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast)."}

Primary endpoints

• {"endpoint_text":"- Radiographic progression-free survival (rPFS) is defined as the time from the date of randomization to the date of first documented radiographic disease progression as assessed by blinded independent central review (BIRC) and as outlined in Prostate Cancer Working Group 3 (PCWG3) Guidelines (Scher et al 2016) or death due to any cause","definition_or_measurement_approach":"Time from randomization to first documented radiographic progression as assessed by Blinded Independent Review Committee (BIRC) following PCWG3 guidelines, or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- Overall survival is defined as the time from the date of randomization to the date of death due to any cause","definition_or_measurement_approach":"Time from randomization to death due to any cause."}
• {"endpoint_text":"- PSA90 response is defined as the proportion of patients who have a ≥90% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement ≥4 weeks later. PSA90 at 12, 24 and 48 weeks will be evaluated.","definition_or_measurement_approach":"Proportion of patients with ≥90% decrease in PSA from baseline confirmed by a subsequent PSA measurement ≥4 weeks later; evaluated at weeks 12, 24 and 48."}
• {"endpoint_text":"- Time to development of mCRPC is defined as the time from date of randomization to disease progression despite androgen deprivation therapy (ADT) presenting as either a continuous rise in serum prostate specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.","definition_or_measurement_approach":"Time from randomization to progression despite ADT manifested by continuous rise in PSA, progression of existing disease, or new metastases."}
• {"endpoint_text":"- PFS is defined as the time from date of randomization to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first","definition_or_measurement_approach":"Investigator-assessed time from randomization to first documented progression (radiographic, clinical, or PSA) or death."}
• {"endpoint_text":"- PFS2 is defined as time from date of randomization to the first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) on next-line therapy or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Time from randomization to first documented progression on next-line therapy by investigator assessment or death."}
• {"endpoint_text":"- Proportion of patients with PSA < 0.2 ng/mL at 12, 24 and 48 weeks","definition_or_measurement_approach":"Proportion of patients achieving PSA <0.2 ng/mL at specified timepoints (12, 24, 48 weeks)."}
• {"endpoint_text":"- ORR, DCR, TTR, DOR, TTSTP based on PCWG3- modified RECIST 1.1 by BIRC.","definition_or_measurement_approach":"Objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), time to soft tissue progression (TTSTP) assessed by BIRC using PCWG3-modified RECIST v1.1."}
• {"endpoint_text":"- Safety: incidence and severity of AEs and serious adverse event (SAE)s, changes in laboratory values, vital signs and ECGs. Any clinically significant lab, vital signs, ECG abnormalities will be captured as an AE.","definition_or_measurement_approach":"Safety evaluated by incidence/severity of AEs/SAEs, laboratory changes, vital signs and ECG abnormalities; clinically significant abnormalities recorded as AEs."}
• {"endpoint_text":"- Tolerability: dose interruptions, reductions and dose intensity","definition_or_measurement_approach":"Tolerability evaluated by monitoring dose interruptions, dose reductions, and dose intensity."}
• {"endpoint_text":"- HRQoL as assessed by Functional Assessment of Cancer Therapy Prostate (FACT-P), Brief Pain Inventory (Short Form (BPI-SF) and European Quality of Life (EuroQol) 5 Domain 5 Level scale (EQ-5D-5L)","definition_or_measurement_approach":"Health-related quality of life measured using FACT-P, BPI-SF, and EQ-5D-5L instruments."}
• {"endpoint_text":"- Time to SSE (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":"Time from randomization to first symptomatic skeletal event (pathological fracture, spinal cord compression, tumor-related orthopedic surgery, palliative radiotherapy to bone pain) or death."}

Poland

Earliest CTIS Part Ii Submission Date

05-02-2024

Latest Decision Or Authorization Date

05-09-2025

Number Of Sites

3

Number Of Participants

32

Germany

Earliest CTIS Part Ii Submission Date

31-01-2024

Latest Decision Or Authorization Date

10-09-2025

Number Of Sites

6

Number Of Participants

49

Netherlands

Earliest CTIS Part Ii Submission Date

31-01-2024

Latest Decision Or Authorization Date

08-09-2025

Number Of Sites

4

Number Of Participants

27

Denmark

Earliest CTIS Part Ii Submission Date

30-01-2024

Latest Decision Or Authorization Date

08-09-2025

Number Of Sites

1

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

31-01-2024

Latest Decision Or Authorization Date

09-09-2025

Number Of Sites

11

Number Of Participants

135

France

Earliest CTIS Part Ii Submission Date

30-01-2024

Latest Decision Or Authorization Date

04-12-2025

Number Of Sites

11

Number Of Participants

109

Belgium

Earliest CTIS Part Ii Submission Date

01-02-2024

Latest Decision Or Authorization Date

16-12-2025

Number Of Sites

2

Number Of Participants

11

Czechia

Earliest CTIS Part Ii Submission Date

01-02-2024

Latest Decision Or Authorization Date

01-12-2025

Number Of Sites

2

Number Of Participants

18

Sweden

Earliest CTIS Part Ii Submission Date

05-02-2024

Latest Decision Or Authorization Date

26-01-2026

Number Of Sites

3

Number Of Participants

17

Austria

Earliest CTIS Part Ii Submission Date

07-03-2024

Latest Decision Or Authorization Date

24-03-2026

Number Of Sites

3

Number Of Participants

43

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Syneos Health Clinical Spain S.L.

Responsibilities

code 1

Name

Syneos Health Inc.

Responsibilities

code 1

Name

IQVIA RDS Spain S.L.

Responsibilities

code 1

Name

IQVIA Limited

Responsibilities

code 1

Name

IQVIA RDS (India) Private Limited

Responsibilities

code 3

Name

Parexel International (IRL) Limited

Responsibilities

code 12

Name

Icon Clinical Research Limited

Responsibilities

code 1

Name

Rps Research Iberica S.L.

Responsibilities

code 1

Name

Bioclinica Inc.

Responsibilities

codes 11,13,5,6,7

Name

Kayentis

Responsibilities

codes 5,6,7

Third parties

• {"country":"Spain","full_name":"Advanced Accelerator Applications Molecular Imaging Iberica S.L.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Syneos Health Clinical Spain S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Eco-Abc Sp. z o. o.","duties_or_roles":"Destruction of the investigational medicinal products","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Advanced Accelerator Applications Iberica S.L.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"Vseobecna Fakultni Nemocnice V Praze","duties_or_roles":"68Ga-PSMA-11 preparation and administration, diagnostic via PET/CT","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Poland","full_name":"Centrala Farmaceutyczna Cefarm S.A.","duties_or_roles":"Drug (IMP/ non-IMP) labeling/relabeling","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Kayentis","duties_or_roles":"codes 5,6,7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"IQVIA RDS Spain S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Rps Research Iberica S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"code 12","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Komtur Polska Sp. z o.o.","duties_or_roles":"Local purchase of medicinal products (IMP & non-IMP)","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"IQVIA RDS (India) Private Limited","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Curium Pharma Spain S.A.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"codes 11,13,5,6,7","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Drug destruction","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Statmed Sp. z o.o.","duties_or_roles":"Compensation for patients travel to the clinical site","organisation_type":"Pharmaceutical company"}