Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Lung Neoplasms

Squamous Cell Carcinoma of Head and Neck

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Antibodies, Bispecific

Immunoglobulins

Mitogens

Chelating Agents

Radiopharmaceuticals

The study conducted in two parts: Part A Dose Exploration and Part B Dose Escalation

FPI-2053 dose exploration to determine the optimal pre-dose administration of FPI-2053 with a fixed dose of \[225Ac\]-FPI-2068.

\[225Ac\]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A.

FPI-2053 is a bispecific antibody that targets EGFR and cMET

FPI-2053

\[111In\]-FPI-2107 is an imaging agent in which indium-111 is conjugated to FPI-2053.

Participants will have a fixed dose of \[111In\]-FPI-2107 followed by imaging scans (with or without pre-administration of FPI-2053).

[111In]-FPI-2107

\[225Ac\]-FPI-2068 is a radiopharmaceutical therapy in which an alpha emitter, actinium-225, is conjugated to FPI-2053.

Participants will be dosed through IV administration every 56 days for up to 3 cycles of the Treatment Period.

[225Ac]-FPI-2068

Clinical Trials Fusion Pharmaceuticals Clinical Operations

David Marcellus

Andrei Iagaru, MD

Aditya Juloori, MD

Veronika Seseri

Heather Jacene, MD

Kristen Harrington

Richard Wahl, MD

John Crandall

Jordi Rodon Ahnert, MD

Yang Lu, MD

Delphine Chen, MD

Heather White

Daniel Juneau, MD

Michel Pavic, MD

Christine Lawson

Éric Turcotte, MD

Lisa Jean-Louis

This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of \[225Ac\]-FPI-2068, \[111In\]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC).

The study will be conducted in 2 parts:

Part A: optimization of the FPI-2053 dose (treatment with dose level 1 of \[225Ac\]-FPI-2068 - fixed dose).

Part B: dose escalation of \[225Ac\]-FPI-2068 with optimal FPI-2053. Part B will commence once the optimal dose of FPI-2053 is determined in Part A. The RP2D will be determined from Part B based on all available safety, efficacy, PK, and dosimetry information.

A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

A Phase 1, First-in-human, Multicentre, Open-label, Dose Escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

• Incidence of Adverse Events and evaluation of dosimetry

* For Part A, evaluate the impact of pre-dose administration of FPI-2053 on the radiation dosimetry of \[111In\]-FPI-2107 (whole body, organs, and selected regions of interest)
* Estimate the effect of pre-dose administration of FPI-2053 on the radiation dosimetry of \[225Ac\]-FPI-2068 (whole body, organs, and selected regions of interest)

Determine the RP2D of \[225Ac\]-FPI-2068, given with or without FPI-2053

• Tumour assessments will be based on RECIST v1.1 (Eisenhauer et al, 2009) and will be performed approximately every 8 weeks (± 1 week) after the first \[225Ac\]-FPI-2068 dose, or as clinically indicated.

• Tumor uptake of \[111In\]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images

• Determine the plasma concentrations and PK parameters of \[111In\]-FPI-2107, and \[225Ac\]-FPI-2068 and the effect of pre-dose administration of FPI-2053 on the plasma concentrations and PK parameters of \[111In\]-FPI-2107.

• Presence of ADA for \[111In\]-FPI-2107, \[225Ac\]-FPI-2068, and FPI-2053

AstraZeneca

Fusion Pharmaceuticals Inc.

Gland and Hormone Related Diseases

Rare Diseases

Stomach Neoplasms

Esophageal Neoplasms

Pancreatic Neoplasms

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Stomach Cancer

Esophageal Cancer

Pancreatic Cancer

Neuroepithelioma

Pharmaceutical Solutions

Patients will receive 68Ga-FF58 and only patients with tumor uptake of 68Ga-FF58 will receive 177Lu-FF58.

Kit for radiopharmaceutical preparation of 68Ga- FF58 solution for injection

68Ga-FF58

177Lu-FF58

Novartis Pharmaceuticals

Ashley O Meara

Shadi Abdar Esfahani

The purpose of the study is to test the safety and dosing of \[177Lu\]Lu-FF58, a radioligand therapy for patients with advanced or metastatic tumors that express proteins known as integrins: alpha-v beta-3 integrin (αvβ3) and alpha-v beta-5 integrin (αvβ5). The study will also further characterize the radioligand imaging agent \[68Ga\]Ga-FF58 including its ability to identify tumor lesions and its safety profile.

The study will be done in two parts. The first part is called "escalation" and the second part is called "expansion". In both parts of the study, patients will be screened with a \[68Ga\]Ga-FF58 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan to assess eligibility for treatment with \[177Lu\]Lu-FF58. In the escalation part, different doses of \[177Lu\]Lu-FF58 will be tested to identify the recommended dose. The expansion part of the study will examine the safety and preliminary efficacy of \[177Lu\]Lu-FF58 at the recommended dose determined during the escalation part. The end of study will occur when at least 80% of the patients in the expansion part have completed the follow-up for disease progression or discontinued from the study for any reason, and all patients have completed treatment and the 36 month long term follow- up period, or the study is terminated early in which case all patients would also be followed up for safety.

A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors.

A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry and Preliminary Activity of [177Lu]Lu-FF58 in Patients With Selected Advanced Solid Tumors.

A dose limiting toxicity (DLT) is defined as any AE or abnormal laboratory value of CTCAE (v5.0) Grade 3 or higher that occurs within the DLT evaluation period (i.e., 6 weeks starting from the first administration of 177Lu-FF58) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications.

The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

Dose modifications (dose interruptions and reductions) for 177Lu-FF58 will be assessed and summarized using descriptive statistics. The number of patients with dose modification and the reasons will be summarized by treatment groups.

Dose intensity for 177Lu-FF58 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.

ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI using FAS.

DOR is the time between the first documented response (CR or PR) and the date of progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause. Here, death due to any cause is considered as an event to be conservative and align with PFS event definition. DOR may be presented graphically if enough events are available for analysis, using Kaplan Meier plots for all patients who achieved a CR/PR in the study. The median DOR and corresponding 90% CI will be presented. Analysis will include responders with confirmed responses.

DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI, using FAS.

PFS is defined as the time from the date of start of treatment to the date of the first documented progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUC from time zero to specified time point (mass x time x volume-1) will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The total body clearance of drug from the plasma (volume x time-1) will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics.

Urine samples will be collected over specified time intervals and analysed for radioactivity. The radioactivity excreted in each interval as a percentage of injected activity (%IA) will be listed and summarized using descriptive statistics.

Time-activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%IA/g) as a function of time.

The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.

After 68Ga-FF58 administration, 68Ga-FF58 PET/CT or PET/MRI will be performed. The statistical analyses of imaging properties of 68Ga-FF58 will be descriptive in nature and will include summaries and graphical presentations of data. No formal testing will be performed.

Symptoms and General Pathology

Recurrence

Antineoplastic Agents

Temozolomide

Lutetium Lu 177 dotatate

1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants with newly diagnosed glioblastoma will receive \[177Lu\]Lu-DOTA-TATE every 4 weeks +/- 2 days, starting 7 to 10 days prior to initiation of Radiotherapy (RT) and Temozolomide (TMZ)

Participants with recurrent glioblastoma will receive \[177Lu\]Lu-DOTA-TATE as single agent therapy every 3 weeks +/- 2 days

Group 1: \[177Lu\]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 4 weeks. Three provisional dose levels (Dose level +2: 250 mCi; Dose level +1: 200 mCi; Dose level -1: 100 mCi) will be assessed.

Group 3: \[177Lu\]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 3 weeks. Three provisional dose levels (Dose level +2: 250 mCi; Dose level +1: 200 mCi; Dose level -1: 100 mCi) will be assessed.

[177Lu]Lu-DOTA-TATE

2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)

[68Ga]Ga-DOTA-TATE

Concomitant Phase: Temozolomide 75mg/m2/d p.o until last day of EBRT.

Maintenance Phase: Temozolomide p.o 150 mg/m2/d during cycle 1 then 200 mg/m2/d for the following cycles if tolerated well in Cycle 1. 6 cycles total (1 cycle = every 28 days)

2 Gy/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks

Radiotherapy

Carolyn Stone

Jan Drappatz

Chetna Wathoo

Nazanin K Majd

Marissa Weiss

Ankush Bhatia

A Dose Finding Study of \[177Lu\]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination with Standard of Care and in Recurrent Glioblastoma as a Single Agent

The study for each participant consists of a Screening period, a Treatment period and a 12-month Follow-up period.

During the screening period of up to 6 weeks before starting GBM treatment, each participant will be assessed for somatostatin receptor (SSTR) expression by \[68Ga\]Ga-DOTA-TATE imaging PET/scan.

Eligible participants with newly diagnosed glioblastoma will be assigned to Group 1 :

• Participants in Group 1 (concomitant radiotherapy + temozolomide and temozolomide maintenance) will receive treatment with \[177Lu\]Lu-DOTA-TATE every 4 weeks +/- 2 days, up to 6 administrations. Radiotherapy and temozolomide will be administered 7 to 10 days after the first administration of \[177Lu\]Lu-DOTA-TATE. Temozolomide will be administered orally at a dose of 75 mg/m2/day during the concomitant period, concurrently with radiotherapy. Radiotherapy will be delivered at a dose of 2 Gray (Gy)/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks with a total dose of 60 Gy (without interruption). During the maintenance period, there is an intra-patient dose escalation in temozolomide treatment. The dosage of temozolomide is 150 mg/m2 in Cycle 1 of maintenance period, and then to 200 mg/m2 in Cycle 2 and beyond in the maintenance period, if 150 mg/m2 temozolomide treatment is well tolerated in Cycle 1.

Eligible participants with recurrent glioblastoma will be assigned to Group 3 and will receive \[177Lu\]Lu-DOTA-TATE as single agent treatment every 3 weeks +/- 2 days.

An infusion of sterile 2.5% Lysine - Arginine amino acid (AA) solution will be co-administered with each \[177Lu\]Lu-DOTA-TATE dose for renal protection.

A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Standard of Care and in Recurrent Glioblastoma as a Single Agent.

A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Radiotherapy With or Without Temozolomide and in Recurrent Glioblastoma as Single Agent

A dose-limiting toxicity (DLT) is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that meets any of the criteria defining dose-limiting toxicities and with an onset during the DLT observation period specified for the group.

• Group 1: DLT observation period of 49 to 52 days starting from the first administration of \[177Lu\]Lu-DOTA-TATE (Day 1) and ending with the completion of concomitant RT and TMZ. The 49 to 52 days observation period is depending on the start day of concomitant RT and TMZ (i.e. 7-10 days post first \[177Lu\]Lu-DOTA-TATE dose). If the concomitant RT and TMZ is delayed for any reason, the DLT observation period will last until the completion of the concomitant treatment. If RT or TMZ is delayed, the DLT observation period will last until the last administered dose, whichever occurs later.

A dose-limiting toxicity (DLT) is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that meets any of the criteria defining dose-limiting toxicities and with an onset during the DLT observation period specified for the group.

• Group 3: DLT observation period of 42 days starting from the first administration of \[177Lu\]Lu-DOTA-TATE (Day 1) i.e. accounting for 2 cycles of Lu\]Lu-DOTA-TATE.

The distribution of adverse events of \[177Lu\]Lu-DOTA-TATE will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

During the follow up period, all AEs and lab abnormalities will be collected within 8 weeks after the last dose of study treatment. For participants with study drug related AEs, they will be followed until resolution or until the End of Study, whichever occurs first. Apart from that, only survival information, SAEs, that are considered related to study drug by the Investigator, and AEs of secondary hematological malignancies will be collected until the end of follow up period every 8 weeks.

The distribution of adverse events of \[68Ga\]Ga-DOTA-TATE will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

According to modified RANO, the objective overall status combines the radiographic response on target lesions, new disease, neurological status and use of steroids and the result is reported as confirmed or preliminary CR, confirmed or preliminary PR, stable disease, confirmed or preliminary disease progression. The best objective overall status achieved during the study will be summarized using frequency and percentage. The rate of confirmed complete or partial response will be summarized using point estimate and 2-sided exact binomial 95% confidence interval (Clopper-Pearson) and presented by dose level within each group.

Progression-Free Survival (PFS) is defined as the time from the date of first dose to the date of confirmed progression according to modified RANO or death due to any cause. If no PFS event is observed, PFS will be censored at the date of the last adequate tumor assessment prior to data cut-off date and start of new anti neoplastic therapy, whichever comes first. PFS will be analyzed in the FAS population and results will be presented for each dose level within each group. The PFS distribution will be estimated using the Kaplan-Meier method.

Overall Survival (OS) is defined as the time from date of first dose to date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date). OS will be analyzed in the FAS population and results will be presented for each dose level within each group. The OS distribution will be estimated using the Kaplan-Meier method.

Time activity curves (TACs), describing percentage (%) of the activity injected vs time in blood, organs and tumor lesions

Absorbed radiation doses of \[177Lu\]Lu-DOTA-TATE in organs and tumor lesions will be summarized with descriptive statistics.

Blood samples for radioactivity measurement will be collected before the start of \[177Lu\]Lu-DOTA-TATE infusion, at the end of \[177Lu\]Lu-DOTA-TATE infusion, then at 2 h, 6 h, 24 h, 48 h and 168 h after the end of \[177Lu\]Lu-DOTA-TATE infusion for participants undergoing dosimetry. Blood samples will be drawn in heparinized tubes. Radioactivity measurements on blood will be performed locally on site, using a gamma-counter.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Tmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUClast will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUCinf will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. CL will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Terminal-Phase Disposition Rate Constant will be listed and summarized using descriptive statistics.

All excreted urine from the start of \[177Lu\]Lu-DOTA-TATE infusion until the first whole body planar imaging will be collected, its volume measured and the radioactivity concentration kilobecquerel per milliliter (kBq/mL) determined in order to calculate the total radioactivity excreted from the body from the start of \[177Lu\]Lu-DOTA-TATE infusion to the time of the first scan. If no urine is excreted from the start of \[177Lu\]Lu-DOTA-TATE infusion until the first whole body planar imaging, no urine dosimetry is necessary.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Kennedy Disease

Gallium 68 PSMA-11

Androgens

Hormones

Pluvicto

Participant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

administered intravenously once every 6 weeks (1 cycle) for 6 cycles

177Lu-PSMA-617

Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD

68Ga-PSMA-11

Administered orally on a continuous basis as per package insert and guideline

ARDT

ADT are administered as per physician order

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study. As of 31-Jan-2024, 1144 participants have been enrolled in 20 countries.

In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment naïve or minimally treated PSMA-positive mHSPC will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

The primary objective of the study is to determine whether the combination of 177Lu-PSMA-617 + SoC improves rPFS over that obtained by administration of SoC alone in mHSPC patients.

The randomization will be stratified according to the following three factors: disease volume (high v low), age \>= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no).

Study duration: approximately 50 months. screening period: after signing ICF, patients will be assessed for eligibility and will be scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant will be randomized via the interactive response technology (IRT) system.

Amended protocol v02 included an option for participants to be enrolled into a separate long-term safety follow-up study, and China extension cohort (40 to 60 participants). Amended protocol v03 excluded China extension cohort and added a second 68Ga-PSMA-11 PET/CT scan at rPD.

Prior treatment:

* Up to 45 days of LHRH agonist/antagonists is allowed prior to ICF signature. If patient did not start the ADT prior randomization, ADT should start as soon as possible and ideally no later than 2 weeks after randomization.
* Up to 45 days of ARDT is allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT should start as soon as possible and ideally no later than 2 weeks after randomization. Patients will received ARDT as per label instructions.

Randomization period:

The participant will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

Treatment period:

Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients will receive SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients must begin 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product is received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles.

Patients randomized to the control arm will begin receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol.

The primary endpoint of rPFS will be assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician.

Participants from both arms will also undergo PET/CT scan with 68GaPSMA-11 following Centrally confirmed rPD.

An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment.

Cross-over period:

After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =\< 7 days and enter the Post-treatment Follow-up .

Post-Treatment Follow-Up (Safety, Efficacy):

After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months.

Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first.

Survival Follow-Up:

After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.

Patient randomized to SOC arm have an option to crossover to 177Lu-PSMA-617 treatment after rPFS

An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC

An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

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

rPFS is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death

OS is defined as time to death for any cause

PSA90 response is defined as the proportion of patients who have a more/equal 90% decrease in PSA from baseline, it will be calculated at 12, 24 and 48 months

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.

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

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.

Proportion of patients with PSA \< 0.2 ng/mL at months 12, 24 and 48 months

TTSTP is defined as time from randomization to radiographic soft tissue progression per PCWG3-modified RECIST v1.1 (Soft Tissue Rules of Prostate Cancer Working Group modified Response Evaluation Criteria in Solid Tumors Version 1.1) as assessed by Blinded Independent Central Review (BICR)

Time to SSE (TTSSE) is 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

ORR is defined as the proportion of participants with best overall response of complete response or partial response in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

DCR is defined as the proportion of participants with best overall response of complete response or partial response or Stable disease in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

DOR is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause

TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours	NCT06147037	Advanced Solid ... Metastatic Colo... Head and Neck S... Non-small Cell ... Pancreatic Duct...	FPI-2053 [111In]-FPI-210... [225Ac]-FPI-206...	18 Years -	Fusion Pharmaceuticals Inc.
A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors.	NCT05977322	Pancreatic Duct... Gastroesophagea... Glioblastoma Mu...	68Ga-FF58 177Lu-FF58	18 Years -	Novartis
A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Standard of Care and in Recurrent Glioblastoma as a Single Agent.	NCT05109728	Glioblastoma	[177Lu]Lu-DOTA-... [68Ga]Ga-DOTA-T... Temozolomide Radiotherapy	18 Years -	Novartis
A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors.	NCT05977322	Pancreatic Duct... Gastroesophagea... Glioblastoma Mu...	68Ga-FF58 177Lu-FF58	18 Years -	Novartis
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC	NCT04720157	Prostatic Neopl...	177Lu-PSMA-617 68Ga-PSMA-11 ARDT ADT	18 Years -	Novartis
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC	NCT04720157	Prostatic Neopl...	177Lu-PSMA-617 68Ga-PSMA-11 ARDT ADT	18 Years -	Novartis
A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Standard of Care and in Recurrent Glioblastoma as a Single Agent.	NCT05109728	Glioblastoma	[177Lu]Lu-DOTA-... [68Ga]Ga-DOTA-T... Temozolomide Radiotherapy	18 Years -	Novartis

Spots Global Cancer Trial Database for rlt

Every month we try and update this database with for rlt cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for rlt

Every month we try and update this database with for rlt cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for rlt cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.