Brief Summary
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.
Brief Title
Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC
Detailed Description
This is a phase III, open label, multicenter randomized study. The study aims at evaluating the superiority of 225Ac-PSMA-617 combined with androgen receptor pathway inhibitor (ARPI) over a change of ARPI or chemotherapy or \[177Lu\]Lu-PSMA-617 (AAA617) in prolonging progression free survival (rPFS).
Screening period: At screening, the participants will be assessed for eligibility and will undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized.
Participants randomized to the investigational arms will receive up to 6 doses of AAA817 10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral abiraterone) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria.
Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or \[177Lu\]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion following local guidelines as per standard of care and product labels and adhere to the protocol end of treatment criteria.
Supportive care will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT).
Safety will be assessed routinely during the study. Crossover is not allowed among study arms.
The study will be conducted in the USA among other countries globally.
Screening period: At screening, the participants will be assessed for eligibility and will undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized.
Participants randomized to the investigational arms will receive up to 6 doses of AAA817 10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral abiraterone) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria.
Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or \[177Lu\]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion following local guidelines as per standard of care and product labels and adhere to the protocol end of treatment criteria.
Supportive care will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT).
Safety will be assessed routinely during the study. Crossover is not allowed among study arms.
The study will be conducted in the USA among other countries globally.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-888-669-6682
Central Contact Email
novartis.email@novartis.com
Central Contact Role
Contact
Central Contact Phone
+41613241111
Completion Date
Completion Date Type
Estimated
Conditions
Prostate Cancer
Eligibility Criteria
Key Inclusion Criteria:
* Signed informed consent must be obtained prior to participation in the study.
* Participants must be adults ≥ 18 years of age.
* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
* Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
* 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).
* Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.
Key Exclusion Criteria:
* Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, \[177Lu\]Lu-PSMA, \[177Lu\]-DOTA, or Radium- 223.)
* Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
* Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC). Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization.
Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.
Other protocol-defined inclusion/exclusion criteria may apply.
* Signed informed consent must be obtained prior to participation in the study.
* Participants must be adults ≥ 18 years of age.
* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
* Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
* 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).
* Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.
Key Exclusion Criteria:
* Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, \[177Lu\]Lu-PSMA, \[177Lu\]-DOTA, or Radium- 223.)
* Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
* Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC). Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization.
Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.
Other protocol-defined inclusion/exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Signed informed consent must be obtained prior to participation in the study.
* Participants must be adults ≥ 18 years of age.
* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
* Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
* 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).
* Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.
inclusion/
* Signed informed consent must be obtained prior to participation in the study.
* Participants must be adults ≥ 18 years of age.
* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
* Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
* 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).
* Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.
inclusion/
Gender
Male
Gender Based
false
Keywords
Positive Metastatic Castration Resistant Prostate Cancer
PSMA
PSMA-positive
AAA817
[225AC] AC-PSMA-617
Radioligand Therapy
RLT
Androgen receptor pathway inhibitor
ARPI
Taxane
Metastatic castration resistant prostate cancer
mCRPC
AcTFirst
[177Lu]Lu- PSMA-617
AAA617
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
18 Years
NCT Id
NCT06855277
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CAAA817B12301
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer
Primary Outcomes
Outcome Description
Time to radiographic disease progression or death due to any cause.
Outcome Measure
Radiographic Progression Free Survival (rPFS)
Outcome Time Frame
From the date of randomization to the date of the first documented radiographic disease progression using conventional imaging, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Secondary Ids
Secondary Id
2024-512340-32
Secondary Outcomes
Outcome Description
Time to death due to any cause.
Outcome Time Frame
From the date of randomization to the date of death due to any cause, assessed up to approximately 40 months.
Outcome Measure
Overall Survival (OS) (Key Secondary Endpoint)
Outcome Description
Time to radiographic disease progression, using by blinded independent central review (BICR) using conventional imaging and Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 criteria or death due to any cause.
Outcome Time Frame
From date of randomization to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Radiographic Progression Free Survival by by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 (Key Secondary)
Outcome Description
Time to death due to any cause.
Outcome Time Frame
From the date of randomization to the date of death due to any cause.
Outcome Measure
Overall Survival in participants with PSMA-positive mCRPC treated with another ARPI. (Key Secondary)
Outcome Description
rPFS time to the date of first documented radiographic disease progression or death due to any cause, whichever occurs first.
Outcome Time Frame
From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
rPFS in participants treated with AAA817
Outcome Description
Time to first documented progression or death due to any cause.
Outcome Time Frame
From date of randomization to the first documented progression by investigator's assessment or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
Time to first documented progression on next line of antineoplastic therapy or death from any cause.
Outcome Time Frame
From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to approximately 40.0 months.
Outcome Measure
Progression Free Survival (PFS2)
Outcome Description
The proportion of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in soft tissue.
Outcome Time Frame
From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Overall Response Rate (ORR)
Outcome Description
The proportion of participants with BOR of confirmed CR, PR, stable disease (SD) or non-CR/non-progressive disease (PD) in soft tissue.
Outcome Time Frame
From the date of randomization to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Disease Control Rate (DCR)
Outcome Description
Time between the date of first documented response and the date of first documented radiographic progression or death due to any cause.
Outcome Time Frame
From the date of first documented response (CR or PR) for confirmed responders and the date of first documented radiographic progression in soft tissue or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Duration of Response (DoR)
Outcome Description
Time to radiographic soft tissue progression.
Outcome Time Frame
From the date of randomization to the date of radiographic soft tissue progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Time to first radiographic soft tissue progression (TTSTP)
Outcome Description
Time to date of first new symptomatic skeletal event of death due to any cause.
Outcome Time Frame
From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Time to first symptomatic skeletal event (TTSSE)
Outcome Description
The percentage of participants who achieved ≥ 50% and ≥ 90% decrease from baseline, respectively.
Outcome Time Frame
From the date of randomization to the date of safety follow up, assessed up to approximately 40.0 months.
Outcome Measure
Prostate specific antigen response (PSA50 and PSA90)
Outcome Description
Time-concentration profiles and PK parameters of AAA817 (e.g. AUC, Cmax).
Outcome Time Frame
From Cycle 1 Day 1 up to approximately cycle 5 days 11 (each cycle is 8 weeks).
Outcome Measure
Time-concentration profiles and PK parameters of AAA817
Outcome Description
Change from baseline on FACT-P Prostate Cancer Subscale (PCS). FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment.
Outcome Time Frame
From randomization to the first occurrence of worsening on the score or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Change from baseline on FACT-P Prostate Cancer Subscale (PCS)
Outcome Description
Time to worsening on the Worst Pain is defined as the time from randomization to the first occurrence of worsening on the Worst Pain item (BPI-SF) or death due to any cause, whichever occurs first.
Outcome Time Frame
From randomization to the first occurrence of worsening from baseline, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Outcome Measure
Time to worsening on the Worst Pain
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Prostate Cancer --- PROSTATIC NEOPLASMS
Genitourinary (GU) & Urologic Cancers --- GENITAL NEOPLASMS, MALE
Genitourinary (GU) & Urologic Cancers --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
MeSH Terms
PROSTATIC NEOPLASMS
GENITAL NEOPLASMS, MALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
GENITAL DISEASES, MALE
GENITAL DISEASES
UROGENITAL DISEASES
PROSTATIC DISEASES
MALE UROGENITAL DISEASES
(225)AC-PSMA-617
ENZALUTAMIDE
ABIRATERONE
STANDARD OF CARE
QUALITY INDICATORS, HEALTH CARE
QUALITY OF HEALTH CARE
HEALTH SERVICES ADMINISTRATION
HEALTH CARE QUALITY, ACCESS, AND EVALUATION