Metastatic Castrate Resistant Prostate Cancer (mCRPC) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: 177Lu-PNT2002
Product Code: 177Lu-PNT2002
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: 14265-75-9
Current Sponsor code: 177LU-PNT2002
Other descriptiv
Sponsors
Point BioPharma Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if all of the following criteria apply: 1. Male aged 18 years or older. 2. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate. 3. Ineligible or averse to chemotherapeutic treatment options. 4. Patients must have progressive mCRPC at the time of consent based on at least 1 of the following criteria: a. Serum/plasma PSA progression defined as increase in PSA greater than 25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart. b. Soft-tissue progression defined as an increase =20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or a new lesion. c. Progression of bone disease: evaluable disease or one new bone lesion by bone scan 5. Progression on previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or apalutamide) in either the CSPC or CRPC setting. 6. PSMA-PET scan (i.e., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by the sponsor's central reader. 7. Castrate circulating testosterone levels (=65 years) yes F.1.3.1 Number of subjects for this age range 273
Exclusion criteria
Exclusion criteria: Patients are excluded from the study if any of the following criteria apply: 1. If noted in pathology report, prostate cancer with known significant (>10% present in cells) sarcomatoid or spindle cell or neuroendocrine components. Any small cell component in the cancer should result in exclusion. 2. Prior treatment for prostate cancer =28 days prior to randomization, with the exclusion of first line local external beam, ARAT, luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy, or non-radioactive bone-targeted agents. 3. Any prior cytotoxic chemotherapy for CRPC (e.g., cabazitaxel or docetaxel); chemotherapy for hormone-sensitive prostate cancer (HSPC) is allowed if the last dose was administered >1 year prior to consent. 4. Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium-89). 5. Prior immuno-therapy, except for sipuleucel-T. 6. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095. 7. Prior poly ADP ribose polymerase (PARP) inhibitor for prostate cancer. 8. Patients who progressed on 2 or more lines of ARATs. 9. Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) must be on stable doses for at least 4 weeks prior to randomization. 10. Administration of an investigational agent =60 days or 5 half-lives, whichever is shorter, prior to randomization. 11. Major surgery =30 days prior to randomization. 12. Estimated life expectancy 1 cm on abdominal imaging. 14. A superscan on bone scan defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity71. 15. Use of opioids for cancer-related pain =30 days prior to consent. 16. Known presence of central nervous system metastases. 17. Contraindications to the use of planned ARAT therapy. 18. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer. 19. Concurrent illness that may jeopardize the patient’s ability to undergo study procedures. 20. Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule. Patients that travel need to be capable of repeated visits even if they are on the control arm. 21. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. 22. Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, unstable ischemia, uncontrolled symptomatic arrhythmia, history of congenital prolonged QT syndrome, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of 177Lu- PNT2002 versus abiraterone or enzalutamide in delaying radiographic progression in patients with mCRPC who have progressed on ARAT.;Secondary Objective: Efficacy: To assess the radiographic response to 177Lu-PNT2002 versus abiraterone or enzalutamide. To determine the effect of 177 Lu-PNT2002 versus abiraterone or enzalutamide on overall survival in patients who have progressed on ARAT. To determine the effect of 177Lu-PNT2002 versus abiraterone or enzalutamide on PSA kinetics in patients who have progressed on ARAT. Safety: To evaluate the safety and tolerability of 177Lu-PNT2002 versus abiraterone or enzalutamide. Exploratory: To evaluate the efficacy of tracer uptake in PSMA-PET for patient selection with 177Lu-PNT2002 therapy. To determine the effect of 177Lu-PNT2002 versus abiraterone or enzalutamide on cancer related pain in patients who have progressed on ARAT. To determine the impact of 177Lu-PNT2002 versus abiraterone or enzalutamide on health related quality of life (HRQoL). To further assess the efficacy of 177Lu-PNT2002 versus abiraterone or enzalutamide.;Primary end point(s): Radiological progression-free survival (rPFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone) criteria.;Timepoint(s) of evaluation of this end point: Screening and every 8 weeks from 1st dose until progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective response rate (ORR): proportion of patients with partial or complete response (PR or CR, respectively) by BICR based on RECIST 1.1 criteria (soft tissue) and PCWG3 criteria (bone). • Duration of response: time from the first date of CR or PR by BICR to the first occurrence of radiographic progression (PD) by BICR based on PCWG3 modified RECIST 1.1, or death in the absence of progression. • Overall survival (OS): time from randomization to date of death from any cause. • PSA response rate according to PCWG3 criteria (first occurrence of a 50% or more decline in PSA from baseline, confirmed by a second measurement at least 3 weeks later). • Biochemical progression-free survival (bPFS): time from randomization to the date of the first PSA increase from baseline =25% and =2 ng/mL above nadir confirmed by a second PSA measurement defining progression =3 weeks later per PCWG3. • Frequency and severity of AEs, graded and categorized using CTCAE v. 5.0. • Changes from baseline in physical exam findings, vital signs, clinical laboratory values, and ECG values. • Number of patients discontinuing study drug due to AEs. • PSMA-PET and FDG-PET concordance/discordance with treatment response. • Correlation of tracer uptake defined by SUVmax and SUVmean at initial screening with treatment response. • Correlation of tracer uptake defined by SUVmax and mean SUVmean at initial screening with treatment failure. • Within measurable disease sites, correlation of SUV with individual lesion response. • Time from randomization to opioid use for cancer-related pain. • Use of opioids quantified by Analgesic Quantification Algorithm (AQA) score. • Time from randomization to first symptomatic skeletal-related event. • Pain palliation: decrease of =2 points in Brief Pain Inventory – Short Form (BPI-SF) item 3 at 12 weeks without a =1 point increase in AQA score. • Absolute and change from baseline scores of pain severity and interference, assessed by BPI-SF. | — |
Countries
Canada, France, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactEVP, Clinical Development
Point BioPharma Inc.
Outcome results
None listed