Clinical Trials /

Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment

NCT04647526

Description:

The purpose of this study is to evaluate the efficacy and safety of [Lu-177]-PNT2002 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with androgen receptor axis-targeted therapy (ARAT).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment
  • Official Title: A Phase 3, Open-Label, Randomized Study Evaluating Metastatic Castrate Resistant Prostate Cancer Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment (SPLASH)

Clinical Trial IDs

  • ORG STUDY ID: PBP-301
  • NCT ID: NCT04647526

Conditions

  • Metastatic Castration-Resistant Prostate Cancer

Interventions

DrugSynonymsArms
[Lu-177]-PNT2002[Lu-177]-PSMA-I&T[Lu-177]-PNT2002 (Arm A)
AbirateroneControl Arm (Arm B)
EnzalutamideControl Arm (Arm B)

Purpose

The purpose of this study is to evaluate the efficacy and safety of [Lu-177]-PNT2002 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with androgen receptor axis-targeted therapy (ARAT).

Detailed Description

      The primary objective of the study is to determine the efficacy of [Lu-177]-PNT2002
      ([Lu-177]-PSMA-I&T) versus abiraterone or enzalutamide in delaying radiographic progression
      in patients with mCRPC.

      The study consists of 3 phases: Dosimetry, Randomized Treatment, and Long term Follow up.

      The study will commence with a 25-patient safety and dosimetry lead-in (Part 1) and proceed
      to a randomization treatment phase in approximately 390 patients (Part 2). Patients in Part 2
      will be randomized in a 2:1 ratio to receive either [Lu-177]-PNT2002 (Arm A), or enzalutamide
      or abiraterone (Arm B). Patients in Arm B who experience radiographic progression per central
      review and meet protocol defined eligibility, may crossover to receive [Lu-177]-PNT2002. All
      patients will be followed in long-term follow-up for at least 5 years from the first
      therapeutic dose, death, or loss to follow up (Part 3).

      Only patients that meet PSMA PET avidity criteria per central review will be eligible for
      this study.
    

Trial Arms

NameTypeDescriptionInterventions
[Lu-177]-PNT2002 (Arm A)Experimental[Lu-177]-PNT2002 (6.8 GBq (±10%) every 8 weeks for 4 cycles)
  • [Lu-177]-PNT2002
Control Arm (Arm B)Active ComparatorAbiraterone (1000 mg orally qd with: 5 mg bid prednisone or 0.5 mg qd dexamethasone) or enzalutamide (160 mg orally qd).
  • Abiraterone
  • Enzalutamide

Eligibility Criteria

        Inclusion Criteria:

          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:

               1. 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.

               2. 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.

               3. Progression of bone disease: evaluable disease or one new bone lesion by bone
                  scan

          5. 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 (<1.7 nmol/L or <50 ng/dL).

          8. Adequate organ function, independent of transfusion:

             a. Bone marrow reserve: i. White blood cell (WBC) count ≥2.5 × 109/L OR absolute
             neutrophil count (ANC) ≥1.5 × 109/L.

             ii. Platelets ≥100 × 109/L. iii. Hemoglobin ≥8 mmol/L. b. Liver function: i. Total
             bilirubin ≤1.5 × institutional upper limit of normal (ULN). For patients with known
             Gilbert's syndrome, ≤3 × ULN is permitted.

             ii. ALT or AST ≤3.0× ULN. c. Renal function: i. Serum/plasma creatinine ≤1.5 × ULN or
             creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula.

             d. Albumin ≥30 g/L.

          9. Human immunodeficiency virus-infected patients who are healthy and have a low risk of
             acquired immunodeficiency syndrome-related outcomes are included in this trial.

         10. For patients who have partners of childbearing potential: Partner and/or patient must
             use a method of birth control with adequate barrier protection, deemed acceptable by
             the principal investigator during the study and for 6 months after last study drug
             administration.

         11. Willing to initiate ARAT therapy (either enzalutamide or abiraterone), pre-specified
             by investigator, if randomized to Treatment Arm B.

         12. ECOG performance status 0 to 1.

         13. Willing and able to comply with all study requirements and treatments (including 177Lu
             PNT2002) as well as the timing and nature of required assessments.

         14. Signed informed consent.

        Exclusion Criteria:

        Patients are excluded from the study if any of the following criteria apply:

          1. Prostate cancer with known significant (>10%) 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) 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 have had 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 <6 months as assessed by the principal investigator.

         13. Presence of liver metastases >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 (see 12.1 Appendix 1), 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Radiographic Progression Free Survival (rPFS)
Time Frame:32 weeks
Safety Issue:
Description:Time in months from the date of randomization to radiological progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) or confirmed progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3) (bone), or death from any cause, as assessed by blinded independent central review (BICR).

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:32 weeks
Safety Issue:
Description: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).
Measure:Duration of response
Time Frame:32 weeks
Safety Issue:
Description: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.
Measure:Overall Survival
Time Frame:5 years
Safety Issue:
Description:Time from the date of randomization until death due to any cause.
Measure:PSA Response
Time Frame:32 weeks
Safety Issue:
Description:Proportion of patients achieving a ≥50% decrease in PSA (PCWG3 criteria) from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.
Measure:Biochemical Progression-Free Survival (bPFS)
Time Frame:32 weeks
Safety Issue:
Description: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, as per PCWG3.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:POINT Biopharma

Trial Keywords

  • PSMA
  • mCRPC
  • Prostate cancer
  • 177Lu-PSMA
  • radioligand therapy
  • PSMA-I&T
  • SPLASH

Last Updated

March 22, 2021