SPLASH: Study Evaluating Metastatic Castrate Resistant Prostate Cancer Treatment Using 177Lu- PNT2002 PSMA Therapy After Second-line Hormonal Treatment

Phase 3

Recruiting

Conditions: prostate cancer
10027655

Registration Number: NL-OMON54469

Lead Sponsor: POINT BioPharma,

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 30

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:
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: defined as appearance of two or more new
lesions 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 (<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 g/dL.
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 who are pregnant or of childbearing
potential a condom is required along with a highly effective contraceptive
method during the study and for 6 months after last study drug administration.
Such methods deemed highly effective include
a) combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation
b) progestogen-only hormonal contraception associated with inhibition of
ovulation
c) intrauterine device (IUD), d) intrauterine hormone-releasing system (IUS)
e) bilateral tubal occlusion
f) vasectomy
g) sexual abstinence.
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

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)
are excluded if they are not 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. Dose escalation or initiation of opioids for cancer-related pain <=30 days
prior to consent up to and including randomization.
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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Efficacy Objective:<br /><br>To determine the efficacy of 177Lu-PNT2002 versus abiraterone or enzalutamide<br /><br>in delaying radiographic progression in patients with mCRPC who have progressed<br /><br>on ARAT.<br /><br>Primary Endpoint:<br /><br>Radiological progression-free survival (rPFS) assessed by Blinded Independent<br /><br>Central Review (BICR) using Response Evaluation Criteria in Solid Tumors<br /><br>(RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone)<br /><br>criteria.</p><br>

Secondary Outcome Measures