SPLASH
In SPLASH, a second PSMA radioligand improved progression-free survival but not, so far, survival.
Overview
SPLASH, trial NCT04647526 sponsored by Lantheus through POINT Biopharma and reported in 2024, tested a second PSMA radioligand, 177Lu-PNT2002, also known as 177Lu-PSMA-I&T, against a switch of androgen receptor pathway inhibitor in PSMA-positive, taxane-naive metastatic castration-resistant prostate cancer. It randomised 412 men and met its primary radiographic progression-free survival endpoint, but the interim overall survival analysis was numerically unfavourable, with 46 percent of events and 84 percent crossover, and Lantheus deprioritised a US filing pending mature data. Nuclide links it to prostate cancer and to the 177Lu-PSMA-I&T drug record; its effect was smaller than PSMAfore's with a different ligand and dosing, while ECLIPSE with the same ligand met its progression endpoint. Whether crossover masked a real benefit or the drug simply adds little is the open question.
- Median 9.5 vs 6 months with 177Lu-PNT2002 (PSMA-I&T) compared with ARPI switch; about 3.5 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 29 percent lower chance of the event at any given time (hazard ratio 0.71, likely range 0.55 to 0.92).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- The treated group had about 11 percent higher chance of the event at any given time (hazard ratio 1.11).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- Numerically unfavourable at interim with crossover
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- Numerically unfavourable at interim with crossover.
- These results apply to the people the trial enrolled: PSMA-positive mCRPC after one ARPI, taxane-naive: 177Lu-PNT2002 vs ARPI switch. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (PSMA); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
455 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Radiographic progression-free survivalprimary | 177Lu-PNT2002 (PSMA-I&T) | 276 | 9.5 months | 0.71 (0.55 to 0.92) | 0.0088 | link |
| ARPI switch | 136 | 6 months | ||||
| Overall survival (interim) | 177Lu-PNT2002 | - | Numerically unfavourable at interim with crossover | 1.11 | - | link |
| ARPI switch | - | - |
Similar pages
not linked directly; found by shared links- TrialECLIPSE
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Shares 177Lu-PSMA-I&T, Metastatic castration-resistant prostate cancer, Lutetium-177.