- Study met its primary endpoint, demonstrating significant improvement in radiographic progression-free survival
- Overall Response Rate was 38.1% vs. 12.0% for the ARPI switch arm, including 9.3% Complete Responses
- Patients demonstrated statistically significant improvement in time to reduction of health-related quality of life (HRQoL) as measured by Functional Assessment of Cancer Therapy—Prostate (FACT-P)
- Interim Overall Survival Crossover Adjusted Hazard Ratio was <1.00 when Assessed Using Two-Stage and Inverse Probability Censoring Weighting Methods
- Overall Survival data continue to mature, an update is expected once data are available for 75% of protocol-specified target OS events
Reno, Nevada (UroToday.com) -- Lantheus Holdings, Inc. (“Lantheus”) (NASDAQ: LNTH), the leading radiopharmaceutical-focused company committed to enabling clinicians to Find, Fight and Follow disease to deliver better patient outcomes, presented additional clinical data from initial topline results of the SPLASH Phase 3 trial evaluating the efficacy of 177Lu-PNT2002, a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), administered at 6.8 GBq every 8 weeks for up to 4 cycles in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on androgen receptor pathway inhibitor (ARPI). Data were presented during the European Society of Medical Oncology (ESMO) Congress 2024, which is taking place in Barcelona, Spain.
“We are encouraged by the initial results from the SPLASH trial, with 177Lu-PNT2002 demonstrating improvement compared to ARPI change in radiographic progression-free survival, positive interim crossover-adjusted overall survival hazard ratios, as well as improved quality of life,” said Oliver Sartor, M.D., Director of Radiopharmaceutical Trials and Professor of Medical Oncology at the Mayo Clinic in Rochester, Minnesota. “These initial data underscore the importance of PSMA-targeted RLTs, including 177Lu-PNT2002, as potential treatment options for patients who have limited choices after progressing on ARPI therapy.”
| Efficacy Endpoint | 177Lu-PNT2002 vs. ARPI | ||
| Radiographic Progression-Free Survival (rPFS) | HR 0.71 (CI: 0.55, 0.92; p=0.0088) | ||
| Median rPFS | 9.5 vs. 6.0 months | ||
| OS HR (46% of protocol-specified target OS events reached). | 1.11 (0.73, 1.69; p=0.6154) | ||
| OS HR crossover adjusted: prespecified RPSFTM* | 1.14 (0.54, 2.53) | ||
| Two-Stage Method: no recensoring** | 0.68 (0.44, 1.04) | ||
| Two-Stage Method: recensoring** | 0.85 (0.53, 1.36) | ||
| Inverse Probability Censoring Weighting (IPCW)** | 0.72 (0.48, 1.12) | ||
| Objective Response Rate (ORR) by BICR*** | 38.1% vs. 12.0% (p=0.0021) | ||
| Median Duration of Response (DOR) | 9.4 vs. 7.3 months | ||
| PSA50 Response**** | 35.7% vs. 14.6% | ||
| Biochemical Progression Free Survival (bPFS) | 7.0 vs. 3.9 months (HR 0.58; CI: 0.44, 0.76; p<0.0001) | ||
| Median time to deterioration by FACT-P | 8.1 vs. 5.3 months (HR 0.59; CI: 0.44, 0.80; p=0.0005) | ||
| Time to Opioid Use for Cancer-Related Pain | HR 0.64 (CI: 0.42, 0.98; p=0.0366) | ||
*Overlapping OS curves suggest potential violation of statistical assumptions in RPSFTM method; **exploratory analyses; ***confirmed and unconfirmed ORR; ****evaluable subjects with baseline PSA value
The pivotal SPLASH trial met its primary endpoint, demonstrating a median radiographic progression-free survival (rPFS) per blinded independent central review of 9.5 months for patients treated with 177Lu-PNT2002, compared to 6.0 months for patients treated with ARPI in the control arm, a statistically significant 29% reduction in the risk of radiographic progression or death (hazard ratio [HR] 0.71; p=0.0088). In the SPLASH study, 177Lu-PNT2002 patients demonstrated significantly improved ORR, PSA50 reduction, time to reduction of HRQoL, and time to opioid use for cancer-related pain in PSMA-positive mCRPC patients who had progressed on an ARPI. At the time of the analysis, 84.6% of patients who experienced progressive disease in the control arm subsequently crossed over to receive 177Lu-PNT2002. The overall survival (OS) results at 46% of protocol-specified target OS events reached had a HR of 1.11, with additional crossover adjusted HRs for rank preserving structural failure time model (RPSFTM): (1.14); Two-Stage: no recensoring (0.68); Two-Stage recensoring (0.85); and Inverse Probability Censoring Weighting (0.72).
177Lu-PNT2002 also demonstrated a favorable safety profile compared to patients treated with ARPI in the control arm. Only 3.0% of patients treated with 177Lu-PNT2002 halted or reduced therapy as a result of treatment-emergent adverse events (TEAEs), compared to 11.5% of patients treated with ARPI, and 17.1% of 177Lu-PNT2002 patients experienced serious TEAEs compared to 23.1% of ARPI patients.
| Adverse Events | 177Lu-PNT2002 | ARPI |
| Treatment-related AEs grade ≥ 3 | 9.7% (26/269) | 11.5% (15/130) |
| Treatment-related serious AEs | 2.2% (6/269) | 3.8% (5/130) |
| Treatment-related AEs leading to death | 0.0% (0/269) | 0.0% (0/130) |
“177Lu-PNT2002 is outperforming the control arm and showing an improved quality of life for patients based on this interim analysis,” said Jeff Humphrey, M.D., Chief Medical Officer at Lantheus. “We are grateful to the patients and investigators who participated in this trial thereby helping to advance this important potential treatment option.”
Source: Lantheus Holdings, Inc. (2024). Lantheus Presents Results from the Primary Analysis of Phase 3 Pivotal SPLASH Trial in PSMA-Positive Metastatic Castration-Resistant Prostate Cancer During ESMO Congress 2024 [Press release]. https://lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-presents-results-primary-analysis-phase-3-pivotal.
Related Content:
ESMO 2024: Efficacy of 177Lu-PNT2002 in PSMA-Positive mCRPC Following Progression on an Androgen-Receptor Pathway Inhibitor (SPLASH)