lutetium zadavotide guraxetan (PNT2002) / Lantheus, Eli Lilly - LARVOL DELTA

STARLiT: STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=45 | Recruiting | Sponsor: Angela Y. Jia, MD PhD | Trial completion date: Sep 2026 ➔ Mar 2027 | Trial primary completion date: Sep 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study. (PubMed, J Clin Oncol) - P2 | "Compared with SBRT alone, the addition of 177Lu-PNT2002 to SBRT significantly improved PFS in patients with orHSPC without an attendant increase in toxicity."

Journal • P2 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Neoadjuvant 177Lutetium-PSMA-617 Radioligand Therapy for High-Risk Localized Prostate Cancer: Rationale, Early Clinical Evidence, and Future Directions. (PubMed, Cancers (Basel)) - "Radioligand therapy with 177Lutetium-PSMA-617 (177Lu-PSMA-617) has emerged as a promising method to eliminate occult micrometastases while enhancing immune-mediated clearance of the primary tumor. Ultimately, large-scale randomized trials are essential to determine whether this investigational approach impacts key clinical outcomes-namely, metastasis-free and overall survival. While the strategy is theoretically sound, its capacity to enhance cure rates for high-risk localized PCa remains unverified."

Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

In LUNAR, also presented at ESMO 2025, patients with 1–5 PSMA PET–positive lesions were randomized 1:1 to receive either stereotactic body radiotherapy alone or two cycles of 177Lu-PNT2002 (6.8 GBq every 8 weeks) followed by stereotactic body radiotherapy. (Urology Times) - "After a median follow-up of 22 months (IQR 19–26), the LUNAR trial met its primary endpoint of progression free survival. The addition of radioligand therapy significantly prolonged median stereotactic body radiotherapy to 17.6 months (95% CI 15 to not reached) compared to 7.4 months (95% CI 6.0–13.5) with stereotactic body radiotherapy alone (HR 0.37, 95% CI 0.22–0.61, p<0.0001)."

P2 data • Prostate Cancer

Prospective randomized phase II trial of 177Lutetium-PSMA therapy neoadjuvant to stereotactic ablative radiotherapy for recurrent oligo-metastatic hormone-sensitive prostate cancer (LUNAR NCT05496959) (ESMO 2025) - P2 | "The only grade 3 adverse events were lymphopenia: 2 patients [4.8%] in the SBRT group and 3 patients [6.7%] in the 177 Lu+SBRT group. Conclusions In this randomized trial, administering 2 cycles of 177Lu-PSMA prior to SBRT improved PFS in men with omHSPC, without increasing toxicity."

Clinical • Late-breaking abstract • Metastases • P2 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer; Primary Endpoint Analysis of the Phase II LUNAR Randomized Trial (ASTRO 2025) - "Materials/ We randomized patients with recurrent omHSPC, characterized by 1-5 lesions outside the prostate or prostate bed on PSMA PET/CT in a 1:1 fashion to receive either SBRT to all metastatic lesions vs. 2 cycles of neoadjuvant 177Lu-PSMA PNT2002 (6.8 GBq/cycles) 6-8 weeks apart followed by SBRT to all metastatic lesions... The addition of 177Lu-PSMA to SBRT more than doubled PFS in this cohort of men with omHSPC, meeting the primary endpoint of the trial, without significantly increasing toxicity."

Clinical • IO biomarker • P2 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • TGFB1

ROADSTER: Radioligand fOr locAl raDiorecurrent proStaTe cancER (clinicaltrials.gov) - P1/2 | N=3 | Completed | Sponsor: Glenn Bauman | Active, not recruiting ➔ Completed | Phase classification: P2 ➔ P1/2 | N=12 ➔ 3

Enrollment change • Phase classification • Trial completion • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

PSMA Therapy and Immunotherapy in Kidney Cancer (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=37 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=48 | Suspended | Sponsor: Weill Medical College of Cornell University | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs

177Lu-PSMA (177Lu-PNT2002) in PSMA-Positive Adenoid Cystic Carcinoma (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Adenoid Cystic Carcinoma • Oncology

Mature phase 1 follow up of alpha emitter 225Ac-J591 with 177Lu-PSMA-I&T in advanced prostate cancer. (ASCO-GU 2025) - P1/2 | "Here, we present mature follow up of a phase 1 dose-escalation trial of 225Ac-J591 plus 177Lu-PSMA-I&T (aka PNT2002)...Previous therapies: 11 (61%) with >1 ARPI, 12 (67%) chemo, 5 (28%) sip-T, 3 (17%) radium-223... The combination of PSMA-targeted alpha (via antibody) plus beta (via small molecule) was feasible. High grade AEs were rare and no new safety signals emerged with longer term follow up. Nearly all patients had PSA decline, and 5 had durable disease control off therapy."

Metastases • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Initial clinical experience with [177Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial. (PubMed, Front Oncol) - P3 | "[177Lu]Lu-PNT2002, administered at 6.8 GBq/cycle for 4 cycles, demonstrated a favorable dosimetry and safety profile, as well as promising preliminary efficacy. https://clinicaltrials.gov/, identifier NCT04647526."

Journal • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hematological Disorders • Oncology • Prostate Cancer • Solid Tumor • Xerostomia

177Lu-PSMA (177Lu-PNT2002) in PSMA-Positive Adenoid Cystic Carcinoma (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2035 ➔ Feb 2035 | Initiation date: Dec 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2030 ➔ Mar 2030

Trial completion date • Trial initiation date • Trial primary completion date • Adenoid Cystic Carcinoma • Oncology

PSMA Therapy and Immunotherapy in Kidney Cancer (clinicaltrials.gov) - P1/2 | N=37 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2031 ➔ Jan 2032 | Initiation date: Nov 2024 ➔ May 2025 | Trial primary completion date: Jul 2030 ➔ Jan 2031

Metastases • Trial completion date • Trial initiation date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Quantitative 68Ga-PSMA-11 PET and Outcomes in Metastatic Castration-resistant Prostate Cancer fol… (YouTube) - "...speaks...Dr. Andrew Armstrong...about how 68Ga-PSMA-11 PET can predict response of metastatic prostate cancer following 177Lu-PSMA-617 therapy. The VISION Trial."

Video

177-Lutetium-PSMA Before Stereotactic Body Radiotherapy for the Treatment of Oligorecurrent Prostate Cancer, The LUNAR Study (clinicaltrials.gov) - P2 | N=93 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2033 | Trial primary completion date: Sep 2024 ➔ Sep 2032

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

177Lu-PSMA (177Lu-PNT2002) in PSMA-Positive Adenoid Cystic Carcinoma (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Sep 2024 ➔ Dec 2024

Trial initiation date • Adenoid Cystic Carcinoma • Oncology

A Pilot Study of Immunological Response to PSMA-Directed Radioligand Therapy for the Treatment of Oligometastatic Prostate Cancer (ASTRO 2024) - "Patients are randomized 1:1 to receive either MDT with SBRT to all sites of disease (control arm) or two cycles of neoadjuvant 177Lu-PNT2002 (6.8 GBq) followed by SBRT to all sites of disease (experimental arm)... In this small pilot study representing the first evaluation of the impact of PSMA-directed RLT on TCRB receptors in oligometastatic prostate cancer, RLT did not appear to result in significant stimulation of the T-cell repertoire of the peripheral immune system beyond SBRT alone, nor was antigen-specific clonal selection evident at early follow-up, though statistical power was likely insufficient. Additional testing to better elucidate potential immunologic effects of RLT on tumor control at additional timepoints is warranted."

Clinical • Metastases • CNS Disorders • Genito-urinary Cancer • Oncology • Prostate Cancer • Psychiatry • Solid Tumor • TRB

Efficacy of 177Lu-PNT2002 in PSMA-positive mCRPC following progression on an androgen-receptor pathway inhibitor (ARPI) (SPLASH) (ESMO 2024) - P3 | "177Lu-PNT2002 was well tolerated and improved rPFS, ORR, PSA50 and HRQoL in patients with PSMA-positive mCRPC in the pre-chemotherapy setting compared to alternative ARPI."

Clinical • Late-breaking abstract • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

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 (GlobeNewswire) - P3 | N=415 | SPLASH (NCT04647526) | Sponsor: POINT Biopharma | "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)....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)."

P3 data: top line • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

First results from the SPLASH ph3 trial Lutetium 177-PNT2002 vs alternate ARPI in mCRPC #ProstateCancer in @myESMO #ESMO24 👉Improved PFS (HR 0.71 , 9.5 vs. 6 months), PSA response, interim OS HR:1.11 vs ARPI👇 @PCF_Science @urotoday @OncoAlert @sartor_oliver

PSMA Therapy and Immunotherapy in Kidney Cancer (clinicaltrials.gov) - P1/2 | N=37 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Jul 2024 ➔ Nov 2024

Metastases • Trial initiation date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Lantheus to Present Additional Clinical Data from Phase 3 Pivotal SPLASH Trial in PSMA-Positive Metastatic Castration-Resistant Prostate Cancer During ESMO Congress 2024 (Lantheus Press Release) - "Lantheus Holdings, Inc...today announced that Oliver Sartor , MD, Director of Radiopharmaceutical Trials and Professor of Medical Oncology at the Mayo Clinic in Rochester, Minnesota, will deliver an oral presentation, including additional clinical data from PNT2002’s initial December 2023 readout, during the European Society of Medical Oncology (ESMO) Annual Meeting in Barcelona on Sunday, September 15, 2024."

P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Prostate Cancer • Solid Tumor

Efficacy and safety of interventions for metastatic castration resistant prostate cancer (mCRPC) patients progressing on androgen receptor-axis-targeted (ARAT) therapy: a systematic literature review. (PubMed, Curr Med Res Opin) - "A total of 16 trials evaluated ARAT based therapies, 7 trials evaluated taxane-based treatments, 10 trials evaluated PARP inhibitors, 8 trials evaluated immunotherapies, and 8 trials evaluated other therapies (i.e. cabozantinib, mitoxantrone, radium-223, 177[Lu-177]-PNT2002, 177Lu-PSMA-617, samotolisib)...Conversely, agents such as taxane-based chemotherapy (e.g. cabazitaxel) and radionuclide therapy provide the most value in this patient population. Further research is needed to explore new therapies in this disease area and to optimize existing treatment strategies with more effective combination therapies."

Journal • Metastases • Review • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

PNT2002: Overall survival data from P3 SPLASH trial (NCT04647526) for mCRPC in Q3 2024 (Lantheus Holdings) - Investor Presentation

P3 data • Metastatic Castration-Resistant Prostate Cancer • Oncology • Solid Tumor