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

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

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 2024 ➔ Dec 2025

Metastases • Trial primary completion date • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate 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: Apr 2024 ➔ Jul 2024

Trial initiation date • Adenoid Cystic Carcinoma • Oncology

MODULE 5: Other Novel Therapies for Patients with Metastatic Prostate Cancer (AUA 2024) - "This activity is CME-accredited by Research To Practice and supported by educational grants from Astellas and Pfizer Inc, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, and Merck. • Available data with, patient selection for and ongoing assessment of radium-223 in prostate cancer • Published Phase III data sets (eg, from the VISION and PSMAfore trials) with lutetium Lu 177 vipivotidetetraxetan for patients with PSMA-positive mCRPC; appropriate sequencing of lutetium Lu 177 vipivotide tetraxetan • Ongoing Phase III PSMAddition trial evaluating lutetium Lu 177 vipivotide tetraxetan in combination with AR-directed therapy and ADT for patients with mHSPC • Emerging positive findings from the Phase III SPLASH trial evaluating the investigational PSMA-targeted radiopharmaceutical 177Lu-PNT2002 for patients with mCRPC who have experienced disease progression on an AR pathway inhibitor and..."

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

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 | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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

Metastases • New P1/2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Hoag First in World to Enroll Prostate Cancer Patients in Molecular Imaging & Therapy Clinical Trials (PRNewswire) - "Hoag is the first site in the world to enroll patients in two clinical trials for prostate cancer staging and treatment....The first trial, MIRROR, will test the use of the imaging agent Pylarify with a whole-body PET/CT scan in men with favorable intermediate prostate cancer, including Gleason Score 3+4 tumors....The second trial provides men with metastatic prostate cancer access to prostate-specific membrane antigen (PSMA)-targeted therapy prior to chemotherapy....Hoag is the first site in the world to open both trials and the first site worldwide to enroll patients on these trials."

Trial status • 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

New P2 trial • Adenoid Cystic Carcinoma • Oncology

Lantheus and POINT Biopharma Announce Positive Topline Results from Pivotal SPLASH Trial in Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - P3 | N=415 | SPLASH (NCT04647526) | Sponsor: POINT Biopharma | "Lantheus Holdings, Inc...and POINT Biopharma Global Inc...announced statistically significant topline results from the pivotal phase 3 SPLASH study evaluating the efficacy and safety of ¹⁷⁷Lu-PNT2002...in patients with metastatic castration-resistant prostate cancer (mCRPC)...The 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 companies expect additional, follow-up data in 2024 prior to the potential submission of a New Drug Application (NDA)....Full SPLASH trial results will be presented at a future medical congress."

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

POINT Biopharma Reports Third Quarter 2023 Financial Results and Provides Business Highlights (GlobeNewswire) - "Enrollment in PNT2002's phase 3 SPLASH trial (NCT04647526) is complete and topline data is expected in the fourth quarter of 2023....Presentation of data from the FRONTIER study is anticipated in the first half of 2024, and based on initial promising data we expect to advance at least one 2nd-generation D-ala-boroPro-based lead into the clinic next year....For the phase 1 portion of ACCEL, the first-in-human phase 1/2 clinical trial for PNT2001's actinium-225 program, we expect the first patient dosed in this trial to be in the first quarter of 2024. The trial was designed to enable the parallel exploration of PNT2001 in two populations: patients with later-stage mCRPC and patients with earlier-stage BCR or PSMA-positive oligorecurrent disease."

New P1 trial • New trial • P1 data • P3 data: top line • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor