pelgifatamab corixetan (BAY 2315497) / Bayer - LARVOL DELTA

Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=63 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: Bayer | Trial completion date: Nov 2023 ➔ Nov 2024

Combination therapy • Metastases • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] PSMA-Targeted Thorium Conjugate (BAY 2315497) and olaparib combination show synergistic anti-tumor activity in prostate cancer models (AACR 2021) - P1 | "Changes in markers of DNA damage response following treatment will be presented. In summary, combination of PSMA-TTC with olaparib shows synergistic preclinical anti-tumor activity and support further clinical investigation of this combination treatment in prostate cancer patients."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA2 • HRD

PSMA-targeted thorium‑227 conjugate (PSMA-TTC) inhibits tumor growth and abnormal bone changes in the intratibial LNCaP xenograft model of bone-metastatic prostate cancer (AACR 2022) - P1 | "PSMA‑TTC uptake relative to tibia weight was higher in the tumor-bearing tibiae compared with the non-tumor-bearing tibiae, resulting in higher levels of thorium-227 and its daughter isotype radium-223 both 3 days and 3 weeks post injection.In this preclinical study, PSMA-TTC showed robust antitumor efficacy, for the first time, in a model mimicking prostate cancer metastasized to bone as evidenced by a decrease in serum PSA levels, tumor-induced abnormal bone changes, and tumor-bearing tibia weights in the PSMA-TTC-treated mice. Taken together, our data indicate activity of PSMA-TTC in bone-metastatic CRPC. PSMA-TTC as a monotherapy as well as in combination with darolutamide is currently being investigated in patients with mCRPC in a phase 1 clinical trial (NCT03724747)."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: Bayer | Trial primary completion date: Nov 2022 ➔ Aug 2022

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

Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting | N=198 ➔ 63 | Trial completion date: Sep 2024 ➔ Nov 2023 | Trial primary completion date: Sep 2024 ➔ Nov 2022

Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Darolutamide potentiates the antitumor efficacy of a PSMA-targeted thorium-227 conjugate (PSMA-TTC) in a hormone-independent prostate cancer model (AACR 2022) - "These data indicate that darolutamide induces PSMA expression in the hormone independent 22Rv1 model, which may have contributed to the stronger efficacy observed when combined with PSMA-TTC. Altogether these results support the further evaluation of darolutamide combination with PSMA radionuclides."

Clinical • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • CDKN1A • FOLH1 • XRCC2 • XRCC3

BAY-8400: A Novel Potent and Selective DNA-PK Inhibitor which Shows Synergistic Efficacy in Combination with Targeted Alpha Therapies. (PubMed, J Med Chem) - "In in vitro studies, BAY-8400 showed synergistic activity of DNA-PK inhibition with DNA damage-inducing targeted alpha therapy. Combination of PSMA-targeted thorium-227 conjugate BAY 2315497 treatment of human prostate tumor-bearing mice with BAY-8400 oral treatment increased antitumor efficacy, as compared to PSMA-targeted thorium-227 conjugate monotherapy."

Clinical • Combination therapy • Journal • Ataxia • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Prostate Cancer

Darolutamide potentiates the antitumor efficacy of a PSMA-targeted thorium-227 conjugate (PSMA-TTC) by a dual mode-of-action in prostate cancer models. (PubMed, Clin Cancer Res) - "In vivo, the combination treatment showed synergistic antitumor efficacy in the low PSMA-expressing VCaP and in the high PSMA-expressing ST1273 prostate cancer models, and enhanced efficacy in the enzalutamide-resistant KUCaP-1 model. Mode-of-action studies revealed that darolutamide induced PSMA expression, resulting in higher tumor uptake of PSMA-TTC, and consequently, higher antitumor efficacy, and impaired PSMA-TTC-mediated induction of DNA damage repair genes, potentially contributing to increased DNA damage. Conclusions/ These results provide a strong rationale to investigate PSMA-TTC in combination with AR inhibitors in patients with prostate cancer."

Clinical • Journal • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1; N=157; Recruiting; Sponsor: Bayer; Trial completion date: Sep 2023 ➔ Jul 2024; Trial primary completion date: Sep 2023 ➔ Jul 2024

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

Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1; N=157; Recruiting; Sponsor: Bayer; N=119 ➔ 157

Clinical • Enrollment change • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] PSMA-targeted thorium conjugate and darolutamide combination show synergistic anti-tumor activity and reduced expression of DNA damage repair genes in prostate cancer models (AACR-II 2020) - "The combination of PSMA-TTC plus darolutamide resulted in significantly lower final tumor weights compared to all other treatment groups. These data indicate that darolutamide induces PSMA expression and impairs DDR genes expression, which may have contributed to increased DNA damage and stronger efficacy when combined with PSMA-TTC."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CDKN1A • FOLH1

Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1; N=111; Recruiting; Sponsor: Bayer; Trial completion date: Nov 2022 ➔ Sep 2023; Trial primary completion date: Sep 2022 ➔ Sep 2023

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

Preclinical efficacy of a PSMA-targeted thorium-227 conjugate (PSMA-TTC), a targeted alpha therapy for prostate cancer. (PubMed, Clin Cancer Res) - P1; "In vivo, PSMA-TTC showed strong antitumor efficacy with T/C values of 0.01-0.31 after a single injection at 300-500 kBq/kg in subcutaneous cell line and PDX models including models resistant to standard-of-care drugs such as enzalutamide. Specific tumor uptake and efficacy were demonstrated using various PSMA-TTC doses and dosing schedules. Induction of DNA double-strand breaks was identified as a key mode-of-action for PSMA-TTC both in vitro and in vivo The strong preclinical antitumor activity of PSMA-TTC supports its clinical evaluation, and a phase I trial is ongoing in mCRPC patients (NCT03724747)."

Journal • Preclinical • FOLH1