KPG-121 / Kangpu Biopharma - LARVOL DELTA

KPG-121, a novel cereblon modulator, in patients with metastatic castration resistant prostate cancer: Results of a phase I multiple ascending dose study. (ASCO 2024) - P1 | "KPG-121 is a novel lenalidomide analogue that binds to CRL4-Cereblon (CRBN) with stronger interaction with CRBN, enhanced immunomodulatory activity, and greater anti-proliferative/anti-angiogenic properties when compared to lenalidomide. KPG-121 demonstrated synergy when combined with abiraterone, enzalutamide, apalutamide, and darolutamide in vitro and in vivo in preclinical studies... KPG-121 1. 5 mg and 2. 5 mg were generally well tolerated and showed meaningful clinical activity based on the preliminary efficacy data in mCRPC pts."

Clinical • Metastases • P1 data • Anemia • Genito-urinary Cancer • Hematological Disorders • Infectious Disease • Metastatic Castration-Resistant Prostate Cancer • Neutropenia • Novel Coronavirus Disease • Oncology • Prostate Cancer • Solid Tumor • Thrombocytopenia • CRBN • IL17RB

FDA Approved Phase II/III Clinical Study of KPG-121 in Combination with Abiraterone as a First Line Treatment for mCRPC (PRNewswire) - "Kangpu Biopharmaceuticals today announced that the U.S. Food and Drug Administration (FDA) has recently approved a Phase II/III clinical trial of KPG-121 in combination with Abiraterone for a first-line treatment of metastatic castration resistant prostate cancer (mCRPC)."

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

FDA approves phase 2/3 trial of KPG-121 plus abiraterone in mCRPC (Urology Times) - P1 | N=16 | NCT03569280 | Sponsor: Kangpu Biopharmaceuticals, Ltd | "In total, 88 treatment-emergent adverse events (TEAEs) were observed across 12 patients (75%) in the study...AEs reported in 2 or more patients included neutropenia (56.3%), a decrease in white blood cell count (43.8%), a decrease in platelet count (37.5%), anemia (25.0%), thrombocytopenia (18.8%), a decrease in lymphocyte count (12.5%), electrocardiogram QT prolonged (12.5%), and muscle spasm (12.5%)...Preliminary efficacy analyses of KPG-121 showed that of the 8 patients with RECIST evaluable disease, 3 patients (37.5%) achieved a partial response and 3 patients (37.5%) achieved stable disease. The objective response rate and disease control rate in the study were 37.5% and 75.0%, respectively...An analysis of pharmacokinetics also showed dose-proportionality among the cohorts, with the t1/2 value ranging from 2.66 to 2.83."

IND • New P2/3 trial • Castration-Resistant Prostate Cancer • Metastatic Castration-Resistant Prostate Cancer • Prostate Cancer

A case report of metastatic castration resistant prostate cancer patient with AR F877L mutation treated with KPG-121 in combination with enzalutamide (SITC 2023) - P1 | "KPG-121 significantly improves anti-tumor efficacies when combined with androgen-receptor antagonists including enzalutamide, abiraterone acetate, apalutamide, or darolutamide in xenograft models when compared to the androgen-receptor antagonist therapy alone. KPG-121 is more potent in degrading CK1α than lenalidomide in vitro...The patient had a medical history of osteoarthritis and his prior treatments included bicalutamide, leuprorelin, sipuleucel-T, enzalutamide, and intensity-modulated radiotherapy. The patient’s ongoing treatments included denosumab since Aug 2014, degarelix since Jul 2016, and enzalutamide Oct 2019 with baseline PSA level of 1...Conclusions KPG-121 in combination with enzalutamide could potentially overcome enzalutamide resistance in prostate cancer. A trial of larger and longer duration of KPG-121 in combination with enzalutamide is needed to further evaluate the efficacy and safety of KPG-121 in enzalutamide resistant patients."

Clinical • Combination therapy • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CRBN • IKZF1

Evaluation of Safety and Efficacy of KPG-121 Plus Enzalutamide, Abiraterone or Apalutamide in CRPC Patients (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Kangpu Biopharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

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

Evaluation of Safety and Efficacy of KPG-121 Plus Enzalutamide, Abiraterone or Apalutamide in CRPC Patients (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Kangpu Biopharmaceuticals, Ltd. | Recruiting ➔ Active, not recruiting | N=36 ➔ 16 | Trial completion date: Dec 2022 ➔ Apr 2023

Enrollment change • Enrollment closed • Metastases • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Evaluation of Safety and Efficacy of KPG-121 Plus Enzalutamide, Abiraterone or Apalutamide in CRPC Patients (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Kangpu Biopharmaceuticals, Ltd. | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Dec 2021 ➔ Dec 2022

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

Evaluation of Safety and Efficacy of KPG-121 Plus Enzalutamide, Abiraterone or Apalutamide in CRPC Patients (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Kangpu Biopharmaceuticals, Ltd.; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Dec 2021

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

[VIRTUAL] KPG-121, a novel CRBN modulator, potently inhibits growth of metastatic castration resistant prostate cancer as a single agent or in combination with androgen receptor signaling inhibitors both in vitro and in vivo (AACR-II 2020) - "KPG-121 is a novel generation of Lenalidomide analogue. Results from in vivo metastatic castration resistant prostate cancer xenograft models demonstrated that KPG-121 at tested daily dose levels ranging from 1.0 mg/kg to 10 mg/kg in combination with Enzalutamide, Abiraterone Acetate, Apalutamide or Darolutamide significantly improved anti-tumor efficacy compared to the AR signaling inhibitors alone. In addition, KPG-121 showed favorable DMPK profiles and potentially manageable toxicity in pre-clinical IND enabling study."

Combination therapy • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CRBN

Kangpu to Present Two Posters at the 2020 American Association for Cancer Research (AACR) Annual Meeting (PRNewswire) - "KPG-121 significantly improves anti-tumor efficacies when combined with androgen-receptor antagonists including Enzalutamide, Abiraterone Acetate, Apalutamide, or Darolutamide in xenograft models when compared to the androgen-receptor antagonist therapy alone....In preclinical studies, KPG-818 demonstrates outstanding in vitro anti-inflammatory properties and broad spectrum of anti-proliferative activities as well as remarkable in vivo efficacy in animal models of multiple blood cancers."

Preclinical • Genito-urinary Cancer • Hematological Malignancies • Oncology • Prostate Cancer