Jeselhy (pimitespib) / Otsuka - LARVOL DELTA

Strong Hsp90α/β Protein Expression in Advanced Primary CRC Indicates Short Survival and Predicts Response to the Hsp90α/β-Specific Inhibitor Pimitespib. (PubMed, Cells) - "Pimitespib (Pim, TAS-116), a Hsp90α/β-specific inhibitor, was tested in pCRC cell lines and patient-derived cancer spheroids (PDCS) and referenced to the pan-Hsp90 inhibitor ganetespib (Gan, STA-9090) and standard-of-care therapies...Pim efficacy was increased in combination with 5-FU, 5-FU + oxaliplatin, and 5-FU + irinotecan (all p 40% pCRCs. Protein profiling combined with functional drug testing stratifies Hsp90α/β > 40% pCRC patients diagnosed with UICC IIb-IV for effective Pim-based therapy."

Journal • Colorectal Cancer • Oncology • Solid Tumor • BRAF • CDC37 • HER-2 • HSP90AA1

A phase 1 study of PARP inhibitor (niraparib) plus HSP90 inhibitor (pimitespib) in solid tumors: Dose-expansion results from the NiraPim (EPOC2102) study. (ASCO 2025) - P1 | "In cohort A, one patient with hormone receptor-positive breast cancer achieved partial response post-olaparib progression... The dose-expansion part demonstrated a manageable safety profile and potential efficacy at the recommended dose of niraparib plus pimitespib. Clinical benefit was observed in both BRCA-associated cancers resistant to PARP inhibitors and PARP inhibitor-naive non-BRCA associated cancers, supporting further investigation in biomarker-selected populations."

P1 data • Anorexia • Breast Cancer • Fatigue • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leiomyosarcoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Sarcoma • Solid Tumor • Urothelial Cancer • BRCA • CDC37 • CDK12 • HRD

Structural Insights into Selectively Targeting Candida albicans Hsp90. (PubMed, Biochemistry) - "We support these studies with crystal structures of five diverse human Hsp90 ligands in complex with CaHsp90, as well as the structure of this protein with a nonhydrolyzable ATP analog. We demonstrate the structural basis for the selectivity of the human Hsp90 inhibitor TAS116 for CaHsp90, features that may be exploited in the future development of improved CaHsp90 inhibitors."

Journal • CDC37 • HSP90AA1

Pimitespib therapy for a patient with PDGFRA D842V-mutant gastrointestinal stromal tumor. (PubMed, Clin J Gastroenterol) - "Regorafenib was introduced but failed immediately owing to tumor penetration. Although based on a single case, this report demonstrates a significant metabolic response to pimitespib in PDGFRA-mutant GIST. More cases are required to fully elucidate the efficacy of this therapy against such rare tumors."

Journal • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

Structural Optimization of Pyrazole Compounds as Hsp90 Regulators with Enhanced Antitumor Activity. (PubMed, J Med Chem) - "TAS-116 has been approved for the treatment of gastrointestinal stromal tumors...Importantly, compound 39 displayed potent tumor growth inhibition in HCT-116 xenograft mouse models. These collective findings underscore the therapeutic promise of covalent Hsp90-targeted disruption of the Hsp90-Cdc37 complex, offering a novel mechanistic approach to cancer treatment."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • CDC37 • HSP90AA1

Pimitespib (TAS-116), an HSP90 inhibitor, overcomes resistance to androgen receptor pathway inhibitors in prostate cancer by simultaneously targeting several key resistance mechanisms (AACR 2025) - "Antitumor efficacy was evaluated in two castration-resistant prostate cancer (CRPC) xenograft models (LNCaP-Xeno-IL-6 and VCaP). Pimitespib enhanced the efficacy of three ARPIs (enzalutamide, darolutamide, and abiraterone) in the four prostate cancer cell lines. Pimitespib effectively addresses ARPI resistance in mCRPC by rapidly inhibiting AR and GR nuclear translocation and reducing the protein levels of AR, GR, AR-V7, and AKT. In addition, our findings highlight the potential of combining pimitespib with ARPIs for the treatment of mCRPC patients who have progressed on ARPI therapy."

Castration-Resistant Prostate Cancer • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • CDC37 • IL6

The cyclopeptide enniatin a inhibits the chaperone hsp90 and induces mitophagy in breast cancer cells (AACR 2025) - "Except for the Pimitespib (TAS-116), approved for clinical use in Japan in 2022, no Hsp90 inhibitors have yet been approved by the FDA...We also show that targeting Hsp90 by EnnA reduced the level of cox4, a component of the electron transport chain, leading to parkin-mediated mitophagy. Our data indicate that EnnA represents a member of a new class of Hsp90 inhibitors that impair mitochondrial function in cancer cells and is a promising compound to treat breast cancer."

Breast Cancer • Oncology • Solid Tumor • CDC37 • HSP90AA1

Pimitespib, an HSP90 Inhibitor, Enhances the Efficacy of PARP Inhibitors in PARP Inhibitor-Insensitive Breast Cancer Cells. (PubMed, Cancer Sci) - "In human breast cancer xenograft mouse models, pimitespib downregulated RAD51 proteins and augmented the antitumor effects of PARP inhibitors. These findings highlight the potential of pimitespib as a therapeutic agent in combination with PARP inhibitors to treat PARP inhibitor-insensitive cancers."

Journal • Breast Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • BRCA1 • BRCA2 • CDC37 • RAD51

The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art. (PubMed, Eur Respir Rev) - "Experimental drugs such as geldanamycin and its derivatives 17-AAG (17-N-allylamino-17-demethoxygeldanamicin) and 17-DMAG (17-dimethylaminoethylamino-17-demethoxigeldanamycin), along with AUY-922, 1G6-D7, AT-13387, TAS-116 and myricetin, have been found to reduce lung fibrosis in both in vivo and in vitro models, supporting the role of this emerging target. This review aims to illustrate the structure and biological function of HSP 90 in the context of IPF pathobiology, as well as perspective application of this molecule as a biomarker and therapeutic target for IPF."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • HSP90AA1 • TGFB1

Pimitespib in patients with advanced gastrointestinal stromal tumors in Japan: an expanded access program. (PubMed, Int J Clin Oncol) - "Pimitespib was well tolerated and effective in patients with advanced GIST in real-world practice in Japan. No new safety signals were identified."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Disorders • Oncology • Ophthalmology • Pain • Sarcoma

A Study of Pimitespib in Combination with Imatinib in Patients with GIST (CHAPTER-GIST-101) (clinicaltrials.gov) - P1 | N=78 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

A Study of Pimitespib in Combination with Imatinib in Patients with GIST (CHAPTER-GIST-101) (clinicaltrials.gov) - P1 | N=78 | Active, not recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

CHAPTER-Platform-201: Phase 2 trial of pimitespib plus enzalutamide for patients with metastatic castration-resistant prostate cancer. (ASCO-GU 2025) - "Pts who had received taxanes for mCRPC are excluded. Enrollment began in July 2023 and is currently ongoing."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CDC37 • HSP90AA1

Treatment patterns in patients with advanced gastrointestinal stromal tumor in Japan: An administrative claims database study. (ASCO-GI 2025) - "Tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib, and the HSP90 inhibitor, pimitespib have been approved for advanced GIST in Japan, but few studies have examined the nationwide trend in treatment patterns. This is the first real-world study to provide insights into the patient characteristics and current treatment patterns for advanced GIST in Japan. The treatment patterns are consistent with the Japanese Clinical Practice Guidelines."

Claims database • Clinical • Metastases • Stroma • Gastrointestinal Cancer • Oncology • CDC37

Combination of HSP90 Inhibitors and HSP70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis in Rabbits. (PubMed, Int J Mol Sci) - "We exposed New Zealand White Rabbits to hydrochloric acid (HCl, 0.1 N, 1.5 mL/kg), one of the top five chemicals most commonly involved in accidental exposures and inhalation injuries worldwide, and treated animals with either the orally available HSP90 inhibitor TAS-116 (1.7 mg/kg 5x/week) or TAS-116 combined with the HSP70 inducer, geranylgeranyl acetone (GGA, 50 mg/kg, 3x/week)...The use of HSP70 inducers may be a helpful tool to improve the profile of HSP90 inhibitors and reduce their minimal effective dose and side effects. Further investigation is required to explore the exact synergistic mechanism behind the antifibrotic profile of HSP90 inhibitors and HSP70 inducers."

Journal • Preclinical • Cardiovascular • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • CDC37

CHAPTER-GIST-101: A phase I study of pimitespib combined with imatinib in patients with imatinib-refractory gastrointestinal stromal tumor (ESMO Asia 2024) - P1 | "The ExP is a global, open-label, randomized part evaluating the efficacy and safety with PIMI + IM, PIMI monotherapy followed by IM re-challenging, and sunitinib (SU) in each arm of 20 pts. Exploratory pharmacogenomics analysis is also measured. The study recruits pts from Australia, China, Japan, Singapore, and Taiwan."

Clinical • P1 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • BRAF • CDC37 • KIT • PDGFRA

The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment. (PubMed, Cancer Immunol Res) - "Thus, pimitespib treatment combined with PD-1 blockade exhibited a far stronger antitumor effect than either treatment alone in animal models. Through these data, we propose that HSP90 inhibition is a promising therapeutic option for Treg cell-targeted cancer immunotherapy."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Gastric Cancer • Oncology • Solid Tumor • CD8 • CDC37 • FOXP3 • IL2 • STAT5

BrUOG 387: TAS-116 Plus Palbociclib in Breast and Rb-null Cancer (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Brown University | N=27 ➔ 0 | Trial completion date: Aug 2025 ➔ Aug 2024 | Recruiting ➔ Withdrawn

Enrollment change • Trial completion date • Trial withdrawal • Bladder Cancer • Breast Cancer • Endometrial Cancer • Eye Cancer • Genito-urinary Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Oncology • Retinal Disorders • Retinoblastoma • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • HER-2

A phase I study of PARP inhibitor (niraparib) plus HSP90 inhibitor (pimitespib) in solid tumors: The NiraPim (EPOC2102) study (ESMO 2024) - "Planned enrollment of 9-18 patients for the dose-escalation part and 30 patients for the dose-expansion part, from September 2022 to August 2024. The dose-escalation part has been completed, the RD has been determined, and the dose-expansion part has commenced."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRCA • CDC37 • HRD

Targeting HSP90 for Cancer Therapy: Current Progress and Emerging Prospects. (PubMed, J Med Chem) - "Notably, the selective inhibitor TAS-116 has already been successfully marketed. In this Perspective, we summarize the structure, biological functions, and roles of HSP90 in cancer, analyze the clinical status of HSP90 inhibitors, and highlight the latest advancements in novel strategies, offering insights into their future development."

Journal • Review • Oncology • Targeted Protein Degradation • CDC37 • HSP90AA1

Previously Unrecognized and Potentially Consequential Challenges Facing Hsp90 Inhibitors in Cancer Clinical Trials. (PubMed, Cell Stress Chaperones) - "It is likely why the oral Hsp90 inhibitor TAS-16 (Pimitespib), which bypasses blood circulation and other organs, showed some beneficiary efficacy by conveniently hitting tumors along the gastrointestinal track. The critical question is what the next step will be for Hsp90 chaperone as a cancer therapeutic target."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Targeted Protein Degradation • CDC37

CHAPTER-GIST-101: A phase I study of pimitespib combined with imatinib in patients with imatinib-refractory gastrointestinal stromal tumor. (ASCOBT 2024) - P1 | "The ExP is a global, open-label, randomized, part evaluating the efficacy and safety of PIMI in combination with IM, PIMI monotherapy, and standard therapy sunitinib (SU) in each arm of 20 pts. Exploratory pharmacogenomics analysis is also planned. After the DLT evaluation for the DEP, enrollment for the ExP began in March 2023 in Japan, Singapore, Taiwan and Australia, and for the DEP for Chinese pts is also ongoing in China to evaluate tolerability and efficacy of this combination."

Clinical • P1 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • BRAF • CDC37 • PDGFRA

Modulating the HSP90 control over NFκB/NLRP3/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: Insights into the role of TAS-116 (Pimitespib). (PubMed, Life Sci) - "Moreover, pimitespib induced the expression of HSP70, which could further contribute to the repression of fibrosis development. In summary, our findings provide an evolutionary perspective on managing liver fibrosis, positioning pimitespib as a promising candidate for anti-inflammatory and antifibrotic therapy."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • CASP1 • CDC37 • COL1A1 • HSP90AA1 • IL18 • IL1B • NLRP3 • TGFB1 • TIMP1 • TNFA

Pimitespib, a Novel Heat Shock Protein 90 Inhibitor, Is Effective in Treating Renal Cell Carcinoma by Anti-angiogenetic Signaling. (PubMed, Anticancer Res) - "PIM provides a novel approach for treating ccRCC and holds promise for future clinical strategies. Further in vivo and clinical research is required to elucidate the detailed relationship between the effects of PIM and ccRCC."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • CDC37 • EPAS1 • HIF1A • HSP90AA1 • VHL

Cardiovascular safety of pimitespib in patients with advanced solid tumors: An open-label, nonrandomized, phase 1 study. (PubMed, Cancer) - "Pimitespib is a new anticancer drug that is being used to treat cancer in the stomach or intestines (gastrointestinal stromal tumors). This study demonstrated that pimitespib had no marked effect on heart rhythm or negative effects on the heart or blood vessels and had promising anticancer effects in Japanese patients with advanced solid tumors who were unable to tolerate or benefit from standard treatment."

Clinical • Journal • Metastases • P1 data • Cardiovascular • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor