Fyarro (nanoparticle albumin-bound rapamycin) / EOC Pharma, Kaken Pharma - LARVOL DELTA

A Multicenter, Open-Label, Phase 2 Study of nab-Sirolimus (HB1901) Plus Endocrine Therapy in HR+/HER2- Advanced Breast Cancer Following Standard Therapy Failure (SABCS 2025) - P2 | "34 and 31 eligible patients were allocated to receive nab-Sirolimus 100 mg/m2 Q2W + fulvestrant or exemestane, respectively. Nab-sirolimus exhibited manageable toxicity and promising antitumor activity, particularly when combined with fulvestrant (achieving an ORR of 29% and a median PFS of 7.5 months). Nab-sirolimus + fulvestrant showed good efficacy in both PIK3CA/AKT1/PTEN altered and wild-type HR+ breast cancer patients. This novel mTOR inhibitor-based regimen may address the unmet need in CDK4/6i-failed HR+/HER2- advanced breast cancer."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

THE PATTERN.ORG SARCOMA CONSORTIUM: BUILDING A MULTI-INSTITUTIONAL DATA RESOURCE FOR THE SARCOMA RESEARCH COMMUNITY (CTOS 2025) - "Molecularly focused research has led to breakthroughs, notably afami-cel in synovial sarcoma and nab-sirolimus in PEComa... This pilot sarcoma data consortium project combined efforts from RCRF, UNC and PICI. These data offer some preliminary insights into the cohort, but we seek additional partners to facilitate a multi-institutional consortium around sarcoma sample and data collection and sharing. We plan to bring additional institutions in as we expand this resource in the coming year."

Clinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTLA4 • PD-1

A Phase I Trial of Combination Gemcitabine and Nab-Sirolimus in Advanced Leiomyosarcomas or Advanced Soft-Tissue Sarcomas With TSC2 or TSC1 Loss-of-function Mutations or Deletions (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Dose-escalation Study to Assess Safety and Pharmacokinetics of Nab-Sirolimus in Patients With Locally Advanced or Metastatic Solid Tumors and Moderate Liver Impairment (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Aadi Bioscience, Inc. | Trial completion date: Apr 2025 ➔ Aug 2026 | Trial primary completion date: Apr 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Solid Tumor

EEC-201: Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer (clinicaltrials.gov) - P2 | N=29 | Recruiting | Sponsor: Aadi Bioscience, Inc. | Trial completion date: Oct 2026 ➔ Jun 2027 | Trial primary completion date: Mar 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor

Pancreatic PEComas: Diagnostic Challenges and Divergent Clinical Outcomes (ACG 2025) - "Despite aggressive multimodal therapy, including chemotherapy (Gemcitabine, Docetaxel) and targeted treatment (nab-sirolimus), disease progression continued with hepatic metastases and severe gastrointestinal bleeding, requiring interventional radiological embolization procedures. Early surgical resection in Case 1 led to favorable long-term outcomes, whereas Case 2 demonstrates aggressive progression resistant to current therapies. These contrasting outcomes underscore the importance of early, accurate diagnosis, individualized therapeutic strategies, and further research into targeted therapies for aggressive PEComas."

Clinical • Clinical data • Back Pain • Gastroenterology • Gastrointestinal Cancer • Hepatocellular Cancer • Musculoskeletal Pain • Neuroendocrine Tumor • Pancreatic Cancer • Solid Tumor

THE STORY OF A SILENT TRAVELER: METASTATIC PERIVASCULAR EPITHELOID TUMORS (PECOMAS) (CHEST 2025) - "A shared decision was made to initiate immunotherapy with pembrolizumab over nab-sirolimus (mTOR-inhibitor). Malignant PEComa presents a diagnostic and therapeutic management challenge due to its rarity and the limited availability of high-quality clinical data. This case underscores the need for extensive multicenter studies to enhance clinical data for this disease. Additionally, this case illustrates the metastatic nature of malignant PEComas and its impact on the pulmonary system, which requires significant invasive pulmonary investigation and intervention."

Metastases • Gynecology • Lung Cancer • Oncology • Respiratory Diseases

A Case of Incidental Malignant PEComa in a Patient with Prostate Cancer (ACG 2025) - "Nab-sirolimus, an mTOR inhibitor, is the first FDA-approved agent for treating unresectable or metastatic malignant PEComas...Given the rarity of PEComas, accurate recognition of their histological and immunohistochemical features, combined with clinical context, is critical for optimal management. Close follow-up remains essential for detecting recurrence or metastasis.Figure: Image: high-grade spindle cell component of the malignant neoplasm (conventional hematoxylin-eosin stain).Figure: Image: uniform, strong immunoreactivity of tumor for melan-A."

Clinical • Gastrointestinal Disorder • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MLANA • SOX10 • TSC1 • TSC2

Albumin Nanoparticles in Cancer Therapeutics: Clinical Status, Challenges, and Future Directions. (PubMed, Pharmaceutics) - "The approval of Abraxane, an albumin-based nanoparticle formulation of paclitaxel, for metastatic breast cancer marked a significant milestone. However, further approvals have been slow to materialize until the recent approval of Fyarro® in 2021. This focused review highlights the potential of albumin-based nanoparticles, emphasizing their advantages, current state, and progress in clinical use as anticancer therapeutics. We also discuss challenges impeding new approvals and future directions for unlocking the full potential of this technology."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Safety and efficacy of nab-sirolimus (HB1901) + endocrine therapy in HR+/HER2- advanced breast cancer after standard therapy failure: A multicenter, open-label, phase 2 study (ESMO 2025) - P2 | "Results In the phase 2 study, 34 and 31 eligible pts were enrolled to receive nab-Sirolimus 100 mg/m 2 Q2W + fulvestrant or exemestane, respectively. Conclusions Nab-sirolimus exhibited manageable toxicity and promising antitumor activity, particularly when combined with fulvestrant (ORR 29%, PFS 7.4 mo). This novel mTOR inhibitor-based regimen may address the unmet need in CDK4/6i-failed HR+/HER2- advanced BC."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Seminal Abstract: PHASE 2 OPEN-LABEL MULTICENTER TRIAL OF NAB-SIROLIMUS + LETROZOLE IN ADVANCED/RECURRENT ENDOMETRIOID ENDOMETRIAL CANCER (IGCS 2025) - P2 | "Dual inhibition of mTOR and estrogen pathways with nab-sirolimus + letrozole has encouraging activity in chemotherapy naïve and exposed pts with advanced/recurrent low-grade EEC. Safety findings are consistent with each agent’s known profile. Further exploration of this non-chemotherapy approach is warranted."

Clinical • Metastases • P2 data • Endometrial Cancer • Oncology • Solid Tumor • ER • PGR • TP53

Phase II open-label multicenter trial of nab-sirolimus + letrozole in advanced/recurrent endometrioid endometrial cancer (ESMO 2025) - P2 | "Safety findings are consistent with each agent's known profile. Further exploration of this non-chemotherapy approach is warranted."

Clinical • Metastases • P2 data • Endometrial Cancer • Oncology • Solid Tumor • ER • PGR • TP53

SARC046: A Phase II Trial of Nab-Sirolimus in Patients With Progressing or Symptomatic Epithelioid Hemangioendothelioma (clinicaltrials.gov) - P2 | N=41 | Not yet recruiting | Sponsor: Sarcoma Alliance for Research through Collaboration

New P2 trial • Oncology

Metastatic recurrence of a masked uterine PEComa. (PubMed, Int J Gynecol Cancer) - No abstract available

Journal • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor

Phase 1 study of ABI-009 (nab-rapamycin) for surgically refractory epilepsy (RaSuRE). (PubMed, Epilepsia) - "ABI-009 was deemed safe and tolerable in a pediatric cohort with medically and surgically refractory epilepsy, establishing a maximum tolerated dose of 20 mg/m2 and showing early signs of efficacy."

Journal • P1 data • CNS Disorders • Epilepsy • Pediatrics • mTOR

Development, characterization, and in vitro evaluation of poly(ethylene oxide)-block-poly(ε-caprolactone)-α-tocopheryl succinate micelles as a novel nanocarrier for rapamycin delivery. (PubMed, Int J Pharm X) - "Currently, Fyarro® (Aadi Bioscience, Inc.), an albumin-bound nanoparticle formulation, is the only FDA-approved injectable rapamycin product...Minimal toxicity (≥70 % viability) was observed in normal human fibroblast cells (HFF1). These results point to the potential of PEO-b-PCL-α-TS micelles as a promising nanocarrier system, offering improved rapamycin solubility, enhanced stability, sustained release, and effective anticancer activity."

Journal • Preclinical • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Lung Cancer • Oncology • Solid Tumor

Clinical activity of immune checkpoint blockade in advanced perivascular epithelioid cell neoplasms (PEComas): A retrospective single center study. (ASCO 2025) - "While therapies targeting the mTOR pathway have shown promise, with nab-sirolimus being the first FDA-approved treatment for this histology, most patients will eventually progress...Most patients (78%) had previously received chemotherapy (gemcitabine and/or anthracycline, 54% each). ICIs included pembrolizumab (n = 5), nivolumab (n = 2), nivolumab-ipilimumab (n = 4), pembrolizumab-lenvatinib (n = 1) and nivolumab-bempegaldesleukin (n = 1)... The observed response rate of 23%, including two durable responses, suggests that ICIs may be an effective treatment option for a subset of PEComa patients, regardless of molecular profile. Further studies to identify predictive biomarkers and optimal sequencing with mTOR inhibitors and other therapies are warranted."

Checkpoint block • Checkpoint inhibition • IO biomarker • Metastases • Retrospective data • Gastrointestinal Disorder • Oncology • ATRX • FLT4 • NOTCH1 • RB1 • TFE3 • TP53 • TSC1 • TSC2

NCI-2018-01624: Nab-Sirolimus and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas (clinicaltrials.gov) - P1/2 | N=19 | Terminated | Sponsor: University of Washington | Trial completion date: Feb 2025 ➔ Jul 2024 | Active, not recruiting ➔ Terminated; Study was terminated at completion of the Phase 1 dose escalation due to loss of financial support.

Trial completion date • Trial termination • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation (KRYSTAL -19) (clinicaltrials.gov) - P1 | N=6 | Terminated | Sponsor: Mirati Therapeutics Inc. | N=79 ➔ 6 | Trial completion date: Jun 2026 ➔ Dec 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Dec 2024; Business objectives have changed

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Wolf in Sheep's Clothing: Taming Cancer's Resistance with Human Serum Albumin? (PubMed, Int J Nanomedicine) - "Drawing from clinical examples, including the success of albumin-bound paclitaxel (Abraxane) and new formulations like Pazenir and Fyarro (for Sirolimus), we identify gaps in current knowledge and propose strategies to optimize albumin-based systems. In conclusion, albumin-based nanoparticles, when tailored with appropriate modifications, have the potential to bypass multidrug resistance and improve the targeting of cancer cells. By enhancing albumin's ability to efficiently deliver therapeutic agents, these carriers represent a promising approach to addressing one of oncology's most persistent challenges, with substantial potential to improve cancer treatment outcomes."

Journal • Review • Oncology • ABCB1 • CD36 • SCARB1 • TFRC

Aadi Bioscience Announces Closing of $100 Million PIPE Financing (PRNewswire) - "Aadi Bioscience...announced the closing of its previously announced private placement. The private placement was led by Ally Bridge Group, with participation from new investors OrbiMed, Invus, Kalehua Capital and other accredited investors, Tae Han, co-founder of ProfoundBio, as well as existing investors, including Avoro Capital, KVP Capital and Acuta Capital Partners, for total gross proceeds of approximately $100 million....The proceeds from this private placement and the sale of Aadi's FYARRO business, together with Aadi's existing cash, cash equivalents and marketable securities, are expected to fund operations into 2028, including anticipated clinical data readouts for its ADC portfolio."

Commercial • Soft Tissue Sarcoma

Malignant Metastatic Pecoma Of The Vagina: Diagnostic And Therapeutic Challenges. Case Report And Literature Review. (ESGO 2025) - "The patient received treatment with nabsirolimus, and response was evaluated with a subsequent PET-CT that revealed a metabolic decrease of 77.6% with tumor size reduction as well as significant metabolic decrease of the metastasis.Results The standard treatment for gynecological PEComas is complete surgical resection with tumor-free margins as it provides the best local control and reduces the likelihood of recurrence...A key point to highlight is the need to initially rule out cervical involvement. Primary treatment is recommended based on complete tumor resection; if this is not feasible, alternative options such as mTOR inhibitors should be further explored."

Case report • Clinical • Metastases • Review • Gynecologic Cancers • Oncology • Vaginal Cancer • TSC1 • TSC2

Nab-Sirolimus and Endocrine Therapy in Recurrent Low Grade Serous Ovarian Cancer (NARETO) (clinicaltrials.gov) - P2 | N=37 | Recruiting | Sponsor: University of Oklahoma | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

Novel Therapeutics in Soft Tissue Sarcoma. (PubMed, Cancers (Basel)) - "Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with NTRK fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma...The challenges in drug development in soft tissue sarcoma are due to the rarity and the molecular heterogeneity of the disease and the fact that many subtypes are associated with complex karyotypes or non-targetable molecular alterations. We believe that progress maybe possible with a better understanding of the complex biology, the development of novel compounds for difficult targets such as proteolysis targeting chimeras (Protacs), the utilisation of modern clinical trial designs, and enhanced collaboration of academia with industry..."

Journal • Review • Angiosarcoma • Desmoid Tumors • Gastrointestinal Cancer • Gastrointestinal Disorder • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Targeted Protein Degradation • Undifferentiated Pleomorphic Sarcoma • HLA-A • MAGEA4 • NTRK

Nanoparticle Albumin-Bound Rapamycin, Temozolomide, and Irinotecan Hydrochloride in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Completed | Trial completion date: Sep 2025 ➔ Dec 2024

Trial completion • Trial completion date • Brain Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • AFP