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

Impact of KEAP1/STK11 co-mutations and NRF2 signaling on resistance to adagrasib in advanced NSCLC (AACR 2024) - P1, P1/2 | "Background: KRAS G12C inhibitors (G12Ci) are revolutionizing the therapeutic landscape of advanced NSCLC, but mechanisms of limited clinical efficacy observed in some patients (pts) merit continued exploration. Co-mutations in KEAP1 and STK11 and NRF2 signaling define a subgroup of KG12C NSCLC pts with markedly distinct outcomes upon treatment with ada. The mTORi and ada combination shows high efficacy for targeting KG12C NSCLC harboring KEAP1 and STK11 co-mutations. The clinical safety and efficacy of mTORi nab-sirolimus and ada will be determined in the ongoing KRYSTAL-19 trial (NCT05840510)."

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KEAP1 • KRAS • STK11

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

A Massively Peculiar Liver Mass: Examining the Clinical Presentation of a Patient With Perivascular Epithelioid Sarcoma of the Hepatic Portal Vein (ACG 2026) - "Nab-sirolimus was initiated prior to the patient being rehospitalized with rapid disease progression...Figure: MRI in the axial plane with T1 weighting showing numerous hepatic parenchymal PEComa lesions. Figure: MRI in the coronal plane with T1 weighting showing the primary PEComa arising from the porta hepatis with numerous hepatic parenchymal PEComa lesions."

Clinical • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Failure • Rhabdomyosarcoma • Sarcoma • Septic Shock • Soft Tissue Sarcoma • Solid Tumor • CTSK • GPC3 • TFE3

NET-202: Trial of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors (clinicaltrials.gov) - P2 | N=12 | Completed | Sponsor: Aadi Bioscience, Inc. | Recruiting ➔ Completed | N=21 ➔ 12 | Trial primary completion date: May 2025 ➔ Oct 2025

Enrollment change • Trial completion • Trial primary completion date • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Solid Tumor

A Phase 2 Study of Sirolimus for Injection (Albumin-bound) in Patients With Progressive or Symptomatic Epithelioid Hemangioendothelioma (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

New P2 trial • Oncology

Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1 or TSC2 Genes (PRECISION 1) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Aadi, LLC | Not yet recruiting ➔ Recruiting | N=180 ➔ 120

Enrollment change • Enrollment open • Pan tumor • Oncology • Solid Tumor • TSC1 • TSC2

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

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

SARC046: A phase II trial of nab-sirolimus in patients with progressing or symptomatic epithelioid hemangioendothelioma. (ASCO 2026) - P2 | "Nab-sirolimus is albumin bound sirolimus, which achieves higher intratumoral accumulation compared to oral sirolimus and has demonstrated increased antitumor activity in preclinical cancer models compared to the oral mTOR inhibitors sirolimus and everolimus. Planned post hoc subgroup analyses will include outcomes by fusion type and presence of serosal effusions at the time of study enrollment. The trial is registered at clinicaltrials.gov NCT07104331."

Clinical • P2 data • Oncology • Sarcoma • Solid Tumor • CAMTA1 • TFE3

Phase I trial of combination gemcitabine (gem) and nab-sirolimus (nab-S) in advanced leiomyosarcomas (LMS) or advanced soft-tissue sarcomas (STS) with TSC1/2 alterations: Preliminary results. (ASCO 2026) - P1 | "The MTD was determined to be gem 900mg/m2 with nab-s 100mg/m2 on Days 1 and 15 of a 28-day cycle. Based on this preliminary safety and efficacy, an expansion with an additional 6 pts at this DL is ongoing."

Metastases • P1 data • Hematological Disorders • Leiomyosarcoma • Mucositis • Pneumonia • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Thrombocytopenia • TSC1

Liver Transplantation After Prolonged Nab-Sirolimus Therapy for Unresectable Hepatic Perivascular Epithelioid Cell Tumor With Bilobar Involvement. (PubMed, ACG Case Rep J) - "She underwent right trisegment orthotopic liver transplantation, and the explant showed a well-circumscribed PEComa without vascular invasion or additional lesions. This case highlights prolonged nab-sirolimus as a bridge to transplantation in selected patients with favorable tumor biology."

Journal • Hepatology • Oncology • Transplantation

Correlation of nab-sirolimus tumor drug levels and improved tumor suppression in KRAS G12C non-small cell lung cancer xenografts treated with nab-sirolimus in combination with KRAS inhibitors (AACR 2024) - "KRAS G12C inhibitors (KRAS G12Cis), sotorasib and adagrasib, are approved for the treatment of KRAS G12C-mutated, locally advanced or metastatic NSCLC. The addition of a KRAS G12Ci to nab-sirolimus significantly reduced tumor volume and increased tumor drug levels, suggesting enhanced tumor targeting compared with everolimus plus KRAS G12Cis and correlating to improved antitumor activity and mTOR target suppression. Clinical dose-finding studies are needed to determine potential drug-drug interactions between nab-sirolimus and KRASis."

Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • STK11

Evaluation of nab-sirolimus in combination with fulvestrant or PI3K pathway inhibitors to overcome resistance in breast cancer cell lines (AACR 2024) - "This is mitigated by mTOR inhibition as demonstrated by improved outcomes with exemestane plus the mTOR inhibitor (mTORi) everolimus in pts with HR+ advanced BC...MDA-MB-361 cells or HR-negative (HR−), PI3K-mutated BC cells, MDA-MD-453, were incubated for 5 days with increasing concentrations of nab-sirolimus and PI3K-AKT-mTOR pathway inhibitors gedatolisib or alpelisib... nab-Sirolimus enhanced the cytotoxic effects of fulvestrant in HR+ BC cells and of PI3Kis in HR+ and HR− BC cells. Addition of nab-sirolimus to ET or other PI3K-AKT-mTOR pathway inhibitors may overcome mechanisms of resistance; further exploration is warranted to elucidate clinical relevance."

Combination therapy • Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • EIF4EBP1 • ER • PIK3CA

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

Enrollment open • Oncology

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=18 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting

Enrollment open • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TSC1 • TSC2

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=18 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | N=12 ➔ 18

Enrollment change • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TSC1 • TSC2

A plain language summary of the AMPECT study: nab-sirolimus for advanced malignant perivascular epithelioid cell tumors. (PubMed, Future Oncol) - No abstract available

Journal • Oncology • Sarcoma • Solid Tumor

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