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

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

Aadi to Sell FYARRO for $100 Million, Cumulative Capital Expected to Fund Operations into Late 2028 (PRNewswire) - "In a separate agreement, KAKEN Pharmaceutical...has entered into a stock purchase agreement under which KAKEN will acquire Aadi Subsidiary, Inc. and all of its assets, including FYARRO (sirolimus protein-bound particles for injectable suspension) (albumin-bound) and associated infrastructure, including the majority of Aadi employees who support the FYARRO business. FYARRO is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa), with cumulative revenue of $25.2 million reported over the prior four quarters ended September 30, 2024. Per the terms of the agreement, Kaken will pay Aadi $100 million in cash at closing, subject to certain adjustments. The transaction is expected to close in the first half of 2025....KAKEN will also acquire the rights to the Aadi name and trademark."

M&A • Solid Tumor

Activity of nab-Sirolimus Alone or in Combination with Cabozantinib, Octreotide, or Talazoparib in Nonclinical Neuroendocrine Tumor Models (NANETS 2024) - "nab-Sirolimus, an injectable form of albumin-bound sirolimus, demonstrates greater tumor drug accumulation, mTOR target inhibition, and antitumor activity in human tumor models compared to conventional mTOR inhibitors including everolimus...in vivo activity in NET lines. Combinations o. nab-sirolimus with other targeted agents demonstrated additive anti-proliferative and antitumor activity; however, the magnitude of response for select combinations compared with single agent activity warrants further investigation."

Combination therapy • Preclinical • Endocrine Cancer • Gastrointestinal Disorder • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • STC1

Phase 2 study of nab-sirolimus in patients with well-differentiated and advanced/metastatic neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas (NANETS 2024) - P2 | "Everolimus, an oral mTOR inhibitor (mTORi), is an option for treatment of NETs of the GI tract, lung, or pancreas, but response rates observed in the RADIANT-3 and -4 studies were modest at 4--10%. CONCLUSIONS Stage 1 of enrollment is currently open. The criterion has been met for continuing to Stage 2 of enrollment."

Clinical • Metastases • P2 data • Endocrine Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • TSC1 • TSC2

A Phase 1 Study of ABI-009 (Nab-sirolimus) in Combination With Temozolomide and Irinotecan in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors-A Children's Oncology Group Pediatric Early Phase Clinical Trial Network Study ADVL1514. (PubMed, Cancer Med) - P1 | "The MTD for Nab-sirolimus was 15 mg/m2/dose IV on D1 and D8 in combination with temozolomide 125 mg/m2/dose and oral irinotecan 90 mg/m2/dose daily for 5 days during 21D cycles."

Combination therapy • Journal • P1 data • Brain Cancer • CNS Tumor • Ewing Sarcoma • Hematological Disorders • Oncology • Pediatrics • Sarcoma • Solid Tumor • Thrombocytopenia

Aadi Bioscience Announces Financial Results for the Third Quarter 2024 and Provides Corporate Update (PRNewswire) - "FYARRO net product sales were $7.2 million in the third quarter, an increase of 17 percent from Q2 2024 and 21 percent compared to the prior-year period...Aadi completing wind-down of the PRECISION1 trial of nab-sirolimus in patients with solid tumors harboring TSC1 or TSC2 inactivating alterations. All patients who were still receiving benefit at the time the study was halted were transitioned to an expanded access protocol, and a report out of the PRECISION1 trial is expected to be provided in 2025. The Phase 2 trials of nab-sirolimus for advanced or recurrent endometrioid-type endometrial cancer (EEC) and neuroendocrine tumors (NETs) enrolled 24 and 12 patients, respectively. Both studies enrolled sufficient patients to assess initial efficacy signals later this year."

P2 data • Sales • Endometrial Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

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

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

A PHASE 2, OPEN-LABEL, SINGLE-ARM, PROSPECTIVE, MULTICENTER STUDY OF NAB-SIROLIMUS PLUS LETROZOLE IN ADVANCED OR RECURRENT ENDOMETRIOID ENDOMETRIAL CANCER (IGCS 2024) - P2 | "Exploratory endpoints include correlation of biomarkers with clinical outcomes. Current Trial Status: The trial is currently open for enrollment."

Clinical • Metastases • P2 data • Endometrial Cancer • Oncology • Solid Tumor • PTEN

Aadi Bioscience Provides PRECISION1 Trial and Corporate Updates (PRNewswire) - "Aadi Bioscience...announced it will halt the registration-intended PRECISION1 trial of nab-sirolimus in patients with solid tumors harboring TSC1 or TSC2 inactivating alterations. An analysis by the Independent Data Monitoring Committee demonstrated that the study was unlikely to exceed an efficacy threshold necessary to support an accelerated approval....The approximately 25 patients in PRECISION1 who are still benefiting from nab-sirolimus will be eligible for transition to a planned expanded access protocol, and a complete analysis of the PRECISION1 trial will be provided at a later date....Aadi will pause new enrollment, but continue dosing previously enrolled patients, in two, ongoing Phase 2 trials of nab-sirolimus for advanced or recurrent endometrioid-type endometrial cancer (EEC) and neuroendocrine tumors (NETs). Both studies have enrolled sufficient patients (n=20 and n=10 for EEC and NETs, respectively) to assess initial efficacy signals later this year."

DSMB • P2 data • Trial termination • Endometrial Cancer • Neuroendocrine Tumor

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 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Aadi Bioscience Announces Financial Results for the Second Quarter 2024 and Provides Corporate Update (PRNewswire) - "FYARRO net product sales were $6.2 million in the second quarter, an increase of 15 percent from Q1 2024 and in line with the prior year period. Two-thirds interim analysis of registration-intended PRECISION1 trial is planned for Q3 2024. PRECISION1 is exploring nab-sirolimus in solid tumors with TSC1 or TSC2 inactivating alterations. The trial is fully enrolled, and study completion is expected by year-end. Enrollment into two additional Phase 2 trials is ongoing, with initial data expected by the end of the year. These tumor specific, open-label trials are investigating the potential of nab-sirolimus for difficult-to-treat mTOR-driven cancers: advanced or recurrent endometrioid-type endometrial cancer (EEC) in combination with letrozole, and neuroendocrine tumors (NETs) of the lung, gastrointestinal tract and pancreas."

P2 data • Sales • Trial status • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

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

New P2 trial • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • 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=79 | Active, not recruiting | Sponsor: Mirati Therapeutics Inc. | Phase classification: P1/2 ➔ P1

Combination therapy • Metastases • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Antitumor activity of nab-sirolimus versus mTOR inhibitors temsirolimus, sirolimus, and everolimus in A549 NSCLC xenografts. (ASCO 2024) - "nab-Sirolimus resulted in significantly higher intratumoral drug concentration, stronger inhibition of mTOR targets, and greater antitumor activity compared to other IV and oral mTORis in a KRAS/STK11/KEAP1 mutated NSCLC xenograft model. These results support further clinical evaluation of nab-sirolimus as a single agent or in combination with other therapeutic agents in oncology."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EIF4EBP1 • KEAP1 • KRAS • PIK3CA • PTEN • STK11 • TSC1 • TSC2

A phase 2, open-label, single-arm, prospective, multicenter study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer. (ASCO 2024) - P2 | "Exploratory endpoints include correlation of baseline molecular biomarkers with clinical outcomes. The trial is open for enrollment."

Clinical • IO biomarker • Metastases • P2 data • Endometrial Cancer • Oncology • Solid Tumor • ER • PTEN

Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1) (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Aadi Bioscience, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Pan tumor • Oncology • Solid Tumor • TSC1 • TSC2