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Do Your Oncology Patients Needing Next Line Treatment Have a TSC1 or TSC2 Mutation?

These Mutations Occur Across Multiple Solid Tumor Types¹ and Represent a Potential Target for an Investigational Treatment.

PRECISION 1 is a clinical trial for an investigational mTOR inhibitor in patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes.²

Does your patient have one of these mutations?
Find Out

About nab-Sirolimus

nab-Sirolimus is an mTOR inhibitor that uses nanoparticle albumin-bound (nab) technology engineered to deliver high levels of drug directly to proliferating tumors, which may result in slower tumor growth in patients with TSC1 and TSC2 inactivating alterations.³

The safety and efficacy of nab-sirolimus in this setting has not been established.

mTOR=mechanistic target of rapamycin; nab=nanoparticle albumin-bound; TSC1=tuberous sclerosis 1; TSC2=tuberous sclerosis 2.

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What is PRECISION 1?

PRECISION 1 is a clinical trial investgating nab-sirolimus in cancer patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes.²

The safety and efficacy of nab-sirolimus in this setting has not been established.

PRECISION 1 is a prospective, phase 2, open-label, tumor-agnostic, multicenter basket trial for patients aged 12 years or older with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes, which are tumor suppressor genes and are upstream regulators of mTOR.^2,4,5

The primary objective of the study is to determine the overall response rate (ORR) in patients harboring pathogenic inactivating alterations in TSC1 or TSC2 genes.¹

Visit clinicaltrials.gov to see the secondary outcome measures

mTOR=mechanistic target of rapamycin; nab=nanoparticle albumin-bound; TSC1=tuberous sclerosis-1; TSC2=tuberous sclerosis-2.

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

Are your patients eligible for PRECISION 1?

TSC1 and TSC2 inactivating alterations can be detected through next-generation sequencing (NGS) of tumor tissue or liquid biopsy. Patients who have already received an NGS report of their tumor profile do not require an additional biopsy to be considered for PRECISION 1.²

Key Eligibility Criteria

12 years old
Naive to mTOR inhibitors
ECOG PS 0 or 1 (or KPS 80 or LPPS 80 for pediatrics)
Centrally confirmed TSC1 or TSC2 pathogenic inactivating alteration
Metastatic or locally advanced solid tumors ineligible for surgery
Measurable disease
Failed standard therapies appropriate for their tumor type

Learn more about eligibility requirements at clinicaltrials.gov

ECOG PS=Eastern Cooperative Oncology Group performance status; KPS=Karnofsky performance status;
LPPS=Lansky-Play Performance Scale; mTOR=mechanistic target of rapamycin; TSC1=tuberous sclerosis 1; TSC2=tuberous sclerosis 2

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

What are TSC1 and TSC2 inactivating alterations?

What are TSC1 and TSC2 inactivating alterations?

TSC1 and TSC2 are tumor suppressor genes downstream in the mTOR pathway. Alterations in these genes may resut in mTOR pathway overactivation, which prompts uncontrolled cell growth, metabolic changes, and enhanced survival.^4-6

Currently, there are no drugs approved to treat patients with malignant tumors specifically harboring TSC1 or TSC2 inactivating alterations.^7-11

Alterations or deletions in TSC1 or TSC2 genes have been identified in multiple tumor types throughout the body, in percentages up to 8%.¹

Affected organ
Percent with TSC1 or TSC2 mutation
Bladder
8.03%
Hepatobiliary
4.58%
Endometrial
3.32%
Soft tissue sarcoma.
2.99%
Ovarian
2.77%

Affected organ
Percent with TSC1 or TSC2 mutation
Esophagogastric
2.11%
Kidney
1.96%
NSCLC
1.93%
Melanoma
1.82%
CRC
1.38%

AACR=American Association for Cancer Research; mTOR=mechanistic target of rapamycin; TSC1=tuberous sclerosis-1; TSC2=tuberous sclerosis-2

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

What is nab-sirolimus?

nab-Sirolimus is an mTOR inhibitor that uses nanoparticle albumin-bound (nab) technology. Based on preclinical data, nab technology enhances tumor penetration and drug accumulation due to the preferential accumulation of albumin in proliferating tumors.³ In preclinical studies, this enhanced accumulation resulted in slowed tumor growth.³

The safety and efficacy of nab-sirolimus for the treatment of solid tumors harboring TSC1 or TSC2 mutations has not been established.

mTOR=mechanistic target of rapamycin; TSC1=tuberous sclerosis-1; TSC2=tuberous sclerosis-2.

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

About Aadi Bioscience

At Aadi Bioscience, our mission is to improve the lives of people with mTOR-driven diseases. We believe success depends on addressing the limitations of current mTOR inhibitors and leveraging the latest genomic profiling technology to identify the patients most likely to benefit from mTOR inhibition

Learn more about Aadi Bioscience.

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

A Message from a PRECISION 1 Investigator

It is an exciting time to be practicing clinical oncology. Over the past 20 years, there have been tremendous advances in our understanding of cancer genomics, with researchers working to characterize genetic differences among tumors.

I am excited to be working with Aadi Biosciences on the PRECISION 1 trial, which is studying nab-sirolimus in cancer patients with various tumor types that have mutations in the TSC1 or TSC2 genes. The safety and efficacy of nab-sirolimus in this setting has not been established.

As our understanding of cancer genomics continues to grow, it is becoming increasingly important to utilize next generation sequencing (NGS) to fully understand each patient’s precise tumor type. Armed with the knowledge, we may have a greater chance to match the patient to an appropriate treatment.

TSC1=tuberous sclerosis 1; TSC2=tuberous sclerosis 2

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

How to enroll patients in PRECISION 1

Please contact Aadi Bioscience for more information on PRECISION 1, including how to enroll a patient.

How to enroll patients in PRECISION 1

Please contact Aadi Bioscience for more information on PRECISION 1, including how to enroll a patient.

Contact Aadi Bioscience

First Name*

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or a Patient/Caregiver?*

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The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

Find a Trial Site

Choose your state to find a PRECISION 1 trial site near your patient.

If you don’t see a site near your patient, please contact Aadi Bioscience at info@aadibio.com. We may be able to establish a site with support from our network of clinical partners.

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.

References

Gulati GS, et al. Presented at: American Association for Cancer Research Annual Meeting; April 8–13, 2022; New Orleans, LA. Poster 5799.
Phase 2 basket trial of nab-sirolimus in patients with solid tumors with pathogenic alterations in TSC1 or TSC2 genes (PRECISION 1). ClinicalTrials.gov Identifier: NCT05103358. Updated April 6, 2023. Accessed April 6, 2023. https://clinicaltrials.gov/ct2/show/NCT05103358?term=NCT05103358&draw=2&rank=1
Wagner AJ, Ravi V, Riedel RF, et al. nab-Sirolimus for patients with malignant perivascular epithelioid cell tumors. J Clin Oncol. 2021;39(33):3660-3670JCO2101728. doi:10.1200/JCO.21.01728
Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004;18(16):1926-1945. doi:10.1101/gad.1212704
Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell. 2017;169(2):361-371. doi:10.1016/j.cell.2017.03.035
Gonzalez-Angulo AM, Meric-Bernstam F, Chawla S, et al. Weekly nab-rapamycin in patients with advanced nonhematologic malignancies: final results of a phase I trial. Clin Cancer Res. 2013;19(19):5474-5484. doi:10.1158/1078-0432.CCR-12-3110
TSC1 studies. ClinicalTrials.gov. Accessed February 28, 2022. https://clinicaltrials.gov/ct2/results?cond=tsc1&term=&cntry=&state=&city=&dist=
TSC2 studies. ClinicalTrials.gov. Accessed February 28, 2022. https://clinicaltrials.gov/ct2/results?cond=tsc2&term=&cntry=&state=&city=&dist=
Kim JW, Milowsky MI, Hahn NM, et al. Sapanisertib, a dual mTORC1/2 inhibitor, for TSC1- or TSC2-mutated metastatic urothelial carcinoma (mUC). Meeting abstract presented virtually at: Genitourinary Cancers Symposium; February 11-13, 2021. Accessed February 28, 2022. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.6_suppl.431
Afinitor. Prescribing information. Novartis Pharmaceuticals Corporation; 2022. Accessed February 28, 2022. https://www.novartis.us/sites/www.novartis.us/files/afinitor.pdf
Zortress. Prescribing information. Novartis Pharmaceuticals Corporation; 2021. Accessed February 28, 2022. https://www.novartis.us/sites/www.novartis.us/files/zortress.pdf

The safety and efficacy of nab-sirolimus in patients with tumors harboring TSC1 or TSC2 mutations have not been established.