Algorithm-Based Treatment Options for Advanced Breast Cancer

Overseen By Padma S Rajagopal, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Visceral crisis, Symptomatic brain metastases, Cardiac conditions, Lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to identify treatments for aggressive breast cancer types. Researchers are testing an algorithm called ENLIGHT to determine if it can suggest better drug options for cancers that are difficult to treat or have recurred. Participants with either triple-negative or hormone therapy-resistant breast cancer, which has not responded to treatment or has returned, might be suitable candidates. The trial will use ENLIGHT to guide treatment choices and assess whether this approach can improve outcomes. As an unphased trial, this study provides patients the opportunity to contribute to pioneering research that could lead to more effective treatments for challenging breast cancer cases.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that participants may remain on treatment during the initial screening and testing phase if their current treatment is no longer beneficial. It's best to discuss your specific situation with the trial team.

What prior data suggests that the ENLIGHT algorithm is safe for selecting breast cancer treatments?

Research has shown that the ENLIGHT system assists doctors in selecting the best treatment based on the genetic details of a patient's tumor. This system uses advanced technology to predict which drugs might work best for each individual. Although ENLIGHT is not a drug, it helps choose drugs already approved by the FDA.

Regarding safety, the drugs selected by ENLIGHT have received FDA approval, indicating they have been tested in previous studies and found safe for certain uses. However, when used for different conditions, such as aggressive breast cancer, there might be less information about their safety. Still, their FDA approval for other uses provides some confidence in their safety. For concerns or questions about the specific drugs recommended, patients should discuss them with healthcare providers who can offer more details on potential side effects and what to watch for. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatment options for advanced breast cancer because they are personalized to the genetic makeup of the tumor. Unlike standard treatments that often use a one-size-fits-all approach, these options use genomic and transcriptomic markers to guide therapy, potentially leading to more effective and tailored results. The ENLIGHT treatment, in particular, uses a sophisticated algorithm to match patients with the best possible treatment based on their tumor's specific genes and proteins. This personalized approach could improve outcomes and reduce unnecessary side effects by ensuring patients receive the most compatible therapy for their cancer type.

What evidence suggests that this algorithm is effective for advanced breast cancer?

Research has shown that ENLIGHT can greatly enhance the selection of treatments for aggressive cancers. In this trial, participants may receive treatments matched by ENLIGHT, which studies have found to more than double the likelihood of responding to therapy. In another study, the average time during which the cancer did not worsen was 12 months, with 64% of patients benefiting. ENLIGHT has proven to be a reliable tool for predicting patient responses to various treatments. It analyzes genetic and other biological information from the tumor to identify effective treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Padma S Rajagopal, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults with aggressive breast cancer that's either triple-negative or resistant to hormone therapy, and hasn't improved or has returned after treatment. Participants must be over 18 years old.

Inclusion Criteria

Willingness to comply with required study procedures and visits.

Participant tumor subtypes will be enrolled as follows: TNBC Cohort, Endocrine-Refractory Cohort.

Participants must have measurable disease per RECIST v1.1.

Exclusion Criteria

Participants with uncontrolled intercurrent illness or situations that would limit compliance with study requirements.

Participants with positive pregnancy test, unable to provide tissue specimens of sufficient quality.

I do not have an urgent health crisis due to cancer in my organs, brain, or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive treatment based on the ENLIGHT algorithm recommendations, with follow-up visits every 2 cycles until disease progression or treatment completion

Up to 2 years

Every 2 cycles (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with health checks every 3 months for 2 years

2 years

Every 3 months (virtual or in-person)

What Are the Treatments Tested in This Trial?

Interventions

• ENLIGHT

Trial Overview The SYNTHESIS-Breast trial tests if the ENLIGHT algorithm can identify effective FDA-approved drugs for difficult-to-treat breast cancers. Patients' tumors are analyzed and based on results, they're assigned to continue standard care or receive recommended treatments at NIH.

How Is the Trial Designed?

Group I: 3/Transcriptomic Match Experimental Treatment 3 Interventions

Treatment regimen as selected by transcriptomic algorithm; treatment to be directed by NIH study team with requirement for treatment at NIH

Group II: 2/Genomic Marker Associated with FDA-Approved On-Label Treatment Experimental Treatment 3 Interventions

Treatment in accordance with genomic marker; treatment to be directed locally by referring/treating physician

Group III: 1/No Recommended Match Active Control 3 Interventions

Treatment per physician's choice

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10029756/

Clinically oriented prediction of patient response to ... ENLIGHT can predict treatment response across multiple therapies and cancer types better than published biomarkers, and it can potentially enhance clinical ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2632

Validation of ENLIGHT, an AI predictor of immune ... We first established the value of ENLIGHT as a predictive biomarker using the BIO2 pre-treatment samples. EMS-NGS was a superior predictive ...

3. biorxiv.org biorxiv.org/content/10.1101/2022.02.27.481627v2.full

Clinically oriented prediction of patient response to ... In sum, in this retrospective study, ENLIGHT demonstrably enhances the ability to predict therapeutic response across multiple cancer types from ...

4. researchgate.net researchgate.net/figure/The-ENLIGHT-pipeline-and-its-tuning-for-personalized-oncology-A-ENLIGHTs-pipeline_fig1_366207745

The ENLIGHT pipeline and its tuning for personalized ... The median PFS on MTA was 12.0 months and the median PFSratio in patients receiving MTA as >1 line of treatment was 2.71, with a benefit rate of 64%. OS was ...

5. drugdiscoverytrends.com drugdiscoverytrends.com/pangea-biomed-enlight-dp-precision-oncology-tumor-image-analysis/

Pangea predicts cancer treatment response from tumor images In the study, patients who received ENLIGHT-matched treatments showed a 2.28 times higher likelihood of responding to therapy compared to those ...

6. cell.com cell.com/med/pdf/S2666-6340(22)00455-X.pdf

Clinically oriented prediction of patient response to ... describe ENLIGHT, a transcriptomics-based computational approach that identifies clinically relevant genetic interactions from the tumor.

7. linkmedicalsolutions.com linkmedicalsolutions.com/medical-technologies/oncology/enlight-drug-response-prediction/patients/

ENLIGHT A New New Era in Personalised Cancer Care ENLIGHT uses AI and transcriptomics to analyse your tumour at a deeper genetic level, allowing your doctor to choose therapies tailored to your biology ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S266663402200455X

Clinically oriented prediction of patient response to ... ENLIGHT, a computational tool based on cancer gene expression profiles that aims at predicting the most appropriate drug and their dose for each patient.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11957836/

Hallmarks of artificial intelligence contributions to precision ... In this Review, we discuss ten AI hallmarks in precision oncology, organized into three groups: (1) cancer prevention and diagnosis, encompassing cancer ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT05312411

NCT05312411 | A Phase I Feasibility And Safety Study of ... The purpose of this study is to see if a new treatment could help patients who have osteosarcoma that does not go away with treatment (is refractory) or comes ...