RYZ101 Alone and with Pembrolizumab for Breast Cancer

(TRACY-1 Trial)

Recruiting at 24 trial locations

Overseen By RayzeBio Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: RayzeBio, Inc.

Disqualifiers: Cardiovascular disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, RYZ101 (also known as 225Ac-DOTATATE), both alone and with Pembrolizumab, for a specific type of breast cancer. The goal is to determine if RYZ101 can treat breast cancer that cannot be surgically removed or has metastasized, particularly when cancer cells have specific receptors (SSTRs) that can be targeted. Participants should have ER+ (estrogen receptor positive), HER2-negative breast cancer that has spread and cannot be cured with current treatments. This trial is particularly suited for those who can identify a measurable tumor on an SSTR-PET scan and have not succeeded with other cancer therapies. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking cancer therapy development.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RYZ101 (225Ac-DOTATATE) has generally been well-tolerated in earlier studies. Researchers are studying its ability to target and destroy cancer cells while sparing nearby healthy cells. This precision may lead to fewer side effects compared to less targeted treatments.

The FDA has already approved pembrolizumab for treating various cancers, including some types of breast cancer. It is widely used and generally well-tolerated, though some patients might experience side effects like tiredness or skin reactions.

The trial is in its early stages, so researchers are still determining the safest dose and checking for any new or unexpected side effects. Overall, both treatments have shown promise in terms of safety, but ongoing studies will provide more detailed information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for breast cancer, which typically involve chemotherapy, hormone therapy, or HER2-targeted drugs, RYZ101 uses a novel approach by incorporating 225Ac-DOTATATE, a radioisotope therapy. This treatment delivers targeted radiation directly to cancer cells, potentially minimizing damage to healthy tissue. Researchers are excited about RYZ101 because it may offer a more precise and effective way to attack tumors, especially when combined with Pembrolizumab, an immunotherapy drug that helps the immune system better recognize and fight cancer cells. This combination could enhance the overall response rate and improve outcomes for patients with breast cancer.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Studies have shown that RYZ101 (225Ac-DOTATATE) can precisely target cancer cells, releasing energy to destroy even a single cancer cell without harming nearby healthy cells. This treatment has shown promise in patients with estrogen receptor-positive (ER+), HER2-negative breast cancer, particularly when the cancer is advanced or inoperable. In this trial, researchers will test RYZ101 both alone and in combination with pembrolizumab, an existing cancer treatment. Early research suggests that RYZ101 can be effective on its own and may work even better with pembrolizumab. These promising early results have generated excitement about its potential. ^{1 2 3 4 5}

Who Is on the Research Team?

Denis Ferreira, MD

Principal Investigator

RayzeBio, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with ER+, HER2-negative breast cancer that can't be removed by surgery or has spread to other parts of the body. Participants must have tumors expressing SSTRs, a type of receptor.

Inclusion Criteria

I can perform daily activities with minimal assistance.

My blood, liver, and clotting tests are normal.

I have a tumor that can be measured and shows up on a specific PET scan.

Exclusion Criteria

History of hypersensitivity to specific agents

I have a serious heart condition.

I have previously undergone radiation therapy, including radioembolization.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RYZ101 treatment with dose escalation over 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• 225Ac-DOTATATE (RYZ101)
• Pembrolizumab

Trial Overview The study is testing RYZ101, a targeted radiation therapy, both alone and combined with pembrolizumab, an immunotherapy drug. It's in early stages (Phase 1b/2) to see how safe it is and how well it works.

How Is the Trial Designed?

Group I: Expansion Experimental Treatment 1 Intervention

RYZ101 RP2D Regimen

Group II: Dose Escalation Experimental Treatment 1 Intervention

RYZ101 Dose Level -1 RYZ101 Dose Level 1 RYZ101 Dose Level 2 RYZ101 Dose Level 3

Who Is Running the Clinical Trial?

RayzeBio, Inc.

Lead Sponsor

Trials

6

Recruited

540+

Published Research Related to This Trial

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

Pembrolizumab significantly improved progression-free survival (PFS) in patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer, with a median PFS of 16.5 months compared to 8.2 months for standard chemotherapy, indicating its efficacy as a first-line treatment.

The FDA found no safety concerns during the approval process, and while both pembrolizumab and standard of care had similar adverse reactions, the duration of treatment with pembrolizumab was nearly double that of standard care, suggesting a potentially more favorable treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. Casak, SJ., Marcus, L., Fashoyin-Aje, L., et al.[2022]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a study of 1,026 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, pembrolizumab showed an objective response rate of 44.5%, with median progression-free survival of 7.9 months and overall survival of 17.2 months.

Higher PD-L1 expression (≥90%) was linked to better treatment outcomes, while factors like poor performance status and the presence of bone or liver metastases were associated with worse clinical outcomes, indicating the importance of patient selection for pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cortellini, A., Tiseo, M., Banna, GL., et al.[2020]

Pembrolizumab, a biologic agent used for treating non-small cell lung cancer, can cause immune-related adverse effects (irAEs) that may persist even after the drug is no longer detectable in the bloodstream, indicating a prolonged immune response.

A case study of a 72-year-old patient revealed that pembrolizumab's clearance rate changes from linear to non-linear after about 77 days, suggesting that current fixed dosing strategies may need to be reassessed to account for the drug's complex pharmacokinetics and the potential for prolonged toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Pharmacokinetics of pembrolizumab in a patient with stage IV non-small cell lung cancer after a single 200 mg administration. de Vries, F., Smit, AAJ., Wolbink, G., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a phase Ib trial (KEYNOTE-028) involving 43 patients with advanced anal carcinoma, pembrolizumab showed a manageable safety profile, with 64% experiencing treatment-related adverse events, but no treatment-related deaths or discontinuations.

Among patients with PD-L1-positive tumors, pembrolizumab achieved a 17% overall response rate and a 58% disease control rate, indicating promising antitumor activity and supporting further research in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ott, PA., Piha-Paul, SA., Munster, P., et al.[2021]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS3184

RYZ101 ( 225 Ac-DOTATATE) in patients with estrogen ... Available data support investigating the efficacy of RYZ101 in patients with ER-positive, HER2-negative, locally advanced and unresectable or metastatic breast ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P4-10-02/752584/Abstract-P4-10-02-RYZ101-225Ac-DOTATATE

Abstract P4-10-02: RYZ101 (225Ac-DOTATATE ... Available data support investigating the efficacy of RYZ101 ... Clinical and genomic factors associated with elacestrant outcomes in ESR1-mutant ...

3. rayzebio.com rayzebio.com/wp-content/uploads/2024/12/Mayer-SABCS-2024_RYZ101-201-TIP_Poster_Final.pdf

RYZ101 (225Ac-DOTATATE) ± pembrolizumab in estrogen ... The aims of the study are to determine the RP2D, the optimal treatment regimen, and to evaluate preliminary efficacy of RYZ101 alone and in ...

4. onclive.com onclive.com/view/mayo-clinic-treats-first-person-in-the-us-with-a-novel-radiopharmaceutical-therapy-for-breast-cancer

Mayo Clinic Treats First Person in the US With a Novel ... "The alpha emitter's potential lies in its power and in its ability to precisely kill even a single cancer cell without injuring surrounding ...

5. cancer.iu.edu cancer.iu.edu/patients/clinical-trials/61809

CTO-RYZ101-201: Clinical Trial Information Information about IUSCCC Clinical Trial CTO-RYZ101-201: Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) in subjects with estrogen receptor-positive ...