BBI-825 for Solid Tumors

(STARMAP Trial)

No longer recruiting at 4 trial locations

Overseen By Jaye Meyer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boundless Bio

Must not be taking: CYP3A inhibitors

Disqualifiers: Hematologic malignancies, CNS malignancy, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BBI-825 for individuals with advanced solid tumors that cannot be surgically removed and have not responded to other treatments. The main goal is to assess the safety and effectiveness of BBI-825 alone and in combination with other targeted therapies. This trial suits those whose cancer has worsened despite all available treatments and who have the necessary tumor tissue samples for study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial protocol does not specify if you must stop all current medications, but you cannot use strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9, or CYP2C19. Also, you must not have taken any standard anticancer drugs within 4 weeks or 5 half-lives before the trial.

Will I have to stop taking my current medications?

The trial requires that you stop taking any approved or standard anticancer drugs or biological products at least 4 weeks before starting. Also, you cannot use strong inhibitors or inducers of certain enzymes (CYP3A, CYP2C8, CYP2C9, or CYP2C19) while participating.

Is there any evidence suggesting that BBI-825 is likely to be safe for humans?

Research shows limited safety information for BBI-825, as it is a new treatment being tested in humans for the first time. Detailed knowledge about its tolerance and potential side effects is not yet available.

In this early-stage trial, the main goal is to assess its safety. The study aims to find the safest dose that does not cause harmful effects. As the trial focuses on determining the best dose and understanding BBI-825's safety, researchers are still gathering safety data.

Prospective participants should know that the treatment is in the early stages of human testing. This means there may be more unknowns about its safety compared to treatments studied for a longer time. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BBI-825 is unique because it targets solid tumors with a novel approach. Unlike standard treatments, which often rely on chemotherapy or radiation, BBI-825 is administered orally and works by inhibiting specific pathways involved in tumor growth. This targeted mechanism may result in fewer side effects and improved outcomes for patients. Researchers are particularly excited about its potential to disrupt tumor activity more precisely and with greater efficacy than current treatments.

What evidence suggests that BBI-825 might be an effective treatment for solid tumors?

Research has shown that BBI-825, which participants in this trial will receive, holds promise for treating solid tumors. Early lab studies demonstrated that this drug blocks ribonucleotide reductase (RNR), an enzyme that aids cancer cell growth. Blocking this enzyme led to a noticeable reduction in tumor growth and even shrinkage in some cases. BBI-825 also disrupted cancer cell processes dependent on extra DNA, making survival more difficult for these cells. These early findings suggest that BBI-825 may effectively slow or halt the growth of solid tumors. ^{1 6 7 8 9}

Who Is on the Research Team?

Robert Doebele, MD

Principal Investigator

Boundless Bio

Are You a Good Fit for This Trial?

This trial is for individuals with solid tumors that have developed resistance to other treatments. Participants must have specific gene amplifications linked to this resistance. The study excludes those who don't meet the necessary health standards or might be at risk due to the treatment.

Inclusion Criteria

Availability of FFPE tumor tissue, archival or newly obtained

My liver and kidney functions are normal.

My cancer has spread, can't be surgically removed, and hasn't responded to standard treatments.

Exclusion Criteria

I have not been treated with specific RNR inhibitor drugs before.

I haven't taken any cancer drugs or biological products in the last 4 weeks.

I have or had lung inflammation that needed strong medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Single agent BBI-825 is administered orally twice daily in 28-day cycles to determine the maximum tolerated dose and recommended Phase 2 dose

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent adverse events

30 days

What Are the Treatments Tested in This Trial?

Interventions

• BBI-825

Trial Overview The trial is testing BBI-825, a new oral medication aimed at stopping tumor growth by inhibiting an enzyme called RNR. It's given alone or with other targeted therapies, and researchers are looking for the safest and most effective dose.

How Is the Trial Designed?

Group I: Single Agent Dose Escalation Experimental Treatment 1 Intervention

Single agent BBI-825, administered orally, twice daily, in 28-day cycles

Who Is Running the Clinical Trial?

Boundless Bio

Lead Sponsor

Trials

2

Recruited

190+

Published Research Related to This Trial

Icotinib hydrochloride, a selective EGFR TKI, was found to be generally well tolerated in 36 patients with advanced solid tumors, particularly non-small-cell lung cancer (NSCLC), with manageable side effects like rash and diarrhea.

The study showed promising clinical activity, with 7 out of 33 NSCLC patients achieving a partial response and 7 showing stable disease, suggesting that icotinib could be an effective treatment option after platinum-based chemotherapy failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors. Zhao, Q., Shentu, J., Xu, N., et al.[2022]

In a study of 55 patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) receiving BTK inhibitors, 7.69% of those with resolved HBV infection experienced hepatitis B virus reactivation (HBVr), indicating a moderate risk during treatment.

The overall response rate to BTK inhibitors was 70.9%, and the presence of HBV infection did not impact treatment efficacy, suggesting that while monitoring for HBVr is important, BTK inhibitors remain effective regardless of HBV status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of HBV reactivation in relapsed or refractory diffuse large B-cell lymphoma patients receiving Bruton tyrosine kinase inhibitors therapy. Ni, Y., Gao, L., Lu, Y., et al.[2022]

A study analyzing 10,320 cardiac event reports linked to Bruton tyrosine kinase inhibitors (BTKIs) found that 17.63% of these cases involved death or life-threatening events, indicating significant cardiac risks associated with these medications.

Ibrutinib was identified as having the strongest association with cardiac complications, particularly atrial fibrillation, while acalabrutinib showed a statistically lower risk compared to ibrutinib, highlighting the variability in cardiotoxicity among different BTKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance analysis of cardiac risks associated with Bruton tyrosine kinase inhibitors. Zhai, Y., Hu, F., Shi, W., et al.[2023]

Bruton's tyrosine kinase (BTK) inhibitors, already approved by the FDA, show promise as new treatments for patients with solid tumors that are resistant to traditional chemotherapy.

Emerging evidence suggests that BTK inhibitors could be combined with other therapies to create effective treatment regimens for metastatic and therapy-refractory solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Solid Tumors With BTK Inhibitors. Uckun, FM., Venkatachalam, T.[2021]

Immune checkpoint inhibitors (ICIs) have shown promising efficacy in treating triple-negative breast cancer (TNBC), particularly in patients with high PD-L1 expression, leading to improved survival rates when combined with chemotherapy.

Recent trials, such as KEYNOTE-355 and KEYNOTE-522, demonstrated that adding ICIs to standard chemotherapy not only enhances progression-free survival in metastatic TNBC but also increases pathologic complete response rates in early-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Immunotherapy in Breast Cancer. Jacob, SL., Huppert, LA., Rugo, HS.[2023]

In a study using immunocompromised mice with TCF3-PBX1 positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL), treatment with the BTK inhibitor ibrutinib did not extend the lifespan of the mice compared to those receiving a placebo, indicating limited efficacy in this context.

While ibrutinib was shown to be biologically active by reducing phospho-BTK levels, it did not improve leukemic cell viability or tumor growth, and it exhibited an antagonistic effect when combined with vincristine, suggesting it may not be the best treatment option for this specific type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib is not an effective drug in primografts of TCF3-PBX1. van de Ven, C., Boeree, A., Stalpers, F., et al.[2021]

Ibrutinib, a BTK inhibitor, effectively reduces the immunosuppressive functions of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) models, leading to increased CD8+ T cell infiltration and decreased tumor growth.

The study shows that using ibrutinib in combination with anti-PDL1 checkpoint inhibitors enhances the antitumor immune response, suggesting a promising strategy for improving immunotherapy outcomes in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTK Inhibition Reverses MDSC-Mediated Immunosuppression and Enhances Response to Anti-PDL1 Therapy in Neuroblastoma. Ishfaq, M., Pham, T., Beaman, C., et al.[2023]

Bruton's tyrosine kinase inhibitors (BTKis) are effective in treating B-cell malignancies but are associated with cardiovascular side effects, particularly an increased risk of atrial fibrillation, bleeding, and hypertension.

Newer generations of BTKis may have a lower risk of cardiovascular issues, but long-term safety data is still lacking, highlighting the need for careful management of cardiovascular risk factors in patients undergoing BTKi treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and Management of Cardiovascular Effects of Bruton's Tyrosine Kinase Inhibitors. Aghel, N., Baro Vila, RC., Lui, M., et al.[2023]

Next-generation immunotherapies (NGIO) targeting various immune checkpoints and costimulatory molecules have shown promise in early clinical trials for treating triple negative breast cancer (TNBC), demonstrating safety and early signs of antitumor activity.

To maximize the effectiveness of these therapies, patient selection based on immune biomarkers will be crucial, allowing for tailored treatment strategies that consider individual patient and tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational immunomodulatory drugs for enhancement of triple negative breast cancer (TNBC) immunotherapy: early phase development. Tarantino, P., Antonarelli, G., Ascione, L., et al.[2022]

Immune checkpoint inhibitors (ICIs) show promise for treating brain metastases in triple-negative breast cancer (TNBC), but only a small fraction (3.3%) of patients in clinical trials for ICIs had brain metastases, highlighting a significant gap in research.

There is a critical need for more inclusive clinical trials and real-world studies to evaluate the safety and efficacy of ICIs specifically for patients with breast cancer brain metastases, as current data is limited and does not adequately address this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors in the Treatment of Breast Cancer Brain Metastases. Schlam, I., Gatti-Mays, ME.[2022]

Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment for advanced triple-negative breast cancer (TNBC), particularly for patients with PD-L1-positive tumors, leading to improved clinical outcomes and long-term disease control in some cases.

In early-stage TNBC, ICI-based combination therapies show potential benefits regardless of PD-L1 expression, indicating that immunotherapy could be effective even in patients who do not typically express this marker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of immune checkpoint inhibitors in the treatment of triple-negative breast cancer. Steiner, M., Tan, AR.[2021]

Immune checkpoint inhibitors (ICIs) show promise as a treatment for a small group of patients with metastatic triple negative breast cancer (mTNBC), indicating potential for immunotherapy in this challenging cancer type.

Combination therapies involving ICIs, such as chemoimmunotherapy for PD-L1 positive patients, have demonstrated significant efficacy and are being actively researched to improve treatment outcomes for mTNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-based combinations for metastatic triple negative breast cancer in clinical trials: current knowledge and therapeutic prospects. Rizzo, A., Ricci, AD., Lanotte, L., et al.[2022]

In a study involving 122 patients with advanced solid tumors, the combination of ibrutinib and durvalumab showed an acceptable safety profile, with adverse events consistent with known effects of both drugs.

However, the antitumor activity was limited, with overall response rates of only 2% for pancreatic cancer, 3% for breast cancer, and 0% for non-small cell lung cancer, indicating that this combination may not be effective for these types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors. Hong, D., Rasco, D., Veeder, M., et al.[2021]

High expression of Bruton's tyrosine kinase (BTK) in non-small-cell lung carcinoma (NSCLC) patients is associated with poor prognosis and resistance to EGFR tyrosine kinase inhibitors (TKIs), based on analysis of surgical specimens from 80 patients.

In laboratory studies, inhibiting BTK with Acalabrutinib enhanced the effectiveness of EGFR TKIs like Gefitinib and Osimertinib, suggesting that targeting BTK could be a promising strategy to overcome TKI resistance in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bruton's tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma. Yeh, CT., Chen, TT., Satriyo, PB., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06299761

NCT06299761 | Study of the RNR Inhibitor BBI-825 in ... BBI-825 will be administered orally (PO) twice daily (BID) to subjects with locally advanced or metastatic non-resectable solid tumors, whose disease has ...

2. investors.boundlessbio.com investors.boundlessbio.com/news-releases/news-release-details/boundless-bio-announces-first-patient-dosed-first-human-phase-0

Release Details In preclinical studies, BBI-825 demonstrated low double digit nanomolar RNR inhibition and tumor growth inhibition, including regressions, in ...

3. withpower.com withpower.com/trial/phase-1-tumors-solid-2-2024-c1fb7

BBI-825 for Solid Tumors (STARMAP Trial) Trial Overview The trial is testing BBI-825, a new oral medication aimed at stopping tumor growth by inhibiting an enzyme called RNR. It's given alone or with ...

4. synapse.patsnap.com synapse.patsnap.com/drug/f9b40df9259148b48f7ecb9cdc3ad339

BBI-825 These data suggest that the combination of BBI-825 with mutant-specific, pan, and multi-RAS targeting inhibitors delayed or prevented acquired resistance in ...

5. investors.boundlessbio.com investors.boundlessbio.com/news-releases/news-release-details/boundless-bio-provides-business-updates-focused-key-value

Release Details BBI-825 was shown to dysregulate ecDNA-reliant cancer cell dNTP pools, deplete ecDNA, and was synthetic lethal in multiple oncogene ...

6. investors.boundlessbio.com investors.boundlessbio.com/news-releases/news-release-details/boundless-bio-announces-pipeline-and-leadership-updates

Boundless Bio Announces Pipeline and Leadership Updates The company has reaffirmed its expectation to report preliminary clinical proof-of-concept safety and antitumor activity data in the second half ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/boundless-bio-cancer-treatment-trial/

Boundless Bio doses first subject in advanced cancer ... Boundless Bio has dosed the first subject in the Phase I/II trial of BBI-825 for treating cancers exhibiting resistance gene amplifications.

8. ctv.veeva.com ctv.veeva.com/study/study-of-the-rnr-inhibitor-bbi-825-in-subjects-with-tumors-with-resistance-gene-amplifications

Study of the RNR Inhibitor BBI-825 in Subjects With Tumors ... BBI-825 is a potent, selective, oral, small molecule inhibitor of ribonucleotide reductase (RNR). This is a first-in-human, open-label, ...

9. aacr.org aacr.org/wp-content/uploads/2025/10/MTCT25_LBCTAbstracts_titlesONLY.pdf

Current as of October 13, 2025 Late-Breaking/Clinical Trial ... adult patients with advanced relapsed and/or refractory solid tumors. Kyri Papadopoulos. South Texas Accelerated Research Therapeutics (START), ...