BBO-10203 + Trastuzumab for Breast Cancer

Recruiting at 17 trial locations

Overseen By BBOT (BridgeBio Oncology Therapeutics)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

Must be taking: Anti-HER2 therapy

Disqualifiers: Untreated brain metastases, BRAFV600E, others

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

Compensation: Varies

Number of Visits: Unknown

392 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BBO-10203, either alone or with other cancer drugs like Trastuzumab, to assess its safety and tolerability in individuals with advanced solid tumors such as breast, colorectal, and lung cancer. The trial aims to determine the appropriate dose and understand how the body processes the drug. Suitable candidates include those with advanced breast cancer that is HER2-positive or hormone receptor-positive, advanced colorectal cancer with a specific KRAS mutation, or advanced lung cancer with the same KRAS mutation. Participants should have previously tried other treatments but require another option. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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 team or your doctor.

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

Previous studies have examined the safety and tolerability of BBO-10203. As a new treatment, researchers are still determining how well people can handle it. Specific information on side effects is not yet available because the treatment remains in early testing stages, with a primary focus on safety.

BBO-10203 is also being tested with other drugs, such as trastuzumab, fulvestrant, ribociclib, and FOLFOX with bevacizumab. Trastuzumab, for instance, is already known to be safe when combined with other cancer treatments for HER2-positive breast cancer. However, testing BBO-10203 with these drugs is part of ongoing research due to its novelty.

Overall, the safety of BBO-10203 is still under study, and the trial is in early stages, focusing on the drug's effects in the body. Prospective participants should understand that this trial is exploratory. Consulting a healthcare provider is crucial to learn about potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BBO-10203 for advanced breast cancer because it offers a new way to target cancer cells. Unlike the standard treatments like chemotherapy and hormone therapies, BBO-10203 is designed to work in combination with drugs like trastuzumab or fulvestrant, potentially enhancing their effects. One of its promising features is its oral administration, which could make it more convenient for patients compared to intravenous treatments. Additionally, its combination with other targeted therapies, such as ribociclib, aims to tackle cancer more effectively by hitting multiple pathways that cancer cells use to grow. This multi-faceted approach could lead to better outcomes for patients with specific types of advanced breast cancer.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that BBO-10203 is a new drug that breaks down certain proteins aiding cancer cell growth. Early studies found that BBO-10203 can slow tumor growth in various cancers, including breast and colorectal cancer.

In this trial, participants will join different treatment arms to assess BBO-10203's effectiveness in various combinations. One arm will test BBO-10203 as a monotherapy. Another will combine BBO-10203 with trastuzumab, a drug effective against HER2-positive breast cancer, where BBO-10203 has shown strong effects against tumors. Other arms will explore combining BBO-10203 with treatments like fulvestrant and ribociclib for breast cancer, and with FOLFOX and bevacizumab for colorectal cancer with a specific mutation. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors: HER2-positive breast cancer, HR-positive/HER2-negative breast cancer, KRAS mutant colorectal or non-small cell lung cancer. Participants must have tried all standard treatments without success or be unsuitable for them due to tolerance issues. They should be relatively healthy (ECOG 0-1) and have a good heart function.

Inclusion Criteria

My cancer can be measured using standard imaging tests.

I have had at least 2 treatments for HER2-positive advanced breast cancer.

My heart's pumping ability is within a healthy range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BBO-10203 tablets orally once daily at different dose levels to evaluate safety and tolerability

8-12 weeks

Weekly visits (in-person)

Dose Expansion

Participants receive BBO-10203 tablets orally once daily, with or without trastuzumab, to further evaluate safety and preliminary antitumor activity

12-16 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BBO-10203
• Trastuzumab

Trial Overview The BREAKER-101 study tests BBO-10203 alone and combined with trastuzumab in patients with advanced solid tumors. It's the first time this drug is being tested in humans to see how safe it is, how well it's tolerated, and what happens to it inside the body.

How Is the Trial Designed?

Group I: BBO10203 + Fulvestrant + Ribociclib Experimental Treatment 3 Interventions

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant (500mg IM) and ribociclib (600mg orally) as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.

Group II: BBO10203 + FOLFOX + Bevacizumab Experimental Treatment 3 Interventions

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2 + 2400 mg/m2) and bevacizumab (5 mg/kg IV). This cohort will enroll patients with KRAS-mutant advanced colorectal cancer.

Group III: BBO-10203 + Trastuzumab Experimental Treatment 2 Interventions

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab (8mg/kg infusion over 90 minutes on Cycle 1 Day 1, 6mg/kg infusion over 30-90 minutes during subsequent cycles or 600mg subcutaneous). This cohort will enroll patients with HER2-positive advanced breast cancer.

Group IV: BBO-10203 + Fulvestrant Experimental Treatment 3 Interventions

Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant (500mg IM). This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer.

Group V: BBO-10203 Experimental Treatment 1 Intervention

Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) once daily as monotherapy. This cohort will enroll patients with HER2-positive advanced breast cancer, HR-positive HER2-negative advanced breast cancer, advanced colorectal cancer, and advanced lung cancer.

Who Is Running the Clinical Trial?

TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

Lead Sponsor

Trials

2

Recruited

400+

TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics)

Lead Sponsor

Published Research Related to This Trial

In a study of 117 women with HER2-positive metastatic breast cancer, the trastuzumab biosimilar SB3 combined with pertuzumab showed a median progression-free survival (PFS) of 12.7 months, indicating effective treatment outcomes.

At 12 months, the overall survival (OS) rate was 84%, suggesting that SB3 is a viable first-line therapy option comparable to the reference trastuzumab in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Treatment of HER2-Positive Metastatic Breast Cancer With Dual Blockade Including Biosimilar Trastuzumab (SB3): Population-Based Real-World Data From the DBCG. Celik, A., Berg, T., Nielsen, LB., et al.[2022]

The trastuzumab biosimilar SB3 combined with pertuzumab was found to have a safety profile similar to the original trastuzumab and pertuzumab combination, with only 5.7% of patients experiencing a significant decline in heart function (LVEF).

In the neoadjuvant setting, 50% of patients achieved a pathological complete response, indicating that SB3 plus pertuzumab is effective in treating HER2-positive breast cancer, comparable to existing treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Evaluation of Dual Inhibition with Pertuzumab and Trastuzumab Biosimilar SB3 in HER2-Positive Breast Cancer Patients. Suppan, C., Steiner, D., Klocker, EV., et al.[2022]

In a study of 78 HER2-positive breast cancer patients treated with neoadjuvant chemotherapy combined with trastuzumab and pertuzumab, a pathological complete response (pCR) rate of 46.3% was achieved, indicating effective treatment outcomes in a real-world setting.

While no cardiac toxicity was reported, diarrhea was a common side effect, affecting 74% of patients, highlighting the need for monitoring and management of gastrointestinal side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience. Hall, BJ., Bhojwani, AA., Wong, H., et al.[2022]

Trastuzumab, a humanized monoclonal antibody targeting the HER2 receptor, has shown significant effectiveness as a single-agent treatment for metastatic breast cancer and enhances the effects of chemotherapy.

Recent studies indicate that trastuzumab is also beneficial in the adjuvant setting for early-stage breast cancer, contributing to improved disease-free and overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant treatment of breast cancer: impact of monoclonal antibody therapy directed against the HER2 receptor. Simonds, HM., Miles, D.[2019]

BAT8001, a novel antibody-drug conjugate targeting HER2-positive breast cancer, showed a favorable safety profile with a maximum tolerated dose of 3.6 mg/kg, and significant adverse events were observed in 48.3% of patients, primarily thrombocytopenia.

In a study of 29 patients, BAT8001 demonstrated promising anti-tumor activity, with 41.4% achieving an objective response and 82.8% showing disease control, indicating its potential as a new treatment option for metastatic HER2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study. Hong, R., Xia, W., Wang, L., et al.[2021]

In a study of 234 HER2-positive breast cancer patients, those who received neoadjuvant trastuzumab therapy showed a significantly higher pathologic complete response (pCR) rate of 30.4% compared to 14.8% in those who did not receive the treatment, indicating its efficacy in improving initial treatment outcomes.

Patients who achieved pCR also experienced longer disease-free survival (DFS), and even those who did not achieve pCR had improved DFS when treated with trastuzumab, highlighting its role as an important predictor of better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Neoadjuvant Chemotherapy with Epirubicin and Cyclophosphamide and Weekly Paclitaxel and Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Carcinoma: A Real-World Study. Zhang, M., Li, L., Zhang, S., et al.[2022]

In a study of 17 patients with advanced HER2/neu overexpressing breast cancer, the combination of trastuzumab and paclitaxel resulted in a response rate of 59%, with 2 complete responses and a median overall survival of 23 months.

The treatment was generally well-tolerated, with manageable side effects; however, some patients experienced significant toxicities, including hypersensitivity reactions and grade 3 neuropathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4-years results of weekly trastuzumab and paclitaxel in the treatment of women with HER2/neu overexpressing advanced breast cancer: single institution prospective study. Janku, F., Pribylova, O., Zimovjanova, M., et al.[2015]

The combination of trastuzumab and vinorelbine has shown high objective response rates of 44%-86% in treating HER2-positive metastatic breast cancer, with first-line treatment rates reaching 51%-86%.

This treatment is well tolerated, with manageable side effects, including short-duration grade 3/4 neutropenia in about 50% of patients and infrequent serious cardiac events, making it suitable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the use of trastuzumab (Herceptin) plus vinorelbine in metastatic breast cancer. Chan, A.[2020]

In a study of 24 patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab, the combination of lapatinib and pegylated liposomal doxorubicin (PLD) showed a 54% overall response rate, indicating significant efficacy.

The treatment demonstrated a median progression-free survival of 5.8 months and a median overall survival of 23.3 months, making it a promising option for patients at risk of cardiotoxicity or those with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lapatinib-plus-pegylated liposomal doxorubicin in advanced HER2-positive breast cancer following trastuzumab: a phase II trial. Pircher, M., Mlineritsch, B., Fridrik, MA., et al.[2018]

In a study of 237 patients with HER2-positive breast cancer treated with trastuzumab, 20.2% experienced cardiotoxicity, which is slightly higher than rates seen in clinical trials, but most patients (96.2%) were asymptomatic.

Despite the incidence of cardiotoxicity, 41.6% of patients recovered their cardiac function, suggesting that while monitoring for heart issues is important, the benefits of trastuzumab in improving survival still outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac safety of (neo)adjuvant trastuzumab in the community setting: a single-center experience. da Fonseca, LG., de Melo Gagliato, D., Takahashi, TK., et al.[2020]

Trastuzumab (Herceptin) is a humanized monoclonal antibody that effectively targets the HER2/neu receptor, showing significant antitumor activity in patients with HER2/neu-amplified metastatic breast cancer based on multiple clinical trials.

When used in combination with chemotherapy, trastuzumab enhances treatment outcomes, improving time to progression, response rates, and overall survival, marking it as a pioneering example of targeted therapy in breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. Hortobagyi, GN.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06625775

NCT06625775 | Open-Label Study of BBO-10203 in ... This is an open-label, multi-center Phase 1a/1b study designed to evaluate the safety, tolerability, preliminary antitumor activity, and PK of BBO-10203.

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/537728

Open-Label Study of BBO-10203 in Subjects With ... First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, ...

3. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=23499&isClinicalTrial=True

ANZCTR - Registration This cohort will enroll patients with KRAS-mutant advanced colorectal cancer. Treatment: Drugs: BBO-10203. Participants will receive assigned ...

4. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/colorectal-cancer

UCLA Colorectal Cancer Clinical Trials for 2025 — Los Angeles First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination ...

5. ichgcp.net ichgcp.net/clinical-trials-registry/NCT06625775

Open-Label Study of BBO-10203 in Subjects With Advanced ... This is an open-label, multi-center Phase 1a/1b study designed to evaluate the safety, tolerability, preliminary antitumor activity, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482239/

Precise regulation of RAS-Mediated PI3Kα activation Furthermore, BBO-10203 demonstrated promising therapeutic benefits in combination with novel RAS inhibitors (e.g., BBO-8520 and BBO-11818) in ...

7. moffitt.org moffitt.org/clinical-trials-and-studies/clinical-trial-23585/

Clinical Trial 23585 Study Title: A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects with Advanced Solid ...