BBO-10203 + Trastuzumab for Breast Cancer

Recruiting at 10 trial locations

Overseen By 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

153 Participants Needed

Trial Summary

What is the purpose of this trial?

First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with trastuzumab in patients with advanced solid tumors.

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.

What data supports the effectiveness of the drug BBO-10203 + Trastuzumab for breast cancer?

Trastuzumab, a part of the treatment, has been shown to improve survival in patients with HER2-positive breast cancer by enhancing the effects of chemotherapy and has substantial antitumor activity on its own. It is well-tolerated and effective, with response rates between 44%-86% in combination with other drugs for metastatic breast cancer. ^{1 2 3 4 5}

Is the combination of BBO-10203 and Trastuzumab safe for humans?

Trastuzumab, also known as Herceptin and other names, has been used safely in combination with other drugs for treating HER2-positive breast cancer. It is generally well-tolerated, though some patients may experience manageable side effects like neutropenia (low white blood cell count) and rare cardiac events. ^{2 6 7 8 9}

What makes the drug BBO-10203 + Trastuzumab unique for breast cancer treatment?

The combination of BBO-10203 with trastuzumab is unique because it potentially offers a novel approach to targeting the HER2 receptor in breast cancer, which is a protein that promotes the growth of cancer cells. Trastuzumab is already known for its effectiveness in enhancing chemotherapy effects, and the addition of BBO-10203 could provide a new mechanism or enhance the existing treatment efficacy. ^{1 6 8 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Combination Dose Escalation Experimental Treatment 2 Interventions

Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) QD in combination with trastuzumab IV (8mg/kg over 90 minutes on Cycle 1 Day 1, 6mg/kg over 30-90 minutes during subsequent cycles)/SC (600mg). This cohort will enroll patients with advanced breast cancer.

Group II: Cohort 1b - BBO-10203 Combination Dose Expansion Experimental Treatment 2 Interventions

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

Group III: Cohort 1a - Monotherapy Dose Escalation/Cohort Expansion Experimental Treatment 1 Intervention

Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) once daily (QD) as monotherapy. This cohort will enroll patients with 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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Adjuvant treatment of breast cancer: impact of monoclonal antibody therapy directed against the HER2 receptor. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiac safety of (neo)adjuvant trastuzumab in the community setting: a single-center experience. [2020]

5. Greece pubmed.ncbi.nlm.nih.gov

Lapatinib-plus-pegylated liposomal doxorubicin in advanced HER2-positive breast cancer following trastuzumab: a phase II trial. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Clinical Evaluation of Dual Inhibition with Pertuzumab and Trastuzumab Biosimilar SB3 in HER2-Positive Breast Cancer Patients. [2022]

7. United States 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. [2021]

8. United States 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. [2022]

9. France 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. [2015]

10. United States 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. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Trastuzumab and Pertuzumab for Early HER2-Positive Breast Cancer: A Real World Experience. [2022]