DB-1303 for Breast Cancer

Recruiting at 298 trial locations

Overseen By Michael Sun, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: DualityBio Inc.

Must not be taking: Anti-HER2, Exatecan derivatives

Disqualifiers: Uncontrolled illness, Cardiovascular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 51 months

532 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to assess the efficacy of DB-1303/BNT323 compared with investigator's choice chemotherapy in terms of progression-free survival (PFS) by blinded independent central review (BICR) in the HR+, HER2-low (immunohistochemistry \[IHC\]2+/in situ hybridization \[ISH\]- and IHC 1+) population.

Will I have to stop taking my current medications?

The trial mentions that participants must have an adequate treatment washout period before randomization, which suggests you may need to stop certain medications before joining. However, the specific medications that need to be stopped are not detailed in the provided information.

What data supports the effectiveness of the drug DB-1303 for Breast Cancer?

Research shows that nanoparticle albumin-bound paclitaxel (Abraxane) is effective in treating breast cancer, with better response rates and longer survival compared to conventional paclitaxel. This suggests that DB-1303, which includes similar components, may also be effective. ^{1 2 3 4 5}

Is DB-1303 (nab-paclitaxel) safe for humans?

Nab-paclitaxel (DB-1303) is generally considered safe for humans, as it avoids the use of toxic solvents and does not require premedication to prevent allergic reactions. Studies have shown it is well tolerated, with some patients experiencing mild to moderate sensory neuropathies (nerve-related side effects). ^{1 2 4 6 7}

How is the drug DB-1303 for breast cancer different from other treatments?

DB-1303 includes nanoparticle albumin-bound paclitaxel, which is a novel form of the drug paclitaxel that doesn't require toxic solvents, making it safer and potentially more effective by increasing the drug concentration in tumors. This formulation is associated with fewer side effects and improved outcomes compared to traditional paclitaxel treatments. ^{2 5 8 9 10}

Research Team

Lily Hu

Principal Investigator

DualityBio Inc.

Eligibility Criteria

Adults with advanced or metastatic breast cancer that is HR+, HER2-low, and have not had chemotherapy for this stage of the disease. They must be in good physical condition (ECOG 0 or 1), have a life expectancy over 12 weeks, and agree to use effective contraception. Those who've progressed on endocrine therapy plus CDK4/6 inhibitor or two lines of endocrine therapy are eligible.

Inclusion Criteria

I am fully active or can carry out light work.

I am an adult and have agreed to participate.

My breast cancer is advanced, not previously HER2-positive, but has low HER2 and is hormone receptor positive.

Exclusion Criteria

I have serious heart problems that are not well-managed.

I do not have any serious illnesses or conditions that would stop me from following the study rules.

I haven't needed treatment for fluid buildup in my chest or abdomen in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either DB-1303/BNT323 or investigator's choice chemotherapy until disease progression or other discontinuation criteria are met

Up to approximately 51 months

Every 3 weeks for DB-1303/BNT323; every 3-4 weeks for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

35 days after the last dose of study treatment

Treatment Details

Interventions

• Capecitabine
• DB-1303
• Nab-paclitaxel
• Paclitaxel

Trial Overview The trial tests DB-1303 against standard chemotherapies like Paclitaxel, Nab-paclitaxel, Capecitabine chosen by the investigator. It measures how long patients live without their cancer getting worse using blinded independent review.

Participant Groups

Group I: DB-1303/BNT323 Experimental Treatment 1 Intervention

Enrolled Subjects will be randomized to receive a 8 mg/kg IV dose of DB-1303/BNT323 on Day 1 of each cycle Q3W

Group II: investigator's choice single agent chemotherapy Active Control 3 Interventions

Enrolled Subjects will be randomized to receive investigator's choice single agent chemotherapy (capecitabine:1000 or 1250 mg/m2, Oral, Twice daily orally for 2 weeks followed by a 1-week rest period in 3-week cycles; paclitaxel：80 mg/m2， IV, Every week (QW) in 3-week cycles; or nab-paclitaxel: 100 mg/m2, IV, Every week (QW) for 3 weeks followed by a one-week rest period in 4-week cycles) until RECIST 1.1 defined disease progression (PD), unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

DualityBio Inc.

Lead Sponsor

Trials

12

Recruited

5,800+

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

ABI-007, a novel albumin-bound formulation of paclitaxel, has shown superior efficacy compared to standard paclitaxel while significantly reducing toxicity in a large phase III trial.

This new formulation is solvent-free and enhances the circulation time of the drug, providing oncologists with more effective treatment options for metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. Miele, E., Spinelli, GP., Miele, E., et al.[2022]

ABI-007, a novel formulation of paclitaxel, can be safely administered at higher doses than traditional paclitaxel formulations, with maximum-tolerated doses of 100 mg/m² for heavily pretreated patients and 150 mg/m² for lightly pretreated patients.

The study showed partial antitumor responses in patients with breast, lung, and ovarian cancers, indicating that ABI-007 may be effective even in those previously treated with standard paclitaxel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. Nyman, DW., Campbell, KJ., Hersh, E., et al.[2022]

In a study of 81 women with early-stage estrogen receptor-positive breast cancer, nab-Paclitaxel showed significant antitumor activity with a good response rate (RCB 0+I) of 24.7%, indicating its effectiveness as a neoadjuvant treatment despite a higher than expected poor response rate (RCB III) of 28.4%.

The treatment was associated with low rates of severe toxicity, with neutropenia being the most common side effect, and an exploratory analysis suggested that overexpression of the SPARC protein in tumors may predict a complete response, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. Martín, M., Chacón, JI., Antón, A., et al.[2021]

Nab-PTX (Abraxane®) was administered to 31 breast cancer patients without any allergic reactions, indicating it is well tolerated, even in those with alcohol intolerance.

Among patients with locally advanced operable breast cancer, higher doses (260 mg/m²) resulted in a better response rate, with 10 out of 13 showing a partial response, suggesting its efficacy in treating advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of nab-Paclitaxel treatment in 31 patients with breast cancer]. Tauchi, Y., Kashiwagi, S., Ishihara, S., et al.[2015]

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

In a study of 42 metastatic breast cancer patients who had previously been treated with taxanes, nab-paclitaxel demonstrated a 23.8% overall response rate, indicating significant antitumor activity despite prior treatment failures.

Nab-paclitaxel was well tolerated, with most treatment-related side effects being mild to moderate, suggesting a manageable safety profile for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients. Fabi, A., Giannarelli, D., Malaguti, P., et al.[2022]

In a study involving 152 patients with HER2- early-stage breast cancer, weekly nab-paclitaxel showed comparable efficacy to docetaxel in achieving pathologic complete response (pCR) rates, with 12% for docetaxel and 17% for nab-paclitaxel, indicating it is a viable alternative for neoadjuvant chemotherapy.

Nab-paclitaxel was associated with a similar incidence of severe adverse events compared to docetaxel, but notably, it did not cause any grade 3/4 peripheral sensory neuropathy, suggesting a better safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Multicenter Phase II Trial of Neoadjuvant Therapy Comparing Weekly Nab-paclitaxel Followed by FEC With Docetaxel Followed by FEC in HER2- Early-stage Breast Cancer. Kuwayama, T., Nakamura, S., Hayashi, N., et al.[2022]

In a phase II clinical trial involving 55 patients with operable breast cancer, preoperative chemotherapy using nanoparticle albumin-bound paclitaxel (nab-PTX) followed by an epirubicin and cyclophosphamide regimen achieved a pathological complete response (pCR) rate of 22.2%, indicating its efficacy in treating this condition.

The study found that HER2-positive patients had a significantly higher pCR rate of 60%, suggesting that HER2 status is an important factor in predicting treatment response, while the overall safety profile of the treatment was considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. Futamura, M., Nagao, Y., Ishihara, K., et al.[2018]

References

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

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

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

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. [2022]

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

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical experience of nab-Paclitaxel treatment in 31 patients with breast cancer]. [2015]

7. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients. [2022]

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

Randomized Multicenter Phase II Trial of Neoadjuvant Therapy Comparing Weekly Nab-paclitaxel Followed by FEC With Docetaxel Followed by FEC in HER2- Early-stage Breast Cancer. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. [2018]