DB-1303 for Breast Cancer

Recruiting at 428 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, DB-1303, for advanced breast cancer that is hormone receptor-positive (HR+) with low levels of HER2 protein. The study compares DB-1303, a potential new drug, to standard chemotherapy options to determine which more effectively prevents cancer progression. Individuals with HER2-low breast cancer that has spread and who have not responded to hormone therapy may be suitable candidates. Participants should have a tissue sample available for testing and must not have received prior chemotherapy for advanced cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to a potentially groundbreaking treatment.

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.

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

Research has shown that DB-1303 is well-tolerated by patients with advanced solid tumors. In earlier studies, patients did not experience severe side effects while using DB-1303, even those who had tried many other cancer treatments before. These findings suggest that DB-1303 might be safe for people, but ongoing studies will provide more detailed safety information.

The chemotherapy options—capecitabine, paclitaxel, and nab-paclitaxel—are FDA-approved drugs. They have been widely used to treat cancer, and their safety profiles are well-known. Common side effects include nausea, tiredness, and hair loss, but these can vary from person to person.

Overall, the treatment options in this trial have shown a reasonable safety record, but individual experiences may differ. Always consult with a healthcare professional when considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy options like capecitabine, paclitaxel, and nab-paclitaxel for breast cancer, DB-1303/BNT323 is unique because it is an experimental treatment delivered intravenously at a dosage of 8 mg/kg every three weeks. Researchers are excited about DB-1303/BNT323 because it potentially offers a new mechanism of action that could improve outcomes for patients who have not responded well to traditional chemotherapy. This novel approach targets specific pathways in cancer cells, which might result in better control of the disease with fewer side effects.

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

Research has shown that DB-1303/BNT323, one of the treatments in this trial, yields promising results in helping patients with certain types of breast cancer live longer without disease progression. In earlier studies, patients who received DB-1303 experienced better outcomes than those who underwent standard chemotherapy. This treatment targets specific proteins on cancer cells, slowing the cancer's growth. While these findings are encouraging, further research is underway to fully understand its potential. Participants in this trial may receive either DB-1303/BNT323 or an investigator's choice of single-agent chemotherapy, including capecitabine, paclitaxel, or nab-paclitaxel. ^{1 2 3 6 7}

Who Is on the Research Team?

Joyce O'Shaughnessy, PHD

Principal Investigator

Texas Oncology - Baylor Charles A. Sammons Cancer center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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 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 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]

Citations

1. investors.biontech.de investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-announce-phase-3-trial-adc-candidate

BioNTech and DualityBio Announce Phase 3 Trial of ADC ... BioNTech and DualityBio Announce Phase 3 Trial of ADC Candidate BNT323/DB-1303 Met Primary Endpoint of Progression Free Survival in HER2- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06018337

NCT06018337 | A Study of DB-1303/BNT323 vs ... The primary purpose of the study is to determine the efficacy and safety of DB-1303/BNT323 compared with investigator's choice single agent chemotherapy in the ...

3. targetedonc.com targetedonc.com/view/trastuzumab-pamirtecan-shows-efficacy-in-phase-3-for-her2-positive-breast-cancer

Trastuzumab Pamirtecan Shows Efficacy in Phase 3 for ... A groundbreaking study shows trastuzumab pamirtecan significantly improves progression-free survival in HER2-positive breast cancer patients ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3023

Safety and efficacy of DB-1303 in patients with advanced/ ... Here we report the results from dose-escalation. Results: As of Jan 13, 2023, 85 pts received DB-1303 at 6 dose levels (2.2, 4.4, 6.0, 7.0, 8.0, ...

5. en.dualitybiologics.com en.dualitybiologics.com/news/593.html

DualityBio and BioNTech Announce Phase 3 Trial of ... “The positive Phase 3 data and trastuzumab pamirtecan meeting the primary endpoint at the interim analysis indicate the potential of the BNT323/DB-1303 program ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01902-1/fulltext

436TiP DYNASTY-Breast02: A phase III trial of BNT323/DB ... A phase III trial of BNT323/DB-1303 vs investigator's choice chemotherapy in HER2-low, hormone receptor positive, metastatic breast cancer.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05150691

NCT05150691 | A Phase 1/2a Study of DB-1303/BNT323 ... This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303/BNT323 in subjects with advanced solid tumors ...