BNT323 + BNT327 for Breast Cancer

Recruiting at 14 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must not be taking: Topoisomerase inhibitors, PD-L1/VEGF, Immunostimulatory agents, Systemic corticosteroids

Disqualifiers: Small bowel obstruction, Uncontrolled illness, ILD/pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

380 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, BNT323 and BNT327, to evaluate their effectiveness and safety for individuals with specific types of breast cancer. It includes those with hormone receptor-positive or negative, HER2-positive, low, ultralow, or null breast cancer, as well as triple-negative breast cancer. Participants should have breast cancer that has spread or cannot be surgically removed and must have a documented history of HER2 expression. The trial aims to determine the optimal dose and understand each treatment's role in combating cancer. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial does not clearly specify if you need to stop taking your current medications. However, you cannot participate if you've recently taken certain immunosuppressive therapies or systemic corticosteroids above a specific dose. It's best to discuss your current medications with the trial team.

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

Previous studies have shown that BNT323 is well-tolerated by patients with advanced solid tumors, meaning it didn't cause severe side effects. Researchers found it showed promising results. Studies have also shown that BNT327 can be effective in treating certain types of breast cancer and is generally safe when used with other drugs. While some typical side effects like tiredness and nausea have been reported, no serious safety issues have emerged. As this trial is in its early stages, the main goal is to find the best dose and ensure safety. More information on safety will become available as the study progresses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT323 and BNT327 for breast cancer because they offer a new approach compared to standard treatments like chemotherapy, hormone therapy, or targeted drugs such as trastuzumab. BNT323 and BNT327 are unique because they work in combination to potentially enhance the body's immune response against cancer cells, a method known as immunotherapy. This combination therapy might provide a more targeted attack on cancer cells with potentially fewer side effects than traditional treatments. Additionally, the ability to fine-tune the dosage levels of these treatments could lead to more personalized and effective care for patients.

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

This trial will explore the potential of BNT323 and BNT327 in treating breast cancer. Research has shown that combining BNT323 and BNT327 may be promising. In previous studies, BNT327 demonstrated a strong response rate of 85.4% when combined with chemotherapy for small cell lung cancer, suggesting potential effectiveness for breast cancer as well. Meanwhile, BNT323 has helped patients with HER2-positive breast cancer live longer without disease progression. This trial includes arms studying BNT323 and BNT327 both as monotherapies and in combination, targeting specific cancer pathways to improve treatment outcomes. Although still in early stages, these initial findings offer hope for effectiveness in different types of breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Are You a Good Fit for This Trial?

This trial is for patients with advanced breast cancer, regardless of hormone receptor status. Participants must have confirmed HER2 status and measurable disease as per specific guidelines. They need a healthy heart function (ejection fraction ≥50%). It's not suitable for those who don't meet these criteria.

Inclusion Criteria

My breast cancer is confirmed and has spread beyond the breast.

Participants must have measurable disease defined by RECIST 1.1

My breast cancer's HER2 status is confirmed by a lab.

Exclusion Criteria

I haven't been hospitalized for a small bowel obstruction in the last 3 months.

I don't have any severe illnesses that would stop me from following the study plan.

I don't have uncontrolled fluid buildup needing treatment in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BNT323 in combination with BNT327 in a dose escalation design to define the recommended Phase 2 dose (RP2D)

21 days

Multiple visits for dose escalation and monitoring

Dose Optimization and Exploratory Cohorts

Evaluation of the efficacy and safety of the optimal dose combination in three cohorts

Up to 54 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last IMP dose

What Are the Treatments Tested in This Trial?

Interventions

• BNT323
• BNT327

Trial Overview The study tests the combination of two investigational drugs, BNT323 and BNT327, to find the best dose and assess their safety in treating advanced breast cancer. The trial will determine how well this drug combo works in different subgroups of breast cancer.

How Is the Trial Designed?

Group I: Part1 - BNT323 + BNT327 combination therapy Experimental Treatment 2 Interventions

Escalating dose levels (DLs) of BNT323 and BNT327 to define RP2D. Six DLs are planned, i.e., DL0-1, DL1-1, DL2-1, DL0-0, DL1-0, DL2-0, a combination of three different DLs for BNT323 (DL0, DL1, and DL2) and two DLs for BNT327 (DL0 and DL1).

Group II: Part 2 Cohort 4 - Selected dose level of BNT323 + BNT327 Experimental Treatment 2 Interventions

Group III: Part 2 Cohort 3 - Selected dose level of BNT323 + BNT327 Experimental Treatment 2 Interventions

Group IV: Part 2 Cohort 2 - Selected dose level of BNT323 + BNT327 Experimental Treatment 2 Interventions

Group V: Part 2 Cohort 1 - RP2D of BNT323 + BNT327 Experimental Treatment 2 Interventions

Group VI: Part 2 Cohort 1 - Lower dose or RP2D of BNT323 + BNT327 Experimental Treatment 2 Interventions

Group VII: Part 2 Cohort 1 - BNT327 monotherapy Experimental Treatment 1 Intervention

BNT327 monotherapy at a fixed dose

Group VIII: Part 2 Cohort 1 - BNT323 monotherapy Experimental Treatment 1 Intervention

BNT323 monotherapy at a fixed dose

Who Is Running the Clinical Trial?

BioNTech SE

Lead 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

DualityBio Inc.

Industry Sponsor

Trials

12

Recruited

5,800+

Biotheus Inc.

Industry Sponsor

Trials

21

Recruited

5,100+

BioNTech (Shanghai) Pharmaceuticals Co., Ltd.

Collaborator

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 ... “The positive Phase 3 data and trastuzumab pamirtecan meeting the primary endpoint at the interim analysis indicate the potential of the BNT323/ ...

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. onclive.com onclive.com/view/fda-grants-breakthrough-therapy-designation-to-bnt323-db-1303-in-endometrial-cancer

FDA Grants Breakthrough Therapy Designation to BNT323 ... The median duration of treatment was 2.6 months (range, 0.7-10.4), and 90.6% of patients remained on treatment at the data cutoff. Patients had ...

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/ ...

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. cancernetwork.com cancernetwork.com/view/trastuzumab-pamirtecan-improves-pfs-in-her2-metastatic-breast-cancer

Trastuzumab Pamirtecan Improves PFS in HER2+ ... Trastuzumab pamirtecan (BNT323/DB-1303) displayed enhanced progression-free survival (PFS) vs ado-trastuzumab emtansine (T-DM1; Kadcyla) in ...

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

Safety and efficacy of DB-1303 in patients with advanced/ ... DB-1303 was well tolerated with encouraging preliminary antitumor activity in heavily pretreated pts with advanced/metastatic solid tumors.