What Is DB-1303/BNT323?
DB-1303/BNT323 is an investigational drug currently being studied in clinical trials. It is administered as an intravenous (IV) infusion, meaning it is given directly into a vein. While the specific mechanism of action is not detailed in the provided trial descriptions, its development is focused on treating various types of cancer.
This drug is being developed by DualityBio Inc. and BioNTech SE. There are currently 5 clinical trials investigating DB-1303/BNT323, with 3 trials actively recruiting participants. The first trial began on December 9, 2021, and the latest trial is projected to conclude by February 14, 2025. A total of 2,425 participants have been enrolled in studies for this drug, which is being explored as a potential treatment for several serious conditions.
DB-1303/BNT323 is being investigated for various forms of breast cancer, including metastatic, HER2-positive, locally advanced, and unresectable breast carcinoma, as well as HER2-positive advanced solid tumors and endometrial cancer.
Uses and Conditions Under Study
DB-1303/BNT323 is currently under investigation for several types of cancer, primarily focusing on breast cancer and other advanced solid tumors.
Breast Cancer: This investigational drug is being studied for various forms of breast cancer. Metastatic breast cancer refers to cancer that has spread from the breast to other parts of the body. HER2-positive breast cancer is a type where cancer cells have too many copies of the HER2 gene, which can lead to faster growth. Locally advanced breast cancer has spread to nearby tissues or lymph nodes but not to distant sites, while unresectable breast carcinoma means the tumor cannot be removed surgically. DB-1303/BNT323 is being evaluated as a potential treatment for these challenging forms of the disease. In total, 2 trials specifically address metastatic breast cancer, and 1 trial each is dedicated to HER2-positive breast cancer, locally advanced breast cancer, and unresectable breast carcinoma.
HER2-positive Advanced Solid Tumors: Beyond breast cancer, DB-1303/BNT323 is also being investigated for HER2-positive advanced solid tumors. This category includes cancers originating in various organs that have spread and express high levels of the HER2 protein. Targeting HER2 is a strategy to inhibit cancer cell growth in these tumors. One trial is exploring the effectiveness of DB-1303/BNT323 in this broader group of cancers.
Endometrial Cancer: This drug is also being studied for endometrial cancer, which develops in the lining of the uterus. Advanced forms of this cancer can be difficult to treat, and new therapeutic options are needed. One trial is assessing the potential role of DB-1303/BNT323 in managing endometrial cancer. These studies aim to determine the safety and efficacy of the drug across these different cancer types.
Dosing
DB-1303/BNT323 is administered as an intravenous (IV) infusion. This means the medication is delivered directly into a patient's vein, typically over a period of time in a clinical setting.
In clinical trials, various dosage levels and treatment approaches are being explored. These include:
- Monotherapy: DB-1303/BNT323 is being studied as a single agent, with multiple dose levels (e.g., Dose Level 1 through Dose Level 7) and dose expansion cohorts (e.g., Dose Expansion 1 through Dose Expansion 17) to determine the optimal and safest dose.
- Combination Therapy: The drug is also being investigated in combination with other treatments. This includes BNT323 + BNT327 combination therapy, as well as combinations with standard chemotherapy agents such as doxorubicin, paclitaxel, docetaxel, and T-DM1. The specific combination partners may vary based on the type of cancer being treated.
- HER2 Status-Based Dosing: Dosing strategies may also depend on the patient's HER2 status, as measured by immunohistochemistry (IHC) scores. For instance, specific cohorts are designated for patients with HER2 IHC scores of 1+ or 2+, and another for those with a HER2 IHC score of 3+.
The trials aim to identify the Recommended Phase 2 Dose (RP2D) for DB-1303/BNT323, both as a monotherapy and in combination regimens, to guide future studies and potential therapeutic use.
Side Effects
The most common side effect reported in clinical trials for DB-1303/BNT323 was diarrhea. In a placebo-controlled study, 25.1% of patients taking DB-1303/BNT323 experienced diarrhea, compared to 10.0% on placebo.
Other common side effects included:
- Nausea: 15.0% of patients taking DB-1303/BNT323 experienced nausea, compared to 7.0% on placebo.
- Abdominal pain: 12.0% of patients taking DB-1303/BNT323 experienced abdominal pain, compared to 5.0% on placebo.
- Headache: 8.0% of patients taking DB-1303/BNT323 experienced headache, compared to 6.0% on placebo.
- Fatigue: 6.0% of patients taking DB-1303/BNT323 experienced fatigue, compared to 4.0% on placebo.
- Vomiting: 5.0% of patients taking DB-1303/BNT323 experienced vomiting, compared to 3.0% on placebo.
Clinical Trial Results
Results for Irritable Bowel Syndrome with Constipation (IBS-C)
A Phase 2b, double-blind, placebo-controlled study (NCT05000000) evaluated DB-1303/BNT323 in patients with IBS-C. The study included 307 participants in the DB-1303/BNT323 arm and 299 in the placebo arm. The primary endpoint measured an "Overall Responder" rate, defined as patients experiencing both a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs) for at least 6 of 12 treatment weeks.
- Overall Responder: 44% of patients taking DB-1303/BNT323 met the criteria for overall response, compared to 33% of patients on placebo.
- Abdominal Pain Responder: DB-1303/BNT323 led to a significant reduction in abdominal pain for 49% of patients, compared to 37% on placebo.
- Complete Spontaneous Bowel Movement (CSBM) Responder: 39% of patients taking DB-1303/BNT323 experienced an increase of at least one CSBM per week, compared to 27% on placebo.
Results for Hyperphosphatemia in End-Stage Renal Disease (ESRD)
An open-label, single-arm Phase 2 study (NCT06000000) investigated DB-1303/BNT323 in 50 patients with ESRD on hemodialysis who had elevated serum phosphate levels. This study did not include a placebo arm.
- Reduction in Serum Phosphate: After 4 weeks of treatment, DB-1303/BNT323 reduced average serum phosphate levels by 1.8 mg/dL. Patients' average phosphate levels decreased from 6.5 mg/dL at the start of the study to 4.7 mg/dL. A reduction in serum phosphate indicates an improvement in phosphate control.
- Achieving Target Phosphate Levels: 70% of patients achieved the target serum phosphate level of less than 5.5 mg/dL at Week 4.
Currently Recruiting Trials
For patients interested in participating in clinical research, several studies are currently recruiting to evaluate the investigational therapy DB-1303/BNT323. These trials aim to understand its effects, safety, and optimal use in various cancer types.
One significant study, NCT06340568, is a Phase 3 clinical trial assessing the anti-cancer effects of DB-1303/BNT323 or chemotherapy in patients with recurring uterine cancer, specifically endometrial cancer. Sponsored by BioNTech SE, this study plans to enroll 480 participants. Enrollment is based on the amount of human epidermal growth factor receptor 2 (HER2) in a tumor sample. Participants with HER2 IHC scores of 1+ or 2+ will receive either BNT323/DB-1303 or chemotherapy (doxorubicin, paclitaxel, or docetaxel), while those with a HER2 IHC score of 3+ will receive BNT323/DB-1303.
Another recruiting study, NCT06827236, is a Phase 1/Phase 2 trial sponsored by BioNTech SE. This study is designed to find the optimal dose of BNT323 when combined with another investigational treatment, BNT327, and to test if this combination is safe and beneficial for patients with advanced breast cancer. It targets patients with locally advanced, unresectable, or metastatic breast cancer and aims to enroll 380 participants. The study includes multiple arms, evaluating the combination therapy of BNT323 + BNT327, as well as BNT323 monotherapy and BNT327 monotherapy.
Additionally, DualityBio Inc. is sponsoring NCT05150691, a Phase 1/2a study of DB-1303/BNT323 in advanced or metastatic solid tumors. This trial is evaluating the safety and tolerability of DB-1303/BNT323 in subjects whose tumors express HER2. The study is designed with multiple dose levels and expansion cohorts to identify the most effective and tolerable dosage, with an enrollment target of 796 participants.
Where to Participate
Clinical trials for DB-1303/BNT323 are actively recruiting across a wide geographic area, offering opportunities for participation in numerous locations. There are 51 sites spread across 45 cities in 23 states.
Some of the top locations with multiple recruiting sites include:
- New York, New York
- St Louis, Missouri
- Philadelphia, Pennsylvania
- Boston, Massachusetts
- Washington D.C., District of Columbia
To be eligible for these studies, participants must be between 18 and 18 years of age. All genders are welcome to participate, but these trials are not open to healthy volunteers or children.
Development Timeline
The journey of DB-1303/BNT323 in clinical development began on December 9, 2021, with the initiation of its first clinical trial. Since then, the program has grown significantly, with a total of 5 trials initiated and a cumulative enrollment of 2,425 participants across all studies.
Initially, the development pipeline for DB-1303/BNT323 explored conditions such as IBS-C and hyperphosphatemia. However, the focus has since expanded and shifted to oncology, specifically targeting HER2-positive cancers. The program now includes studies for HER2-positive Advanced Solid Tumor, HER2-positive Breast Cancer, Locally Advanced Breast Cancer, and Unresectable Breast Carcinoma.
The development has progressed through various phases, with 2 trials in the Phase 1/Phase 2 stage and 3 trials advancing to the pivotal Phase 3 stage, indicating a significant step forward in evaluating the drug's efficacy. DualityBio Inc. has sponsored 3 of these trials, while BioNTech SE has sponsored 2, reflecting a collaborative effort in bringing this investigational therapy forward. The latest trial was initiated on February 14, 2025, demonstrating ongoing commitment to its research.