DB-1303 for Solid Cancers

Recruiting at 81 trial locations

Overseen By Britney Winterberger

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: DualityBio Inc.

Disqualifiers: Heart failure, Myocardial infarction, Lung diseases, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

766 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new treatment called DB-1303 (also known as BNT323) for individuals with advanced solid tumors that test positive for HER2, a protein that can affect cancer growth. Participants will receive different doses to determine the best and safest amount. The trial seeks individuals with a HER2-positive tumor that has not responded well to standard treatments or for which no standard treatment is available. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that DB-1303/BNT323 is likely to be safe for humans?

Research shows that DB-1303/BNT323 has been well-tolerated by patients with advanced solid tumors. Studies indicate that the treatment's safety profile is manageable, with side effects usually mild and controllable. Patients in previous trials reported positive results, as the treatment showed potential benefits against tumors. Overall, evidence suggests that DB-1303/BNT323 is generally safe for humans, with no major safety concerns identified so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for solid cancers?

Researchers are excited about DB-1303 because it targets solid cancers in a unique way. Unlike traditional chemotherapy, which often attacks both healthy and cancerous cells, DB-1303 is designed to specifically target cancer cells, potentially reducing side effects. This treatment involves an innovative approach: it combines DB-1303 with BNT323, aiming to enhance the therapeutic effects and improve patient outcomes. Additionally, the diverse dosing levels and expansion phases allow flexibility in finding the optimal balance between effectiveness and safety, setting it apart from current standard treatments.

What evidence suggests that this trial's treatment DB-1303 could be effective for solid cancers?

Research has shown that DB-1303, administered at different dose levels in this trial, yields promising results for treating advanced solid tumors with the HER2 protein, often linked to cancer growth. Studies have found that DB-1303 can shrink tumors and is well-tolerated, even in patients who have tried many other treatments. Early findings suggest that the drug works against various types of cancer, not just those with high HER2 levels. The FDA has granted this treatment a Breakthrough Therapy Designation, highlighting its potential to significantly help patients. These results make DB-1303 a hopeful option for those with advanced cancers. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that are HER2-positive or express HER2, and have not responded to standard treatments or have no standard options left. Participants must be relatively healthy (ECOG 0-1), have a life expectancy of at least 3 months, a functioning heart (LVEF ≥ 50%), and adequate organ function.

Inclusion Criteria

Provide signed informed consent

My cancer is HER2-positive or expresses HER2, is advanced, and doesn't respond to standard treatments.

I can provide a HER2 status report or a sample of my tumor.

Exclusion Criteria

I have a history of serious heart failure or heart rhythm problems needing treatment.

I haven't had a heart attack or unstable chest pain in the last 6 months.

I don't have lasting side effects from cancer treatment worse than mild.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of DB-1303/BNT323 to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)

21 days per cycle

1 visit per cycle (in-person)

Dose Expansion

Participants receive the RP2D to confirm safety, tolerability, and explore efficacy in selected malignant solid tumors

21 days per cycle

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

35 days post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• DB-1303

Trial Overview The study tests DB-1303's safety and effectiveness in different doses for those with specific types of advanced cancer. It includes other drugs like Itraconazole, Pertuzumab Injection, Ritonavir as part of the treatment regimen in a Phase 1/2a setting.

How Is the Trial Designed?

Group I: DB-1303/BNT323 Dose Level 7 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 7 on Day 1 of each cycle Q3W

Group II: DB-1303/BNT323 Dose Level 6 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 6 on Day 1 of each cycle Q3W

Group III: DB-1303/BNT323 Dose Level 5 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 5 on Day 1 of each cycle Q3W

Group IV: DB-1303/BNT323 Dose Level 4 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 4 on Day 1 of each cycle Q3W

Group V: DB-1303/BNT323 Dose Level 3 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 3 on Day 1 of each cycle Q3W

Group VI: DB-1303/BNT323 Dose Level 2 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 2 on Day 1 of each cycle Q3W

Group VII: DB-1303/BNT323 Dose Level 1 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 1 on Day 1 of each cycle Q3W

Group VIII: DB-1303/BNT323 Dose Expansion 9 Experimental Treatment 1 Intervention

Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 on Day 1 of each cycle Q3W

Group IX: DB-1303/BNT323 Dose Expansion 8 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group X: DB-1303/BNT323 Dose Expansion 7 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XI: DB-1303/BNT323 Dose Expansion 6 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XII: DB-1303/BNT323 Dose Expansion 5 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XIII: DB-1303/BNT323 Dose Expansion 4 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XIV: DB-1303/BNT323 Dose Expansion 3 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XV: DB-1303/BNT323 Dose Expansion 2 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XVI: DB-1303/BNT323 Dose Expansion 14 Experimental Treatment 1 Intervention

China Only:Subjects who were previously treated with trastuzumab and taxane will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XVII: DB-1303/BNT323 Dose Expansion 13 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XVIII: DB-1303/BNT323 Dose Expansion 12 Experimental Treatment 2 Interventions

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 in combination with Pertuzumab on Day 1 of each cycle Q3W

Group XIX: DB-1303/BNT323 Dose Expansion 11 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Group XX: DB-1303/BNT323 Dose Expansion 10 Experimental Treatment 3 Interventions

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W along with ritonavir or itraconazole to assess the DDI potential

Group XXI: DB-1303/BNT323 Dose Expansion 1 Experimental Treatment 1 Intervention

Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 Day 1 of each cycle Q3W

DB-1303 is already approved in United States for the following indications:

Approved in United States as BNT323/DB-1303 for:

• Advanced endometrial cancer (Breakthrough Therapy designation)

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

Bispecific antibodies (bsAbs) are being developed to target multiple antigens simultaneously in solid tumors, addressing the limitations of monoclonal antibodies that often fail due to antigen loss or downregulation.

While bsAbs like blinatumomab have shown success in hematologic cancers, their application in solid tumors is challenged by factors such as target selection, biodistribution, and the immune-suppressive tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies. Antonarelli, G., Giugliano, F., Corti, C., et al.[2023]

Bispecific antibodies (bsAbs) have been developed to target multiple oncogenic pathways and immune regulatory molecules simultaneously, which may help overcome resistance seen with traditional monoclonal antibody therapies in cancer treatment.

While some bsAbs are already approved for hematologic malignancies, there are currently no approved bsAbs for solid tumors, highlighting both the potential and the challenges in advancing these therapies for broader cancer applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies: A Novel Approach for the Treatment of Solid Tumors. Liguori, L., Polcaro, G., Nigro, A., et al.[2022]

CD133 is expressed in breast cancer cells, particularly in those with a triple negative phenotype, and is associated with increased malignancy, metastasis, and drug resistance.

The review highlights potential strategies to lower CD133 levels in breast tumors, which could help reduce tumor aggressiveness and prevent disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD133 in Breast Cancer Cells: More than a Stem Cell Marker. Brugnoli, F., Grassilli, S., Al-Qassab, Y., et al.[2020]

The immunotoxin dCD133KDEL effectively targets and inhibits growth in breast cancer cells with CD133(+) subpopulations, suggesting its potential to combat tumor-initiating cells.

Systemic administration of dCD133KDEL not only regressed tumors in a mouse model of metastatic breast cancer but also showed enhanced efficacy when combined with another immunotoxin, indicating its promise for combination therapies to tackle tumor heterogeneity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotoxin targeting CD133(+) breast carcinoma cells. Ohlfest, JR., Zellmer, DM., Panyam, J., et al.[2022]

The AC133×CD3 bispecific antibody (bsAb) effectively targets and induces the destruction of AC133-positive glioblastoma stem cells (GBM-SCs), showing strong potential in preventing tumor growth in preclinical models.

Importantly, this bsAb selectively spares normal hematopoietic stem cells, indicating a promising safety profile while maintaining effective treatment against invasive GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Eradication of Glioblastoma Stem Cells by Local Application of an AC133/CD133-Specific T-cell-Engaging Antibody and CD8 T Cells. Prasad, S., Gaedicke, S., Machein, M., et al.[2016]

Citations

1. 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 ...

2. 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 candidate has exhibited antitumor activity in both HER2-positive and HER2-low tumor models as well as in several solid tumor indications, ...

3. 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.

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 ... We are committed to advancing BNT323/DB-1303 with the aim to improve outcomes for patients in late disease stages.” In addition to the phase 1/2 ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05150691

A Phase 1/2a Study of DB-1303/BNT323 in Advanced ... Data from patients with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) advanced endometrial carcinoma are expected in 2025. A confirmatory Phase 3 clinical ...

6. investors.biontech.de investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-initiate-pivotal-phase-3-trial-antibody

BioNTech and DualityBio Initiate Pivotal Phase 3 Trial Of ... BNT323/DB-1303 was well tolerated with a manageable safety profile across all evaluated patients with advanced/metastatic solid tumors. The ...

7. 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.