DB-1303 for Solid Cancers

Recruiting in Palo Alto (17 mi)

+81 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: DualityBio Inc.

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

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called DB-1303 to see if it is safe for patients with advanced solid tumors that express HER2. The study will begin with lower doses and increase them over time to find the highest dose that patients can handle. This helps determine the best dose for future studies.

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.

What makes the drug DB-1303 unique for treating solid cancers?

DB-1303 is unique because it is a bispecific antibody (bsAb) that targets specific proteins on cancer cells and immune cells simultaneously, potentially overcoming resistance seen with traditional monoclonal antibodies by engaging the immune system more effectively. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• DB-1303 (Monoclonal Antibodies)

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.

Participant Groups

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

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

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]

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]

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]

References

1. United States 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. [2016]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies. [2023]

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

Immunotoxin targeting CD133(+) breast carcinoma cells. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies: A Novel Approach for the Treatment of Solid Tumors. [2022]

5. Egypt pubmed.ncbi.nlm.nih.gov

CD133 in Breast Cancer Cells: More than a Stem Cell Marker. [2020]