DB-1305 for Solid Tumors

Recruiting at 2 trial locations

Overseen By Cathy Li

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 1 & 2

Sponsor: DualityBio Inc.

Disqualifiers: Heart failure, Myocardial infarction, ILD, 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: Unknown

902 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety and tolerability of a new treatment, DB-1305 (also known as BNT325/DB-1305), for individuals with advanced solid tumors unresponsive to standard treatments. Researchers test various doses of DB-1305, both alone and with other cancer drugs, to determine the most effective doses. Individuals with advanced or metastatic solid tumors who have not benefited from other treatments may qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires an adequate treatment washout period (time without taking certain medications) before starting the study, which suggests you may need to stop some current medications. 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-1305, also known as BNT325, has a safety profile that doctors find acceptable for patients with advanced or spreading solid tumors. This means the side effects and risks fall within a manageable range.

Earlier studies indicated early signs that the treatment might help fight tumors, which is encouraging. It was tested on individuals who had not responded to other treatments, and it showed some positive results in these cases. This suggests that DB-1305 is tolerated well enough for further research.

Since this clinical trial is in its early stages (Phase 1/2), it focuses on finding the right dose and learning more about the treatment's safety. This is a normal part of developing new treatments to ensure they are safe for wider use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

DB-1305 is unique because it introduces a novel mechanism of action for treating solid tumors. Unlike traditional chemotherapy, which often targets rapidly dividing cells indiscriminately, DB-1305 is designed to target specific molecular markers on cancer cells, potentially leading to more precise and effective treatment. Researchers are excited about this treatment because it could offer a more targeted approach, potentially reducing side effects and improving outcomes for patients with solid tumors. Additionally, the trial explores combinations with other treatments like pembrolizumab, which may enhance its effectiveness by activating the immune system against cancer cells.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that DB-1305/BNT325 offers promising results for treating advanced solid tumors. In earlier studies, patients with various solid tumors, including those unresponsive to other treatments, demonstrated positive outcomes. For instance, some patients with ovarian cancer resistant to platinum-based treatments experienced tumor shrinkage or halted growth, suggesting potential effectiveness. The drug targets Trop-2, a protein often abundant on cancer cells, which helps deliver the medication directly to the tumor. This approach aims to kill cancer cells while minimizing harm to normal cells. Overall, these early findings suggest that DB-1305/BNT325 could be a promising option for treating solid tumors. Participants in this trial will receive DB-1305/BNT325 at various dose levels or in combination with other treatments to further evaluate its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Lily Hu

Principal Investigator

DualityBio Inc.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that have worsened after standard treatments or when no standard treatment exists. Participants must be willing to provide tumor samples, have a life expectancy of at least 3 months, be in good physical condition (ECOG 0-1), and have proper organ function.

Inclusion Criteria

Do you have one of the following types of cancer?: Mesothelioma, Non-Small Cell Lung Cancer, Cervical Cancer, Endometrial Cancer, or Breast Cancer?

Is your cancer HER2 positive?

Would you be willing to provide a pre-existing tumor sample or undergo a biopsy?

Exclusion Criteria

Have you had a medical history of symptomatic congestive heart failure (CHF), interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or current interstitial lung diseases?

Do you currently have an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals, or do you currently have or have had human immunodeficiency virus (HIV) infection with acquired immune deficiency syndrome (AIDS) defining illness?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 adopts an accelerated titration at first dose level followed with classic '3+3' design to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D)

Approximately 12 months

Dose Expansion

Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D

Approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 days after last study treatment administration

What Are the Treatments Tested in This Trial?

Interventions

• DB-1305

Trial Overview DB-1305 is being tested for safety and effectiveness in treating advanced solid tumors. This early-phase trial gradually increases the dose to find the right balance between benefits and side effects before expanding to more patients.

How Is the Trial Designed?

Group I: Experimental: DB-1305/BNT325 in combination with BNT327 Experimental Treatment 2 Interventions

Enrolled subjects will receive DB-1305/BNT325 in combination with BNT327

Group II: Experimental: DB-1305/BNT325 Dose Level 8 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 8

Group III: Experimental: DB-1305/BNT325 Dose Expansion PM5 Experimental Treatment 2 Interventions

Enrolled subjects with TNBC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Group IV: Experimental: DB-1305/BNT325 Dose Expansion PM4 Experimental Treatment 2 Interventions

Enrolled subjects with OC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Group V: Experimental: DB-1305/BNT325 Dose Expansion PM3 Experimental Treatment 2 Interventions

Enrolled subjects with CC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Group VI: Experimental: DB-1305/BNT325 Dose Expansion PM2 Experimental Treatment 2 Interventions

Enrolled subjects with NSCLC with AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Group VII: Experimental: DB-1305/BNT325 Dose Expansion PM1 Experimental Treatment 2 Interventions

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Group VIII: Experimental: DB-1305/BNT325 Dose Expansion 10 Experimental Treatment 1 Intervention

Enrolled subjects with pancreatic cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group IX: DB-1305/BNT325 in combination with pembrolizumab Experimental Treatment 2 Interventions

Enrolled subjects will receive DB-1305/BNT325 in combination with pembrolizumab

Group X: DB-1305/BNT325 Dose Level 7 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 7

Group XI: DB-1305/BNT325 Dose Level 6 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 6

Group XII: DB-1305/BNT325 Dose Level 5 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 5

Group XIII: DB-1305/BNT325 Dose Level 4 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 4

Group XIV: DB-1305/BNT325 Dose Level 3 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 3

Group XV: DB-1305/BNT325 Dose Level 2 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 2

Group XVI: DB-1305/BNT325 Dose Level 1 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 1

Group XVII: DB-1305/BNT325 Dose Expansion PB1 Experimental Treatment 2 Interventions

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with pembrolizumab

Group XVIII: DB-1305/BNT325 Dose Expansion 9 Experimental Treatment 1 Intervention

Enrolled subjects with Cervical Cancer (CC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XIX: DB-1305/BNT325 Dose Expansion 8 Experimental Treatment 1 Intervention

Enrolled subjects with malignant mesothelioma will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XX: DB-1305/BNT325 Dose Expansion 7 Experimental Treatment 1 Intervention

Enrolled subjects with EC who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XXI: DB-1305/BNT325 Dose Expansion 6 Experimental Treatment 1 Intervention

Enrolled subjects with TNBC with treatment failure on sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XXII: DB-1305/BNT325 Dose Expansion 5 Experimental Treatment 1 Intervention

Enrolled subjects with Triple-Negative Breast Cancer (TNBC) who have progressed on or after standard systemic treatments and without prior treatment of sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XXIII: DB-1305/BNT325 Dose Expansion 4 Experimental Treatment 1 Intervention

Enrolled subjects with BC who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XXIV: DB-1305/BNT325 Dose Expansion 3 Experimental Treatment 1 Intervention

Enrolled subjects with OC who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Group XXV: DB-1305/BNT325 Dose Expansion 2 Experimental Treatment 1 Intervention

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Group XXVI: DB-1305/BNT325 Dose Expansion 12 Experimental Treatment 1 Intervention

Enrolled subjects with head and neck cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XXVII: DB-1305/BNT325 Dose Expansion 11 Experimental Treatment 1 Intervention

Enrolled subjects with Castration-Resistant Prostate Cancer (CRPC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Group XXVIII: DB-1305/BNT325 Dose Expansion 1 Experimental Treatment 1 Intervention

subjects with Non-Small Cell Lung Cancer (NSCLC) with actionable genetic alterations (AGAs) who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

DB-1305 is already approved in United States for the following indications:

Approved in United States as BNT325/DB-1305 for:

• Platinum-resistant ovarian epithelial cancer
• Fallopian tube cancer
• Primary peritoneal 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

The combination chemotherapy of NVB and DDP showed a 53.8% overall response rate in 52 patients with advanced non-small cell lung cancer, indicating its effectiveness as a treatment option.

The main side effects included leucopenia, nausea, vomiting, and phlebitis, but these were generally well tolerated, suggesting that the NP regimen can be considered a viable first-line treatment for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[NVB and DDP combination chemotherapy in the treatment of advanced non-small cell lung cancer]. Jiang, H., Fan, Y., Yu, D.[2011]

Vinorelbine combined with cisplatin shows an overall response rate of 30.9% in treating inoperable non-small cell lung cancer (NSCLC), with a median survival duration of 8.3 months based on a study of 220 patients.

The treatment is generally well-tolerated, although the main side effects include myelosuppression and digestive tract reactions, with myelosuppression identified as the dose-limiting toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical research on combined chemotherapy of vinorelbine and cisplatin in the treatment of non-small cell lung cancer]. Xu, L., Zhu, Y., You, Y., et al.[2011]

In a phase I study involving 38 patients with refractory solid tumors, the maximum tolerated doses (MTD) for vinorelbine and oxaliplatin were determined to be 27 mg/m2 and 50 mg/m2, respectively, with notable dose-limiting toxicities including grade 4 neutropenia.

The combination treatment showed some efficacy, with 4% achieving complete response and 20% partial response, particularly in patients with ovarian and breast cancer, suggesting potential for further evaluation in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose-escalation study of oxaliplatin and vinorelbine in patients with advanced solid tumors. Kakolyris, S., Kouroussis, C., Koukourakis, M., et al.[2018]

Technological advances in cancer research are revealing new therapeutic targets and enhancing our understanding of tumors, but therapy resistance remains a significant challenge for advanced cancers, limiting the effectiveness of single-agent treatments.

With around 5,000 clinical trials exploring combination therapies, there is a need for more rational design of these combinations based on biological insights to avoid issues like missed opportunities and clinical failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational Cancer Treatment Combinations: An Urgent Clinical Need. Boshuizen, J., Peeper, DS.[2020]

Combination chemotherapy using navelbine (NVB) and cisplatin (DDP) resulted in a 47.8% overall response rate in 46 patients with advanced non-small cell lung cancer (NSCLC), with a median survival time of 9.5 months and a one-year survival rate of 39.1%.

The treatment was associated with manageable toxicities, primarily myelosuppression and nausea/vomiting, indicating that while side effects occurred, they were tolerable for patients undergoing this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of navelbine combined with cisplatin in the treatment of advanced non-small cell lung cancer]. He, Y.[2011]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02712-6/fulltext

689P DB-1305 (a Trop-2 targeted antibody-drug-conjugate ... Pts with advanced solid tumors who had failed standard therapy were enrolled. In Ph1, DB-1305 was planned to be administered from 2 mg/kg to 8 mg/kg (Q3W, iv) ...

2. clin.larvol.com clin.larvol.com/trial-detail/NCT05438329

First-in-human Study of DB-1305/BNT325 for Advanced ... Across the 13 efficacy evaluable patients with PROC, seven patients achieved partial response and three stable disease. Responses were also observed in patients ...

3. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-bnt325-db-1305-for-platinum-resistant-ovarian-cancer

FDA Grants Fast Track Designation to BNT325/DB-1305 ... “Data from the phase 1/2 clinical trial with BNT325/DB-1305 have demonstrated encouraging anti-tumor signals in heavily pretreated patients with ...

4. investors.biontech.de investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-receive-fda-fast-track-designation-next

BioNTech and DualityBio Receive FDA Fast Track ... BNT325/DB-1305 has exhibited antitumor activity in tumor models as well as in several advanced solid tumor indications, including non-small cell ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06953089

NCT06953089 | DB-1311 in Combination With BNT327 or ... This is a phase II, multicenter, open-label, two-part trial designed to evaluate the safety and preliminary efficacy of DB-1311 in combination with BNT327 ...

6. en.dualitybiologics.com en.dualitybiologics.com/17335757308177/newpath17336570213359/15.html

DB-1305 /BNT325 Well-positioned to address underserved needs in OC, NSCLC and TNBC. Combination potential as backbone therapy in multiple solid tumors (NSCLC, TNBC, OC, CC).