DB-1311 + BNT327/DB-1305 for Solid Tumors

Recruiting at 44 trial locations

Overseen By Jay Ma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: DualityBio Inc.

Must not be taking: B7H3 therapy, Topoisomerase inhibitors

Disqualifiers: Cardiovascular disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 weeks

492 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for people with advanced solid tumors, specifically cancers such as liver, cervical, melanoma, head and neck, and certain lung cancers. Researchers are testing a combination of experimental drugs, including DB-1311, BNT327, and DB-1305 (also known as BNT325), to determine the best dose and observe their combined effects against these hard-to-treat cancers. This trial suits those whose cancer is advanced or cannot be surgically removed. Participants must have a confirmed diagnosis of one of these specific cancers and must not have received certain prior treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer 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 trial treatment, but it does not specify which medications need to be stopped. It's best to discuss your current medications with the trial team to understand what changes might be necessary.

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

In earlier studies, DB-1311/BNT324 proved generally safe for patients, with few serious blood-related side effects. Another study found that DB-1305/BNT325 was safe for patients with advanced solid tumors, showing early signs of effectiveness against tumors and being mostly well-tolerated.

Research demonstrated that BNT327 was safe for patients with solid tumors when combined with chemotherapy, yielding promising results without major side effects.

Overall, these treatments have shown safety for most participants in earlier studies, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments DB-1311, BNT327, and DB-1305 because they offer innovative approaches to tackling solid tumors. Unlike traditional chemotherapy that broadly attacks cancer cells, these treatments are designed to target specific cancer pathways, potentially leading to more effective and less toxic results. DB-1311, in particular, utilizes a novel mechanism that could potentially enhance the body's immune response to cancer. Meanwhile, BNT327 is being studied for its unique ability to disrupt cancer cell signaling pathways, which is critical for tumor growth. This targeted approach may lead to better outcomes for patients with challenging cancers like HCC, melanoma, and NSCLC, offering hope for results that current treatments may not achieve.

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

Studies have shown that the combination of DB-1311 and BNT324 holds promise in fighting tumors, particularly in patients with advanced solid tumors. Researchers have found it effective and safe, with few serious side effects. In this trial, some participants will receive DB-1311/BNT324 with BNT327, while others will receive DB-1311/BNT324 with DB-1305/BNT325. Research suggests that adding either BNT327 or DB-1305/BNT325 may enhance the combination's effectiveness because they boost each other's effects. Previous findings indicate these combinations can help manage tumors that resist standard treatments. Overall, the initial data is encouraging for those with advanced or metastatic solid tumors. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including uterine tumors. Participants must have a life expectancy of at least 3 months, be in good physical condition (ECOG score 0-1), and have proper organ function. They should not have had certain prior treatments like B7H3 targeted therapy or topoisomerase inhibitor antibody-drug conjugates.

Inclusion Criteria

Has a life expectancy of ≥ 3 months

I am fully active or can carry out light work.

My organs are functioning well enough for me to join a study.

Exclusion Criteria

I have serious heart problems that are not under control.

I have been treated with B7H3 targeted therapy before.

I have been treated with a specific cancer drug linked to a toxin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating combination dose levels of DB-1311/BNT324 and either BNT327 or DB-1305/BNT325 to define RP2D and RP2D-1 in the target population

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BNT327
• DB-1305/BNT325
• DB-1311

Trial Overview The study tests DB-1311 combined with either BNT327 or DB-1305 on participants with advanced solid tumors. It's an open-label Phase II trial, meaning both the researchers and participants know which treatment is being administered.

How Is the Trial Designed?

Group I: Part2 Arm 3:RP2D of DB-1311/BNT324 + BNT327 Experimental Treatment 2 Interventions

In participants with unresectable advanced/metastatic melanoma

Group II: Part 2 Arm 5: RP2D of DB-1311/BNT324 +DB-1305/BNT325 and RP2D-1 of DB-1311/BNT324 +DB-1305/BNT325 Experimental Treatment 2 Interventions

In participants with advanced/unresectable metastatic NSCLC

Group III: Part 2 Arm 4: RP2D of DB-1311/BNT324 + BNT327 and RP2D-1 of DB-1311/BNT324 + BNT327 Experimental Treatment 2 Interventions

In participants with recurrent/metastatic HNSCC

Group IV: Part 2 Arm 2: RP2D of DB-1311/BNT324 + BNT327 Experimental Treatment 2 Interventions

In participants with unresectable advanced/ metastatic CC

Group V: Part 2 Arm 1: RP2D of DB-1311/BNT324 + BNT327 Experimental Treatment 2 Interventions

In participants with unresectable advanced/metastatic HCC

Group VI: Part 1 Cohort 2, DB-1311/BNT324+ DB-1305 /BNT325 combination therapy Experimental Treatment 2 Interventions

Escalating combination dose levels of DB-1311/BNT324 and DB-1305/BNT325 to define RP2D and RP2D-1 in target population.

Group VII: Part 1 Cohort 1B, DB-1311/BNT324+ BNT327 combination therapy Experimental Treatment 2 Interventions

Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D and RP2D-1 in target population.

Group VIII: Part 1 Cohort 1A, DB-1311/BNT324+ BNT327 combination therapy Experimental Treatment 2 Interventions

Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D (Recommended Phase 2 Dose) and RP2D-1 in target population.

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

In a study of 42 patients with advanced non-small cell lung cancer (NSCLC), the combination of navelbine (NVB) and cisplatin (DDP) resulted in a partial response rate of 47.6%, indicating significant efficacy in treating this cancer.

The treatment was associated with manageable toxicity, primarily neutropenia, affecting 66.6% of patients, while also showing that higher doses of NVB led to better response rates, suggesting a dose-response relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Navelbine plus cisplatin combination therapy in the treatment of advanced non-small cell lung cancer: a report of 42 cases]. Zhang, X., Sun, Y., Kong, W.[2018]

In a phase II study involving 115 patients with metastatic breast cancer who had previously received anthracycline treatment, the combination of oral vinorelbine and capecitabine demonstrated a promising objective response rate of 56.5%, with 19.1% achieving a complete response.

The treatment was well tolerated, with only 0.8% of patients experiencing febrile neutropenia, and resulted in a median progression-free survival of 10.5 months and a median overall survival of 17.5 months, indicating both efficacy and safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of oral vinorelbine and capecitabine in anthracycline pretreated patients with metastatic breast cancer. Finek, J., Holubec, L., Svoboda, T., et al.[2022]

Citations

1. 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 ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)02506-2/abstract

1017eTiP A phase II trial of DB-1311/BNT324 (B7H3 ADC) ... Combining DB-1311/BNT324+ BNT327 (Combo 1) or DB-1311/BNT324 + DB-1305/BNT325 (Combo 2) may enhance antitumor efficacy through synergistic mechanisms.

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-b7-h3-antibody-drug-conjugate-db-1311

Clinical Trials Using Anti-B7-H3 Antibody-drug Conjugate ... A Phase 1/2a Study of DB-1311/BNT324 in Advanced/Metastatic Solid Tumors ... Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer.

4. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/160832-asco-2025-db-1311-bnt324-a-novel-b7h3-adc-in-patients-with-heavily-pretreated-crpc.html

ASCO 2025: DB‑1311/BNT324 (A Novel B7H3 ADC) in ... This phase 1/2 study enrolled patients with advanced/metastatic solid tumors, including. The primary endpoints were objective response rate ( ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05914116

A Phase 1/2a Study of DB-1311/BNT324 in Advanced/ ... A phase 1/2a, multicenter, open-label, first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1311.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06449222

Study Details | NCT06449222 | Safety and Preliminary ... This study is a Phase II, multi-site, randomized, open-label clinical study to evaluate the safety, efficacy, and pharmacokinetics (PK) of BNT327 at two ...

7. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/BNT327-02

Safety and Preliminary Effectiveness of BNT327, an ... This study is a Phase II, multi-site, randomized, open-label clinical study to evaluate the safety, efficacy, and pharmacokinetics (PK) of BNT327 at two dose ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/PS3-08/754094/Abstract-PS3-08-Interim-Overall-Survival-of

Abstract PS3-08: Interim Overall Survival of Patients with ... First-line therapy with PM8002/BNT327 combined with nab-paclitaxel showed clinically meaningful survival outcomes and antitumor activity regardless of PD-L1 ...

9. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-pd-l1-anti-vegf-a-bispecific-antibody-bnt327?pn=1

Clinical Trials Using Anti-PD-L1/Anti-VEGF-A Bispecific ... Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Breast Cancer, When Given in Combination With Chemotherapy · First-in-human Study ...

10. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01815-5/fulltext

348MO A phase Ib/II study to assess the safety and efficacy ... PM8002/BNT327 is a bispecific antibody targeting PD-L1 and VEGF-A developed for the treatment of solid tumors. We conducted a Phase Ib/II study of PM8002 in ...