DB-1311 for Advanced Cancer

Recruiting at 117 trial locations

Overseen By Tiana Zhao

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: DualityBio Inc.

Must not be taking: B7-H3 therapy, Topoisomerase inhibitors

Disqualifiers: Heart failure, Lung diseases, Infections, others

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

Compensation: Varies

Number of Visits: 1

Duration: 21-day cycles, up to 12 months

862 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, DB-1311, for individuals with advanced solid tumors unresponsive to standard treatments. Participants will receive the treatment through an intravenous infusion, typically once every three weeks. The trial seeks individuals with advanced or metastatic cancers, such as small cell lung cancer, non-small cell lung cancer, esophageal cancer, or other types that have not responded to standard care. It suits those who have tried standard cancer treatments without success and are seeking new options. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive it.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to stop any drugs that are known to prolong the QT interval (a heart rhythm measure). It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that DB-1311/BNT324 is likely to be safe for humans?

Studies have shown that DB-1311/BNT324 is generally safe for patients with advanced cancer. In earlier research, patients with advanced prostate cancer who had already tried several treatments tolerated DB-1311/BNT324 well. Reports indicate that side effects were usually manageable, meaning they weren't too severe or difficult to handle. This suggests that the treatment is fairly well-tolerated, although some side effects can still occur. Ongoing studies are testing the treatment further to confirm its safety and effectiveness in more patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about DB-1311/BNT324 because it offers a fresh approach to treating advanced cancers that have resisted traditional therapies. Unlike standard treatments like chemotherapy or targeted therapies, DB-1311/BNT324 is administered via intravenous infusion every three weeks, which might improve patient compliance and convenience. Additionally, this investigational drug is being tested at various dose levels to optimize its effectiveness and safety, offering hope for a personalized treatment strategy that could be more effective for patients with advanced or metastatic cancers such as SCLC, NSCLC, ESCC, and others.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that DB-1311/BNT324, a new cancer treatment, is yielding promising early results for advanced cancers. In one study with 393 patients, about 29% experienced a reduction in tumor size. This treatment targets a protein called B7H3, often found in large amounts on cancer cells, enabling the drug to attack the cancer more effectively. The FDA granted it Fast Track status for prostate cancer, highlighting its potential importance. This trial will explore DB-1311/BNT324 across various treatment arms, each focusing on different advanced solid tumors, to assess its effectiveness for patients who have not responded to other treatments. ^{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 for whom no standard treatment exists. Participants must be over 18, have a measurable tumor, an expected lifespan of at least 3 months, good performance status and heart function. They should agree to use contraception and not donate gametes during the trial.

Inclusion Criteria

I understand the study's procedures and risks, can consent in writing, and will follow the study requirements.

I am fully active or can carry out light work.

I will not donate or use my eggs for 7 months after the last study drug.

Exclusion Criteria

I have heart failure or serious heart rhythm problems that need treatment.

I have been treated with a specific cancer drug linked to a toxin (like trastuzumab deruxtecan).

I do not have active hepatitis, or if I have had hepatitis B or C, it is under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Phase 1 involves dose-escalation to identify the MTD and RP2D using an accelerated titration and '3+3' design, followed by Phase 2a dose expansion to confirm safety and explore efficacy

21-day cycles, up to 12 months

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 1 year post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• DB-1311

Trial Overview The safety and effectiveness of DB-1311 are being tested in adults with advanced solid tumors. This Phase 1/2a trial will gradually increase doses to find the safest dose that can still work effectively.

How Is the Trial Designed?

Group I: DB-1311/BNT324 Dose Level 5 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1311/BNT324 at Dose Level 5 on Day 1 of each cycle Q3W

Group II: DB-1311/BNT324 Dose Level 4 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1311/BNT324 at Dose Level 4 on Day 1 of each cycle Q3W

Group III: DB-1311/BNT324 Dose Level 3 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1311/BNT324 at Dose Level 3 on Day 1 of each cycle Q3W

Group IV: DB-1311/BNT324 Dose Level 2 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1311/BNT324 at Dose Level 2 on Day 1 of each cycle Q3W

Group V: DB-1311/BNT324 Dose Level 1 Experimental Treatment 1 Intervention

Enrolled Subjects will receive a single-dose of DB-1311/BNT324 at Dose Level 1 on Day 1 of each cycle Q3W (every 3 weeks)

Group VI: DB-1311/BNT324 Dose Expansion 9 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic HNSCC (not including nasopharyngeal carcinoma \[NPC\]) who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group VII: DB-1311/BNT324 Dose Expansion 8 Experimental Treatment 1 Intervention

Subjects with other advanced or metastatic solid tumors who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group VIII: DB-1311/BNT324 Dose Expansion 7 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic cervical cancer who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group IX: DB-1311/BNT324 Dose Expansion 6 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic HCC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group X: DB-1311/BNT324 Dose Expansion 5 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic melanoma who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group XI: DB-1311/BNT324 Dose Expansion 4 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic CRPC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324 randomized at dose level 1 or 2.

Group XII: DB-1311/BNT324 Dose Expansion 3 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic ESCC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group XIII: DB-1311/BNT324 Dose Expansion 2 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic NSCLC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324 randomized at dose level 1 or 2.

Group XIV: DB-1311/BNT324 Dose Expansion 18 Experimental Treatment 3 Interventions

CSPC subjects with suboptimal PSA response to ADT/NHT, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324, combined with enzalutamide 160mg or abiraterone 1000mg QD orally.

Group XV: DB-1311/BNT324 Dose Expansion 17 Experimental Treatment 2 Interventions

Taxane-naive subjects with metastatic CRPC who have progressed on or after NHT, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324, combined with abiraterone 1000mg QD orally.

Group XVI: DB-1311/BNT324 Dose Expansion 16 Experimental Treatment 2 Interventions

Taxane-naive subjects with metastatic CRPC who have progressed on or after NHT, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324, combined with enzalutamide 160mg QD orally.

Group XVII: DB-1311/BNT324 Dose Expansion 15 Experimental Treatment 3 Interventions

Subjects with Subjects with advanced/unresectable, or metastatic melanoma, ESCC, PROC and CC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via IV will be used for DB-1311/BNT324. Lopinavir and ritonavir/ Itraconazole will be administered orally twice a day/ once a day.

Group XVIII: DB-1311/BNT324 Dose Expansion 14 Experimental Treatment 1 Intervention

Subjects with epithelial OC who have had 1-3 prior lines of systemic treatment and are platinum-resistant, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324 randomized at dose level 1 or 2.

Group XIX: DB-1311/BNT324 Dose Expansion 13 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic HNSCC (not including NPC) who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group XX: DB-1311/BNT324 Dose Expansion 12 Experimental Treatment 1 Intervention

Taxane-naive subjects with metastatic CRPC who have progressed on or after novel hormone therapy, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group XXI: DB-1311/BNT324 Dose Expansion 11 Experimental Treatment 1 Intervention

Subjects with metastatic CRPC who have progressed on or after standard systemic treatments including no more than 2 lines of systemic chemotherapy, novel hormone therapy and lutetium-177 radioligand therapy, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group XXII: DB-1311/BNT324 Dose Expansion 10 Experimental Treatment 1 Intervention

Subjects with advanced or metastatic rare tumor types who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324.

Group XXIII: DB-1311/BNT324 Dose Expansion 1 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or metastatic SCLC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311/BNT324 randomized at dose level 1 or 2.

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

C-1311, an anticancer agent, was tested in a phase 1 trial with 22 patients, showing a recommended dose of 480 mg/m² that provided a predictable safety profile and good tolerability, despite all patients experiencing treatment-related adverse events.

The most common side effects included neutropenia and nausea, with some severe cases of neutropenia, indicating that while C-1311 has potential anti-tumor activity, careful monitoring of blood-related side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours. Isambert, N., Campone, M., Bourbouloux, E., et al.[2017]

The study demonstrated that 131I-anti hnRNPB1 monoclonal antibody (MAb) effectively inhibits tumor growth in mice with Lewis lung carcinoma, with a significant reduction in tumor volume observed in groups receiving the treatment compared to the control group.

A dose-response relationship was established, showing that administering double doses of 131I-anti hnRNPB1 MAb resulted in a greater tumor growth inhibition rate (67.17%) compared to a single dose (39.03%), highlighting the importance of dosage in therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental study for the targeting therapy of mouse lung carcinoma treated by anti-hnRNPB1 monoclonal antibody with 131I]. Chen, MY., Li, WM., Xu, D., et al.[2012]

In a study involving 12 patients with advanced metastatic breast cancer, 50% experienced significant tumor regressions of over 30%, with four patients achieving a partial response of at least 50% reduction in tumor size after treatment with 131I chimeric L6 monoclonal antibody therapy.

The maximum tolerated dose (MTD) for the therapy was determined to be 60 mCi/m2 without stem cell support, while higher doses (up to 150 mCi/m2) were administered safely with autologous stem cell support, indicating the potential for effective radioimmunotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of radioimmunotherapy in advanced breast cancer using I-131 chimeric L6. DeNardo, SJ., O'Grady, LF., Richman, CM., et al.[2019]

In a phase II trial involving 25 patients with relapsed B-cell lymphomas, treatment with 131I-labelled anti-CD20 antibody resulted in 18 out of 21 patients showing objective responses, including 16 complete remissions.

The therapy demonstrated a high overall survival rate of 93% and a progression-free survival rate of 62% over a median follow-up of 2 years, indicating its efficacy in producing long-lasting responses in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Press, OW., Eary, JF., Appelbaum, FR., et al.[2019]

In a study using a nude mouse model, combining low-dose 131I-labeled monoclonal antibody A33 with 5-fluorouracil (5-FU) significantly enhanced tumor reduction compared to using either treatment alone, indicating a potential additive antitumor effect.

Long-term survival results showed that 38% of mice treated with the combination of 5-FU and 131I-mAb A33 were disease-free after 276 days, suggesting a synergistic effect that supports further clinical trials for this combination therapy in colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil). Tschmelitsch, J., Barendswaard, E., Williams, C., et al.[2013]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5015

DB-1311/BNT324 (a novel B7H3 ADC) in patients with ... Results: As of 3 Jan 2025, of 393 pts treated with DB-1311/BNT324, there were 65 pts with CRPC. Median age was 71 years (range 45–84), 49%/34%/ ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05914116

NCT05914116 | A Phase 1/2a Study of DB-1311/BNT324 ... This is a multicenter, open-label, multiple-dose, FIH Phase 1/2a study. Phase 1 adopts an accelerated titration at first dose level followed with classic ...

3. 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 ... B7H3 antibody drug conjugates have reported early clinical activity in CRPC, including DB-1311/BNT324, an investigational B7H3 antibody drug ...

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

BioNTech and DualityBio Receive FDA Fast Track ... BioNTech and DualityBio Receive FDA Fast Track Designation for Antibody-Drug Conjugate Candidate BNT324/DB-1311 in Prostate Cancer. 24 June 2024.

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04134-6/fulltext

57O A phase I/II multicenter, first-in-human study of DB ... Preliminary efficacy from 77 response-evaluable pts showed 22 partial responses (PR) and 42 stable diseases, for an unconfirmed ORR of 28.6% (95% CI 18.9, 40.0) ...

6. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/DB-1311-O-1001

A Phase 1/2a Study of DB‑1311/BNT324 in Advanced/ ... This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1311/BNT324 in subjects with advanced solid tumors.