DB-1311 for Advanced Cancer

Recruiting at 100 trial locations

Overseen By Tianna 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

610 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, DB-1311, in patients with advanced solid tumors. It aims to find the safest and most effective dose and then confirm its safety and effectiveness in more patients.

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.

What makes the drug DB-1311 unique for treating advanced cancer?

DB-1311 is unique because it belongs to the novel imidazoacridinone family of anticancer agents, which are being studied for their safety and potential anti-tumor activity in advanced solid tumors. This sets it apart from other treatments that may not use this specific class of compounds. ^{1 2 3 4 5}

Research Team

Lily Hu

Principal Investigator

DualityBio Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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

Subjects with advanced/unresectable, or metastatic HNSCC 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 castration-resistant prostate cancer (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.

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

Subjects with advanced/unresectable, or metastatic esophageal squamous cell carcinoma (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.

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

Taxane-naive subjects with advanced/unresectable, or 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 XV: DB-1311/BNT324 Dose Expansion 11 Experimental Treatment 1 Intervention

Subjects with advanced/unresectable, or 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 XVI: 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 XVII: 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.

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

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]

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]

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 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]

References

1. England 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. [2017]

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

Overview of radioimmunotherapy in advanced breast cancer using I-131 chimeric L6. [2019]

3. England 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. [2019]

4. China pubmed.ncbi.nlm.nih.gov

[Experimental study for the targeting therapy of mouse lung carcinoma treated by anti-hnRNPB1 monoclonal antibody with 131I]. [2012]

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

Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil). [2013]