What is the mechanism of action of this treatment?

The most common treatments for HER2-positive solid tumors include monoclonal antibodies like trastuzumab and antibody-drug conjugates like T-DM1. Trastuzumab binds to the HER2 receptor on the surface of cancer cells, blocking them from receiving growth signals and marking them for destruction by the immune system. T-DM1 combines trastuzumab with a cytotoxic agent, delivering targeted chemotherapy directly to the cancer cells. These treatments are crucial for patients with HER2-positive solid tumors because they specifically target the overexpressed HER2 protein, leading to more effective and less toxic treatment compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for HER2-positive solid tumors, such as trastuzumab, lapatinib, and T-DM1, are generally well-tolerated but can have significant side effects. Trastuzumab is associated with cardiac dysfunction, chills, fever, nausea, vomiting, weakness, and headache. Lapatinib commonly causes diarrhea, rash, and hepatic adverse events. T-DM1 can lead to thrombocytopenia, elevated liver enzymes, and fatigue. General chemotherapy side effects, which may be experienced in combination with these targeted therapies, include neurotoxicity, granulocytopenia, anemia, and gastrointestinal symptoms.

What prior FDA approvals exist?

Several HER2 inhibitors have received FDA approval for the treatment of solid tumors. Trastuzumab, a monoclonal antibody targeting HER2, has been widely used in HER2-positive breast cancer and has shown significant improvements in progression-free survival (PFS) and overall survival (OS). Trastuzumab emtansine (T-DM1) is another approved HER2-targeted therapy that combines trastuzumab with a cytotoxic agent, showing improved outcomes in patients who have progressed on prior HER2-directed therapies. Additionally, neratinib, in combination with capecitabine, has been approved for advanced HER2-positive breast cancer after two or more prior anti-HER2-based regimens, demonstrating improved PFS. These treatments highlight the efficacy of HER2 inhibition in managing advanced solid tumors.

What other types of research exist?

Promising alternatives to DB-1303 for HER2-positive solid tumors include: 1) Trastuzumab Deruxtecan (Enhertu), which has shown significant efficacy in previously treated HER2-positive breast cancer. 2) Pertuzumab combined with Trastuzumab and Docetaxel, as demonstrated in the PUFFIN study for untreated HER2-positive metastatic breast cancer. 3) Trastuzumab Emtansine (T-DM1), which has been effective in pretreated HER2-positive advanced breast cancer. These therapies have demonstrated positive outcomes in clinical trials and are viable options for patients in 2024.

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Monoclonal Antibodies

DB-1303 for Solid Cancers

Phase 1 & 2

Recruiting

Research Sponsored by DualityBio Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has a pathologically documented HER2-positive or HER2-expressing (except for cohort 2h where the requirement is HER2-null), advanced/unresectable, recurrent, or metastatic malignant solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available

ECOG performance status (PS) of 0-1

Must not have

History of symptomatic CHF (New York Heart Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment

Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to follow-up period, approximately 1 year post-treatment

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects may include reactions related to the immune system, liver or kidney issues due to drug interactions, heart problems from Pertuzumab Injection, and general symptoms like nausea or fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is HER2-positive or expresses HER2, is advanced, and doesn't respond to standard treatments.

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I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of serious heart failure or heart rhythm problems needing treatment.

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I don't have lasting side effects from cancer treatment worse than mild.

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I have active brain tumors.

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I have a history of serious lung problems.

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I do not have an infection needing IV drugs.

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I have HIV with AIDS or active hepatitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to follow-up period, approximately 1 year post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to follow-up period, approximately 1 year post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to follow-up period, approximately 1 year post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0

Phase 1: Maximum Tolerated Dose (MTD) of DB-1303

Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.

+7 more

Secondary study objectives

Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1

Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1

Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1

+13 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

21Treatment groups

Experimental Treatment

Group I: DB-1303/BNT323 Dose Level 7Experimental Treatment1 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 6Experimental Treatment1 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 5Experimental Treatment1 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 4Experimental Treatment1 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 3Experimental Treatment1 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 2Experimental Treatment1 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 1Experimental Treatment1 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 9Experimental Treatment1 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 8Experimental Treatment1 Intervention