D3L-001 for Solid Tumors

Recruiting in Palo Alto (17 mi)

+7 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: D3 Bio (Wuxi) Co., Ltd

Must not be taking: Anti-CD47, SIRPα agents

Disqualifiers: Uncontrolled illness, unresolved toxicities, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called D3L-001 for patients with advanced cancers that have a specific protein called HER2. The study aims to see if the drug is safe and how it affects the body. Researchers hope that D3L-001 will help slow down or stop the growth of these tumors.

Will I have to stop taking my current medications?

The trial requires that you stop taking any immunosuppressive medications at least 14 days before starting the study medication. Other anticancer treatments must be completed 28 days before the first dose.

What data supports the effectiveness of the drug D3L-001 for treating solid tumors?

Research shows that bispecific antibodies, like D3L-001, can block CD47, a protein that helps cancer cells avoid the immune system, and target HER2, a protein found in some cancer cells. This approach has been shown to stop tumor growth and activate immune cells to fight cancer in studies, suggesting it could be effective for solid tumors. ^{1 2 3 4 5}

What safety data exists for D3L-001 or similar treatments?

Research on similar treatments, like CD47-targeting bispecific antibodies, shows they can be effective against tumors with minimal side effects, such as limited impact on red blood cells, in non-human primates. This suggests a potential for safe use in humans, but specific safety data for D3L-001 is not detailed in the available research. ^{1 4 6 7 8}

What makes the drug D3L-001 unique for treating solid tumors?

D3L-001 is unique because it is a bispecific antibody that targets both CD47 and HER2, enhancing the immune system's ability to attack tumor cells while potentially reducing the safety issues associated with targeting CD47 alone. This dual targeting approach may improve the effectiveness of treatment by promoting a stronger immune response against tumors. ^{1 3 8 9 10}

Research Team

Eligibility Criteria

This trial is for people with advanced solid tumors that test positive for HER2. Participants should be relatively healthy and active (ECOG status of 0 or 1), have a heart pumping function (LVEF) of at least 50%, and good organ/marrow function. They can't join if they've had certain cancer treatments, major surgery, or immunosuppressive meds within specific time frames before the study starts.

Inclusion Criteria

My cancer is HER2 positive, confirmed by a lab test.

I am fully active or can carry out light work.

My heart pumps well, with an ejection fraction of 50% or higher.

Exclusion Criteria

I have side effects from cancer treatment that are not just hair loss or skin changes.

I have previously been treated with anti-CD47 or SIRPα agents.

Subject has uncontrolled intercurrent illness that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of D3L-001 to evaluate safety and tolerability

8-12 weeks

Dose Expansion

Participants receive D3L-001 at the determined dose to further evaluate efficacy in specific cancer types

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• D3L-001 (Monoclonal Antibodies)

Trial Overview The trial is testing D3L-001 as a solo treatment to see how safe it is, how the body handles it (PK/PD), if it causes an immune response, and whether it works against HER2-positive tumors. It's in Phase I which means this is the first time humans are trying it out.

Participant Groups

Group I: D3L-001 Experimental Treatment 1 Intervention

Part 1 Dose Escalation in subjects with HER2-positive advanced solid tumors * Cohort 1 (starting dose) * Cohort 2 * Cohort 3 * Cohort 4 * Cohort 5 Part 2 Dose Expansion * Cohort A for subjects with HER2-positive advanced breast cancer * Cohort B for subjects with HER2-positive advanced gastric cancer/gastroesophageal junction cancer

Who Is Running the Clinical Trial?

D3 Bio (Wuxi) Co., Ltd

Lead Sponsor

Trials

3

Recruited

560+

Findings from Research

Bispecific antibodies targeting the EGF-receptor and immune effector cell receptors significantly enhance tumor cell killing compared to conventional monoclonal antibodies, indicating improved efficacy in treating renal cell carcinoma.

Using whole blood from patients treated with myeloid growth factors like G-CSF or GM-CSF, the bispecific antibodies showed the highest cytotoxicity, with granulocytes identified as the most effective immune cells in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma. Elsässer, D., Stadick, H., Stark, S., et al.[2018]

Bispecific antibodies have demonstrated the ability to selectively target and effectively eliminate malignant T cells in both laboratory (in vitro) and living organism (in vivo) settings.

This selectivity and efficacy suggest that bispecific antibodies could be a promising therapeutic approach for treating cancers involving T cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell Malignancies Can Be Targeted by Bispecific Antibody Treatments. [2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Multiformat T-cell-engaging bispecific antibodies targeting human breast cancers. [2018]

3. Greece pubmed.ncbi.nlm.nih.gov

Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma. [2018]

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

Development of Bispecific Antibody Derivatives for Cancer Immunotherapy. [2019]

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

T-cell Malignancies Can Be Targeted by Bispecific Antibody Treatments. [2021]

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

An optimized IgG-based B7-H3xCD3 bispecific antibody for treatment of gastrointestinal cancers. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies for the treatment of tumours and infectious diseases. [2019]

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

Bispecific HER2 x CD3 antibodies enhance T-cell cytotoxicity in vitro and localize to HER2-overexpressing xenografts in nude mice. [2019]