D3L-001 for Solid Tumors

Recruiting at 7 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: D3 Bio (Wuxi) Co., Ltd

Must not be taking: Anti-CD47, SIRPα agents

Disqualifiers: Uncontrolled illness, unresolved toxicities, others

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

Compensation: Varies

Number of Visits: Unknown

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called D3L-001, an anti-CD47/anti-HER2 bispecific antibody, for individuals with HER2-positive advanced solid tumors, such as certain breast and stomach cancers. Researchers aim to assess the safety and tolerability of this treatment and to determine if it shows any tumor-fighting activity. The trial includes several stages to identify the appropriate dose and to explore how the treatment functions in the body. It suits those diagnosed with HER2-positive cancer who have not recently undergone specific cancer treatments. 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 this new therapy.

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.

Is there any evidence suggesting that D3L-001 is likely to be safe for humans?

Research has shown that D3L-001, a new type of antibody, targets two proteins called HER2 and CD47, helping the immune system attack cancer cells more effectively. In early lab studies, D3L-001 demonstrated strong effects against various solid tumors. However, this Phase 1 trial marks its first test in humans.

Phase 1 trials primarily focus on safety, so researchers aim to assess how well people tolerate D3L-001 and monitor for any side effects. While detailed safety information in humans isn't yet available, the Phase 1 trial prioritizes safety. As with any new treatment, risks may exist, but this stage will help identify them.

Researchers will closely monitor participants for any negative reactions to ensure their safety as the trial progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about D3L-001 because it targets HER2-positive advanced solid tumors with a novel approach. Unlike traditional treatments like trastuzumab or pertuzumab that primarily inhibit HER2 receptors, D3L-001 may have a unique mechanism of action or molecular structure designed to enhance effectiveness against these cancers. This could potentially lead to better outcomes for patients with HER2-positive advanced breast and gastric cancers, offering hope for those who have exhausted other treatment options.

What evidence suggests that D3L-001 might be an effective treatment for HER2-positive advanced solid tumors?

Research has shown that D3L-001 could effectively treat HER2-positive solid tumors. This treatment is a special antibody that targets both HER2 and CD47. In lab studies, D3L-001 demonstrated a strong ability to combat various tumors by aiding the immune system in attacking cancer cells. It works best on tumors with both HER2 and CD47 markers. This targeted approach may lead to better outcomes for individuals with these specific tumor types. Although these findings are preliminary, they offer hope for future treatment effectiveness. Participants in this trial will receive D3L-001 in different dose cohorts to evaluate its safety and efficacy. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 organs and bone marrow are working well.

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

I am fully active or can carry out light work.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• D3L-001

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

The study developed a bispecific antibody (CC-3) that targets B7-H3, which is overexpressed in colorectal cancer, showing enhanced tumor cell killing and T cell activation while minimizing unwanted cytokine release.

In animal models, CC-3 demonstrated strong antitumor effects, including preventing metastasis and eliminating large tumors, and is now moving towards clinical trials for evaluation in humans with colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An optimized IgG-based B7-H3xCD3 bispecific antibody for treatment of gastrointestinal cancers. Zekri, L., Lutz, M., Prakash, N., et al.[2023]

The bispecific F(ab')2 antibodies developed can effectively target and kill HER2-overexpressing tumor cells using activated T-lymphocytes, showing a strong binding affinity with a Kd of 2.49 nM even after 5 weeks in culture.

These antibodies not only localized to tumor xenografts in mice but also inhibited the growth of breast tumor cells in vitro, suggesting potential for effective cancer treatment strategies.

NCBI (Pubmed)

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. Shalaby, MR., Carter, P., Maneval, D., et al.[2019]

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]

IBI322, a bispecific antibody targeting both CD47 and PD-L1, effectively inhibits the 'do not eat me' signal in tumor cells while minimizing toxicity to red blood cells, making it a promising candidate for cancer immunotherapy.

In preclinical studies, IBI322 demonstrated strong tumor cell phagocytosis and significant tumor regression in vivo, with good tolerance observed in non-human primates, indicating a favorable safety profile for future clinical trials.

NCBI (Pubmed)

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. Wang, Y., Ni, H., Zhou, S., et al.[2021]

CD47-blocking bispecific antibodies (biAbs) effectively inhibit tumor growth and promote durable antitumor responses in a mouse model, even in the presence of the CD47 antigen sink.

The efficacy of these biAbs can be enhanced when used in combination with chemotherapy or PD-1/PD-L1 immune checkpoint inhibitors, suggesting a promising strategy for improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity. Dheilly, E., Majocchi, S., Moine, V., et al.[2020]

RTX-CD47 is a novel bispecific antibody designed to inhibit the CD47-SIRPα immune checkpoint specifically on cancer cells, potentially enhancing antitumor immunity.

This bispecific antibody works by binding to both CD47 and another target, effectively blocking the 'Don't eat me' signal that cancer cells use to evade the immune system, which could improve therapeutic outcomes in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Bispecific Antibody Derivatives for Cancer Immunotherapy. He, Y., Helfrich, W., Bremer, E.[2019]

CD3-bispecific antibodies are effective for treating some blood cancers but face significant challenges when used for solid tumors, including higher risks of side effects and difficulties in T-cell activation due to the tumor environment.

The review discusses potential combination strategies that could enhance the effectiveness and safety of CD3-bispecific antibody therapy in solid tumors, aiming to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors. Middelburg, J., Kemper, K., Engelberts, P., et al.[2023]

Bispecific antibodies are being developed to enhance the immune response against specific cancers and infectious diseases, showing promising results in early clinical trials with some patients experiencing complete or partial responses.

These antibodies work by linking a targeting domain that binds to tumors with a triggering arm that activates immune cells, potentially leading to a stronger immune attack and even a vaccine-like response in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies for the treatment of tumours and infectious diseases. Drakeman, DL., Fanger, MW., Wallace, PK.[2019]

The study developed four types of bispecific antibodies (bsAbs) that effectively redirect T cells to target and kill Her2-expressing cancer cells, including those with low Her2 expression, in both lab tests and rodent models.

While varying the valency of the bsAbs did not impact their effectiveness, having an Fc domain increased their cytotoxic activity but also led to unintended T-cell activation, highlighting the need to balance efficacy and safety in therapeutic design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiformat T-cell-engaging bispecific antibodies targeting human breast cancers. Cao, Y., Axup, JY., Ma, JS., et al.[2018]

Citations

1. withpower.com withpower.com/trial/phase-1-neoplasms-7-2023-5cd0d

D3L-001 for 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 ...

2. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/1873/719813/Abstract-1873-D3L-001-a-novel-bispecific-antibody

Abstract 1873: D3L-001, a novel bispecific antibody targeting ... D3L-001, a novel HER2×CD47 bsAb, demonstrated potent anti-tumor effect in a variety of solid tumor models via HER2 guided CD47 co-blocking.

3. researchgate.net researchgate.net/publication/369812523_Abstract_1873_D3L-001_a_novel_bispecific_antibody_targeting_HER2_and_CD47_demonstrates_potent_preclinical_efficacy_in_solid_tumors

D3L-001, a novel bispecific antibody targeting HER2 and CD47 ... With this unique design, D3L-001 showed preferential binding to HER2/CD47 double positive tumor cells as compared to CD47 single positive cells. D3L-001 showed ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-cd47-anti-her2-bispecific-antibody-d3l-001?pn=1

Clinical Trials Using Anti-CD47/Anti-HER2 Bispecific ... Review the clinical trials studying anti-cd47/anti-her2 bispecific antibody d3l-001 on this list and use the filters to refine the results by age and ...

5. researchgate.net researchgate.net/publication/385556877_626_A_phase_1_dose_escalation_and_expansion_study_evaluating_the_safety_tolerability_PK_PD_and_preliminary_efficacy_of_D3L-001_monotherapy_in_subjects_with_HER2_advanced_solid_tumors

626 A phase 1, dose escalation and expansion study ... D3L-001, a novel bispecific antibody targeting HER2 and CD47, demonstrates potent preclinical efficacy in solid tumors. AACR 2023; Abstract ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11772969/

Therapeutic strategies targeting CD47-SIRPα signaling ... Abstract 1873: D3L-001, a novel bispecific antibody targeting HER2 and CD47, demonstrates potent preclinical efficacy in solid tumors. Cancer Res. 2023;83 ...