DM001 for Cancer

Recruiting at 5 trial locations

Overseen By Xi Cheng

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Xadcera Biopharmaceutical (Suzhou) Co., Ltd.

Must not be taking: High-dose steroids

Disqualifiers: Active malignancy, CNS metastases, uncontrolled infection, others

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

Compensation: Varies

Number of Visits: 8

Duration: 12 months

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of an experimental drug, DM001, for individuals with advanced solid tumors such as breast, lung, stomach, or colon cancer. Participants will receive DM001 through an IV infusion to determine its potential in managing cancer or improving conditions. Ideal candidates are those who have not found success with standard treatments or cannot access them. Individuals with advanced cancer who have exhausted available treatments may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not be on medications that prolong the QT interval (a heart rhythm measure), so you may need to discuss your current medications with the trial team.

Is there any evidence suggesting that DM001 is likely to be safe for humans?

Research has shown that some patients who took DM001 experienced safety issues. In one study, a serious side effect called dose-limiting toxicity (DLT) appeared, meaning the side effect was severe enough to halt dose increases. These side effects included serious neurological issues like chemical meningitis and other severe reactions. This indicates that while DM001 is being tested, there is a risk of serious side effects.

As this is an early-phase trial, the main goal is to assess the safety of DM001 and its tolerability. Researchers are still gathering initial information on how people react to DM001 and what side effects might occur. Early trials are designed to closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

DM001 is unique because it offers a new approach for treating advanced or metastatic solid tumors by utilizing an intravenous infusion method. Unlike many existing treatments that target tumor growth through more traditional chemotherapy, DM001 may work differently by potentially engaging a novel mechanism of action specific to this compound. Researchers are excited about DM001 because it could provide more targeted treatment options with the possibility of improved outcomes for patients with challenging tumor types.

What evidence suggests that DM001 might be an effective treatment for advanced solid tumors?

Research has shown that DM001, a new drug under study in this trial, offers promising results for treating advanced solid tumors. In lab tests, DM001 performed better at higher doses across various cancer models. This drug is an antibody-drug conjugate (ADC), combining a drug with an antibody to target cancer cells more precisely. Although ADCs have significantly improved cancer treatment, issues like resistance, where cancer cells stop responding, still occur. Early studies suggest DM001 might effectively target and destroy tumor cells, but further research is needed to confirm these results in humans. ^{3 4 6 7 8}

Who Is on the Research Team?

Zhaorong Chen, CMO

Principal Investigator

Xadcera Biopharmaceutical (Suzhou) Co., Ltd.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain advanced solid tumors, including breast cancer and non-small cell lung cancer (NSCLC), who have not responded to standard treatments or can't receive them. Participants must understand the study and agree to join, have a life expectancy of at least 3 months, and be able to perform daily activities with minimal assistance (ECOG status of 0 or 1).

Inclusion Criteria

I am fully active or have some restrictions but can still care for myself.

My doctor expects me to live for at least 3 more months.

My cancer can be measured using specific criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

1 visit (in-person)

Treatment

Participants receive DM001 in 3-week cycles with varying visit frequencies

12 months

5 visits during Cycle 1, 3 visits during Cycles 2 and 3, 1 visit during subsequent cycles

End of Treatment

Participants have an End of Treatment visit 21 days (+ 7 days) after the last dose of study drug

3-4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days (± 7 days)

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• DM001

Trial Overview DM001, an experimental drug for treating advanced solid tumors, is being tested for safety and effectiveness. The treatment period consists of cycles lasting three weeks each. Patients will visit the clinic multiple times during these cycles for assessments.

How Is the Trial Designed?

Group I: DM001 administrated to subjects with advanced or metastatic solid tumors Experimental Treatment 1 Intervention

An IV infusion of DM001 will be administrated approximately 30-60 min on Day 1 once Q3W

Who Is Running the Clinical Trial?

Xadcera Biopharmaceutical (Suzhou) Co., Ltd.

Lead Sponsor

Trials

2

Recruited

290+

Published Research Related to This Trial

PD-L1 checkpoint inhibitors, like durvalumab, have shown significant efficacy in treating various solid tumors, including lung cancer and breast cancer, by suppressing tumor growth and improving patient survival.

While PD-L1 therapy is generally safe, it can cause adverse reactions such as pneumonitis and colitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab in Solid Tumors. Chen, M., Jiang, J., Chen, J., et al.[2023]

Neoadjuvant anti-PD-1/PD-L1 therapy showed promising efficacy, with a complete response rate of 56.9% in triple-negative breast cancer and a major response rate of 47.1% in lung cancer, based on a meta-analysis of 20 studies involving 828 patients.

The therapy was generally safe, with fatigue being the most common adverse event (27.2%), while febrile neutropenia was the most frequent high-grade adverse event (8.4%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of neoadjuvant anti-PD-1/PD-L1 utilization among different tumors. Li, Z., Wu, X., Zhao, Y., et al.[2021]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

Adjuvant therapy with PD-1/PD-L1 inhibitors significantly improves overall survival (OS) and disease-free survival (DFS) in cancer patients, based on a meta-analysis of six randomized controlled trials involving 4,436 participants.

While these treatments offer substantial survival benefits, they are also associated with a higher risk of severe treatment-related adverse events (≥ grade 3), indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. Mo, DC., Liang, ZY., Chen, L., et al.[2022]

The antibody-drug conjugate T-DM1 effectively encourages immune cells to enter HER2-positive breast tumors, which is crucial for fighting the cancer.

When T-DM1 is combined with checkpoint inhibitors that block CTLA-4 and PD-1, it significantly enhances treatment effectiveness, leading to the elimination of breast tumors in 95% of treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibitors Boost Power of Antibody-Drug Conjugate. [2019]

T-DM1 effectively induces cell death in HER2-positive breast cancer cell lines by blocking the cell cycle at the G2/M phase, demonstrating its potential as a therapeutic agent.

However, T-DM1 does not enhance the effectiveness of radiation therapy, as it does not increase radiosensitivity in these cancer cells, indicating that further in vivo studies are necessary to fully understand its interactions with radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro effects of Trastuzumab Emtansine (T-DM1) and concurrent irradiation on HER2-positive breast cancer cells. Mignot, F., Kirova, Y., Verrelle, P., et al.[2021]

The antibody-drug conjugate T-DM1 demonstrated greater effectiveness than trastuzumab in treating HER2-positive gastric cancer cell lines, particularly in N-87 and OE-19, and showed promising results in xenograft models with complete pathological responses in all OE-19 and half of N-87 tumors.

T-DM1 not only induced direct cancer cell death and abnormal cell division but also enhanced immune response through antibody-dependent cellular cytotoxicity (ADCC), suggesting it could be a viable treatment option for patients with trastuzumab-resistant HER2-positive gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Barok, M., Tanner, M., Köninki, K., et al.[2015]

In a first-in-human study involving 24 patients with advanced HER2-positive breast cancer, trastuzumab-DM1 (T-DM1) demonstrated substantial clinical activity, achieving a clinical benefit rate of 73% at the maximum-tolerated dose (MTD) of 3.6 mg/kg.

T-DM1 was associated with mild and reversible side effects, such as transient thrombocytopenia and fatigue, with no severe adverse events like significant nausea or cardiac issues, indicating a favorable safety profile for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. Krop, IE., Beeram, M., Modi, S., et al.[2022]

The addition of immune checkpoint inhibitors to chemotherapy does not significantly increase the risk of high-grade hematological toxicities like anemia, thrombocytopenia, or neutropenia, based on a meta-analysis of 11 studies.

However, the combination treatment does lead to a significantly higher risk of high-grade diarrhea, indicating a specific area of concern for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity patterns associated with chemotherapy/immune checkpoint inhibitor combinations: a meta-analysis. Abdel-Rahman, O.[2020]

In a study of 87 women with HER2-positive breast cancer and brain metastases treated with T-DM1, the overall response rate was 24.5%, indicating that T-DM1 is effective in this challenging patient population.

Despite its activity, patients with brain metastases had a median overall survival of only 14 months compared to 32 months for those without central nervous system involvement, highlighting the need for improved treatment strategies for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer. Fabi, A., Alesini, D., Valle, E., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06475937

A Study of DM001 in Patients With Advanced Solid Tumors The goal of this clinical trial is to find out about the safety, efficacy, and tolerability of DM001 for patients with the advanced solid tumors.

2. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A1268

1152 DM001: A novel bispecific ADC targeting TROP2 and ... In vivo, DM001 exhibited potent, dose-dependent efficacy in multiple cell line and patient-derived xenografts when compared to benchmarks.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12480482/

Antibody–drug conjugates in breast cancer: mechanisms of ... Although antibody–drug conjugates (ADCs) revolutionized cancer treatment, especially in breast cancer, resistance remains a major challenge.

4. healthscout.app healthscout.app/trial_match/view_trial/NCT06475937/

Trial: A Study of DM001 in Patients With Advan… - HealthScout The goal of this clinical trial is to find out about the safety, efficacy, and tolerability of DM001 for patients with the advanced solid tumors. DM001 is ...

5. facingourrisk.org facingourrisk.org/research-clinical-trials/results?amp%3Bstage=stage%204&amp%3Bstudy_type=treatment&cancer_type=breast&page=1

Research & Clinical Trials Search Results: Breast Cancer This study will look at how well a new oral targeted therapy known as an ATR inhibitor works on advanced or metastatic solid tumors with mutations in genes ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06475937

A Study of DM001 in Patients With Advanced Solid Tumors The goal of this clinical trial is to find out about the safety, efficacy, and tolerability of DM001 for patients with the advanced solid tumors.

7. ancora.ai ancora.ai/es/details/NCT06475937

A Study of DM001 in Patients With Advanced Solid Tumors The goal of this clinical trial is to find out about the safety, efficacy, and tolerability of DM001 for patients with the advanced solid tumors.

8. clin.larvol.com clin.larvol.com/trial-detail/NCT06475937

A Study of DM001 in Patients With Advanced Solid Tumors A dose-limiting toxicity (DLT) was defined as grade 3 neurological toxicities (e.g. chemical meningitis) or other grade 4 toxicity. 12 months. Maximum tolerated ...