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

Trial Summary

What is the purpose of this trial?

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 an experimental drug which is not approved by health authorities for the treatment of advanced solid tumors. Participants will have up to 17 visits during the study.There will be up to a 4-week Screening Period followed by a treatment period that will be divided into 3-week cycles/ Participants will have 5 study visits during Cycle 1, 3 visits during Cycles 2 and 3, and 1 visit during subsequent cycles. Participants will have an End of Treatment visit 21 days (+ 7 days) after last dose of study drug and then a follow-up visit 30 days (± 7 days) after the End of Treatment visit.

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.

What safety data exists for DM001 (PD-L1 inhibitors) in humans?

PD-L1 inhibitors, like DM001, have been shown to be generally safe in many patients, but some people may experience side effects such as lung inflammation, liver inflammation, colon inflammation, nerve problems, and heart inflammation. These treatments have been used in various cancers, and while they are mostly safe, it's important to be aware of these potential adverse reactions. ^{1 2 3 4 5}

How is the drug DM001 different from other cancer treatments?

DM001 is an antibody-drug conjugate that combines trastuzumab with the drug DM1 to specifically target and deliver treatment to HER2-positive cancer cells, which is different from traditional chemotherapy that affects both cancerous and healthy cells. ^{6 7 8 9 10}

Research Team

Zhaorong Chen, CMO

Principal Investigator

Xadcera Biopharmaceutical (Suzhou) Co., Ltd.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab in Solid Tumors. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Clinical benefit of neoadjuvant anti-PD-1/PD-L1 utilization among different tumors. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

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

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

7. United States 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. [2022]

8. France pubmed.ncbi.nlm.nih.gov

In vitro effects of Trastuzumab Emtansine (T-DM1) and concurrent irradiation on HER2-positive breast cancer cells. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer. [2019]

10. Ireland pubmed.ncbi.nlm.nih.gov

Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. [2015]