Testing DM005 for advanced solid tumors

A Phase 1, Multicenter, Open-label, First-in-human, Dose Escalation and Expansion Study of DM005 in Patients With Advanced Solid Tumors

This study is testing a new treatment called DM005 to see if it can help people with advanced solid tumors feel better and improve their health.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 136 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Doma Biopharmaceutical（Suzhou）Co., Ltd. (industry)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 6 sites (Detroit, Michigan and 5 other locations)
• Trial ID: NCT06515990 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, efficacy, and tolerability of DM005, an experimental bispecific antibody-drug conjugate, in patients with advanced solid tumors. Participants will undergo a screening period followed by treatment cycles where DM005 is administered intravenously. The study is designed as a first-in-human, multicenter, open-label trial with dose escalation and expansion phases to assess the drug's pharmacokinetics and preliminary efficacy. Patients will be monitored for infusion-related reactions and overall response to the treatment.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced non-small cell lung cancer, squamous cell carcinoma of the head and neck, or other solid tumors who have progressed on standard therapies.

Not a fit: Patients with another active invasive malignancy or those who are not eligible due to specific exclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have not responded to standard therapies.

How similar studies have performed: While this approach is novel, similar studies involving bispecific antibody-drug conjugates have shown promise in treating various cancers.

Eligibility criteria

Inclusion Criteria:

* Common inclusion criteria for both Parts

  1. Participants must have the ability to understand and willingness to sign a written informed consent document.
  2. Participants who have pathologically or cytologically documented metastatic/advanced NSCLC, gastroesophageal cancer, CRC, HCC, pancreatic cancer, or HNSCC, not curable with standard local therapies (i.e., surgery and/or radiation) and have progressed on standard therapy, or intolerant to standard therapy.
  3. Participants must be ≥18 years of age on the day of signing the informed consent form (ICF).
  4. Participants must have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2.
  5. Has a life expectancy ≥3 months.
  6. Has measurable disease based on response evaluation criteria in solid tumors (RECIST) version 1.1.

Exclusion Criteria:

* Participants are excluded from the study if any of the following criteria apply:

  1. Participants have another active invasive malignancy within 5 years, with the following exceptions and notes:

     * History of noninvasive malignancy, such as cervical cancer in situ, in situ melanoma, or ductal carcinoma in situ of the breast that is in complete remission years after treatment with curative intent is allowed.
     * Malignancies with a negligible risk of metastasis or death (such as adequately treated basal or squamous cell skin cancer and localized prostate cancer).
  2. Current or history of hematologic malignancy.
  3. Anticancer therapy (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or other anti-cancer therapies, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogs, agonists required to suppress serum testosterone levels) within 28 days or 5 half-lives, whichever is shorter, prior to the first study dose. Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days of the first study dose. Major surgery, other than diagnostic surgery, within 4 weeks of the first study dose.
  4. Primary central nervous system (CNS) malignancies or CNS metastases. Individuals with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (\>20 mg prednisone or equivalent) for at least 4 weeks.
  5. Presence of bulky disease (defined as any single mass \>7 cm in its greatest dimension). Individuals with a mass \>7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.
  6. Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
  7. Has clinically significant corneal disease.
  8. Has a corrected QT interval (QTcF) prolongation to \>470 ms (for both genders) based on average of the Screening triplicate 12-lead ECG determinations; no concomitant medications that would prolong the QT interval; no known family history of long QT syndrome.
  9. Left ventricular ejection fraction (LVEF) \<50% by either an echocardiogram (ECHO) or a multigated acquisition (MUGA) scan within 28 days before first dose of the study drug.
  10. Known active hepatitis B (HBV) or hepatitis C (HCV) infection. Chronic carriers of HBV infection (HBsAg-positive, undetectable HBV DNA or HBV DNA ≤2500 copies/ml or 500 IU/ml) receive prophylactic treatment during the study can be enrolled. Participants with a history of HCV infection have completed curative antiviral treatment and HCV viral load below the limit of quantification and HCV antibody positive but HCV ribonucleic acid (RNA) negative due to prior treatment or natural resolution should be eligible.
  11. Known human immunodeficiency virus (HIV) infection which is not well controlled. participants should be tested for HIV prior to enrollment if required by local regulations or institutional review board (IRB)/ethics committee. All the following criteria are required to define an HIV infection (positive HIV1/2 antibodies test) that is well controlled: HIV viral load \<400 copies/mL, CD4+ T-cell counts ≥350 cells/μL, no history of acquired immunodeficiency syndrome \[AIDS\])-defining opportunistic infection within the past 12 months, and stable viral load for at least 4 weeks on same anti-HIV retroviral medications.
  12. Participants from endemic area will be specifically screened for tuberculosis. Participants with active tuberculosis are excluded. Participants who have received bacille Calmette-Guerin (BCG) vaccination may have a false positive result in the purified protein derivative (PPD) skin test. These participants are eligible if they have a negative Interferon Gamma Release Assay (IGRA).
  13. Has received a live vaccine within 30 days prior to the first dose of study drug.
  14. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia and anemia) not yet resolved to NCI-CTCAE version 5.0, ≤Grade 1 or baseline. Note: Participants may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \>Grade 2 for at least 3 months prior to enrollment/randomization and managed with the standard treatment) that the Investigator deems related to previous anticancer therapy, following discussion with the Sponsor's medical monitor, such as the following: Grade 2 chemotherapy-induced neuropathy, hypothyroidism, hyperglycemia.
  15. Females who are pregnant or lactating or who intend to become pregnant during participation in the study.
  16. Participants who are of reproductive potential refuse to use effective methods of birth control during participation of the study and within 7 months for female (and 4 months for male) after the last dose administration.

Where this trial is running

Detroit, Michigan and 5 other locations

• Henry Ford Cancer Institute — Detroit, Michigan, United States (RECRUITING)
• Sarah Cannon Research Institute at Mary Crowley — Dallas, Texas, United States (RECRUITING)
• NEXT Oncology Virginia — Fairfax, Virginia, United States (RECRUITING)
• Chris O'Brien Lifehouse — Camperdown, New South Wales, Australia (RECRUITING)
• Macquarie University Hospital — North Ryde, New South Wales, Australia (RECRUITING)
• ICON Cancer Center — South Brisbane, Queensland, Australia (RECRUITING)

Study contacts

• Study coordinator: Wenjun Yu

Conditions: Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Solid Carcinoma