Clinical trial NCT06475937: A Study of DM001 in Patients With Advanced Solid Tumors
Official title: A Phase I, Multicenter, Open-label, First-in-Human, Dose Escalation and Expansion Study of DM001 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Solid Carcinoma
Lead sponsor: Doma Biopharmaceutical（Suzhou）Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-06-26
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This is a Phase 1, multicenter, openlabel, first-in-human (FIH), doseescalation and dose expansion study to evaluate the safety, tolerability, PK, and preliminary efficacy of DM001 in subjects with advanced solid tumors.

DM001, a bispecific ADC developed using fully human antibodies with a common light chain, which targets TROP2 and EGFR.

DM001 is sterile yellowish-green lyophilized powder for IV infusion.

Subjects with solid malignant tumors will be treated with DM001 on Day 1 once Q3W (dose adjustments may be required depending on the safety profile and PK data of each dose).

Eligibility criteria: Inclusion Criteria:

1. Subjects must have the ability to understand and willingness to sign a written informed consent document.
2. Subjects who have pathologically or cytologically confirmed documented metastatic/advanced breast cancer, EGFRmut or EGFRwt NSCLC, gastric cancer, gastroesophageal cancer or CRC, and have progressed on standard therapy, or intolerant to standard therapy, or no standard therapy accessible to the subjects due to any reason.
3. Subjects must be ≥18 years of age at the time of signing the informed consent form.
4. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Has a life expectancy of ≥3 months.
6. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Exclusion Criteria:

1. Subjects have another active invasive malignancy within 5 years.
2. Current or history of a hematologic malignancy.
3. Primary central nervous system (CNS) malignancies or CNS metastases. Individuals with brain metastases can be enrolled only if treated, nonprogressive brain metastases and off high-dose steroids (\>20 mg prednisone or equivalent) for at least 4 weeks.
4. Individuals with Gilbert's disease with ≥3 × ULN.
5. Has an uncontrolled infection requiring intravenous (IV) injection of antibiotics, antivirals, or antifungals.
6. Has a medical history of clinically significant lung diseases or is suspected to have these diseases by imaging at the screening period.
7. Clinically uncontrolled intercurrent illness, including but not limit to an ongoing active infection, active coagulopathy, uncontrolled cardiovascular disease, uncontrolled immune disease, uncontrolled diabetes, uncontrolled pleural and peritoneal effusion, psychiatric illness that would limit compliance with the study requirements and other serious medical illnesses requiring systemic therapies.
8. Mean resting corrected QT interval corrected by Fridericia's formula (QTcF, QTcF=QT/\[RR\]1/3) \>470 msec obtained from triplicate 12-lead ECGs at baseline; no concomitant medications that would prolong the QT internal; no family history of long QT syndrome.
9. Known human immunodeficiency virus infection, or active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Chronic carriers of HBV infection (hepatitis B surface antigen-positive, undetectable, or low HBV DNA) who receive prophylactic treatment during the study can be enrolled. Subjects 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 RNA negative due to prior treatment or natural resolution should be eligible.
10. Females who are pregnant or lactating or who intend to become pregnant during participation in the study are not eligible to participate.
11. Subjects who are of reproductive potential refuse to use effective methods of birth control during the course of participation in the study and within 120 days for both women and men of the last dose are ineligible to participate in the study.

Primary outcomes:
measure: Dose-limiting Toxicities (DLTs) of DM001
timeFrame: 12 months
measure: Maximum tolerated dose (MTD) for DM001
timeFrame: 12 months
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUC(0-inf), ng*h/mL)
timeFrame: 12 months
measure: Maximum (peak) plasma concentration (Cmax, ng/mL)
timeFrame: 12 months
measure: Time to maximum (peak) concentration (Tmax, h)
timeFrame: 12 months
measure: Trough concentration (Ctrough, ng/mL)
timeFrame: 12 months
measure: Objective response rate (ORR)
timeFrame: 12 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI)
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: South Brisbane
country: Australia
facility: Icon Cancer Centre South Brisbane
state: Queensland
city: Southport
country: Australia
facility: Tasman Oncology Research
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
Study officials:
affiliation: Xadcera Biopharmaceutical (Suzhou) Co., Ltd.
name: Zhaorong Chen, CMO
role: STUDY_CHAIR
References: