Colorectal Cancer, Gastric Cancer, Locally Advanced or Metastatic Solid Tumors, Pancreatic Cancer
Conditions
Keywords
MRG007, Advanced or Metastatic Solid Tumors, CDH17, ARR-217, ADC
Brief summary
This is an open-label, multi-center, phase I study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of MRG007 (ARR-217) in patients with unresectable locally advanced or metastatic solid tumors.
Interventions
DRUGMRG007
MRG007 will be administrated as specified in the protocol.
DRUGMRG007 and Bevacizumab
MRG007 will be administered as specified in the protocol
Sponsors
ArriVent BioPharma, Inc.
Lepu Biopharma Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing to sign the informed consent form and follow the requirements specified in the protocol. 2. Life expectancy ≥ 3 months. 3. Tumor specimen available for CDH17 testing, or agree to biopsy at baseline. 4. Patients with histologically and cytologically confirmed advanced or metastatic solid tumor who have failed or intolerant to standard therapy, or without alternative standard therapy. 5. Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). 6. The score of ECOG for performance status is 0 or 1. 7. Organ functions and coagulation function must meet the basic requirements. 8. Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.
Exclusion criteria
1. Patients with more than one cancer. 2. Received CDH17-targeting anti-tumor therapy; received other investigational product, systemic corticosteroids or surgery for major organs within 4 weeks prior to the first dose; received anti-tumor therapy within 3 weeks or within 5 half-lives prior to the first dose, whichever is shorter; received radiotherapy within 2 weeks prior to the first dose; received strong CYP3A4 inducers or inhibitors within 2 weeks prior to the first dose or 5 half-lives, whichever is longer; investigational therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose. 3. ≥Grade 2 toxic reaction or abnormal value of laboratory test caused by previous anti-tumor treatment 4. Symptomatic Central nervous system and/or meninges metastasis. 5. History of severe cardiovascular diseases 6. Cerebrovascular accident, pulmonary embolism, or deep venous thrombosis within 3 months prior to the first dose, implantable venous infusion port or catheter-related thrombosis, or superficial venous thrombosis 7. History of previous or combined interstitial pneumonia, current interstitial pneumonia, or suspected interstitial pneumonia that cannot be ruled out through imaging during screening, severe chronic obstructive pulmonary disease with respiratory failure, severe pulmonary dysfunction, symptomatic bronchospasm, etc. 8. Poorly controlled pleural, peritoneal, and pelvic effusion, or combined pericardial effusion 9. Infection of active hepatitis B, active hepatitis C, or HIV 10. Uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infections requiring intravenous anti-infection therapy within 2 weeks prior to the first study treatment 11. Known allergic reactions to any component of MRG007, or known Grade≥3 allergic reactions to other prior anti-CDH17 (including investigational) or other monoclonal antibody. 12. Other situations that are not suitable to participate a clinical trial per investigator's judgement 13. Additional protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Related Adverse Event | Baseline to 30 days after the last dose of study treatment | Any reaction, side effect, or untoward event that occurs during the course of the clinical trial is considered related to the study drug. |
| Objective Response Rate (ORR) as assessed by investigator - Phase Ib | Baseline to study completion (up to 24 months) | ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed according to RECIST v1.1. |
| Dose Limiting Toxicity (DLT) - Phase Ia | Baseline to Day 21 of the first treatment cycle | — |
| Serious Adverse Events (SAEs) | Baseline to 30 days after the last dose of study treatment | Adverse events that are fatal, life-threatening, or result in hospitalization or prolonged hospitalization, persistent or significant disability/incapacity/substantial disruption of the ability to lead a normal life, congenital anomaly/birth defect or major medical events or reactions |
| Treatment-Emergent Adverse Event (TEAE) | Baseline to 30 days after the last dose of study treatment | AEs that occur or worsen on or after the first dose of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as assessed by investigator | Baseline to study completion (up to 24 months) | PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause. |
| Overall Survival (OS) | Baseline to study completion (up to 24 months) | OS is defined as the duration from the start of treatment to death of any cause. |
| Incidence of anti-drug antibody (ADA) | Baseline to 30 days after the last dose. | The proportion of patients with positive ADA results. |
| Incidence of neutralizing antibody (NAb) | Baseline to 30 days after the last dose. | The proportion of patients with positive NAb results. |
| Tmax | Baseline to 30 days after the last dose of study treatment | Time to reach the maximum blood concentration |
| Cmax | Baseline to 30 days after the last dose of study treatment | Maximum observed blood concentration |
| AUC0-t | Baseline to 30 days after the last dose of study treatment | Area under the blood concentration-time curve from time 0 to the time of last quantifiable concentration |
| QTc interval | Baseline to 30 days after the last dose of study treatment | Serum concentrations of MRG007, TAb, and unconjugated payload and change in QT interval corrected by Fridericia's formula (ΔQTcF) interval. |
| Objective Response Rate (ORR) - Phase Ia | Baseline to study completion (up to 24 months) | ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed according to RECIST v1.1. |
| Disease Control Rate (DCR) | Baseline to study completion (up to 24 months) | DCR is defined as the proportion of subjects achieving CR, PR, and stable disease (SD) after treatment. |
| Duration of Response (DOR) | Baseline to study completion (up to 24 months) | The time interval between the date of the earliest qualifying response and the date of disease progression or death for any cause, whichever occurs earlier. |
Countries
China, United States
Contacts
CONTACTClinical Trials
Outcome results
None listed