Treatment of Advanced and Metastatic Solid Tumors With MIL97

NCT04965077 | Recruiting Phase 1

• 1 other identifier: MIL97-CT101
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, global, multi-center, open-label, multiple-dose, first-in-human study of MIL97 to evaluate the safety, tolerability, pharmacokinetics, biomarkers and efficacy in subjects with advanced or metastatic solid tumor. The study consists of a dose escalation phase and a dose expansion phase. An accelerated titration design (cohorts 1-2 only) followed by 3+3 dose-escalation design will be used in dose escalation phase. The starting dose for dose escalation phase is 0.01 mg/kg Q3W, followed by 5 dose cohorts (0.03mg/kg Q3W, 0.1mg/kg Q3W, 0.2mg/kg Q3W, 0.3mg/kg Q3W and 0.45mg/kg Q3W). Duration of dose limiting toxicity (DLT) observation is 21 days. Based on data of 3-week treatment regimen, one or two dose levels may be chosen for Q2w regimen. Duration of dose limiting toxicity (DLT) observation is 28 days. One or two dose cohorts will be chosen (either 2-week regimen or 3-week regimen cohorts) to expand to total of 10 subjects in each cohort for further exploration of PK as well as safety and efficacy.

Conditions

Advanced or Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (1)

• The incidence of MIL97 treatment-emergent adverse events in patients with advanced or metastatic solid tumor

  incidence of AEs and SAEs assessed by NCI CTCAE v5.0.

  up to 2.5 year after enrollment

Secondary Outcomes (9)

• Pharmacokinetics: AUC

  up to 1.5 year after enrollment

• Pharmacokinetics: Cmax;

  up to 1.5 year after enrollment

• Objective response rate (ORR);

  up to 2.5 year after enrollment

• Duration of response (DoR);

  up to 2.5 year after enrollment

• Progression free survival (PFS);

  up to 2.5 year after enrollment

Study Arms (1)

MIL97

EXPERIMENTAL

Drug: Recombinant Humanized Monoclonal Antibody MIL97 for Injection

Interventions

Recombinant Humanized Monoclonal Antibody MIL97 for Injection DRUG

Dose escalation phase: The patients confirming to the eligibility criteria will be assigned to the 6 dose groups (0.01mg/kg, 0.03mg/kg, 0.1mg/kg, 0.2mg/kg, 0.3mg/kg 0.45mg/kg, respectively) based on the sequence of inclusion. Each patient will receive an intravenous infusion of MIL97 every 3 week on Day 1 of each cycle. Additional 1 or 2 dose cohorts will receive an intravenous infusion of MIL97 every 2 week on Day 1 of each cycle after last patient finishes DLT observation period. Dose expansion phase: One or two recommended expansion doses (either Q3W or Q2W) will be selected from 6 dose groups (0.01mg/kg, 0.03mg/kg, 0.1mg/kg, 0.2mg/kg, 0.3mg/kg 0.45mg/kg) based on results of dose escalation phase. MIL97 will be administered via intravenous infusion for 60 to 90 minutes on Day 1 of each cycle.

MIL97

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, \>=18 years of age;
• Diagnosis of Refractory/relapsed metastatic and/or unresectable solid tumors;
• At least one extracranial measurable unirradiated lesion or evaluable lesion (recist v1.1) ;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1Life expectancy \>=3 months;
• Sufficient organ and bone marrow function within 7 days before enrollment;
• Life expectancy \>=12 weeks;
• Able and willing to provide written informed consent and to comply with the study protocol.

You may not qualify if:

• have a history of myocardial infarction within 6 months or a history of arterial thromboembolic event within 3 months before the first dose;
• Comorbidity that would interfere with therapy, including interstitial pneumonia, symptomatic congestive heart failure; unstable angina, uncontrolled hypertension; ongoing cardiac arrhythmia ≥ CTCAE 5.0 Grade 3, active coagulopathy, uncontrolled diabetes, QTcF\>450ms (Male) or QTcF\>470ms (Female) at screening;
• Patients have a known or suspected history of an autoimmune disorder, except for the following: Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are eligible;
• Have a history of manifested central nervous system (CNS) metastases or have primary brain tumor. Patients with known or suspected leptomeningeal disease or cord compression;
• Receipt of allograft or allogeneic hematopoietic stem cell transplantation;
• Patients have another active invasive malignancy, but history of a non-invasive malignancy and history of malignancy that is in complete remission after treatment with curative intent are allowed;
• Active known clinically serious infections are required intravenous antibiotic treatment;
• Have a history of primary immunodeficiency, including but not limited with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness;
• Active and clinical significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C (HCV) (Hepatitis B should be confirmed as HBV surface antigen (HBsAg) positive or HBV core antibody (HBcAb) positive with HBV DNA above ULN);
• Any antitumor therapy within prior 4 weeks (including chemotherapy, targeted therapy, hormone therapy, immunotherapy, radiotherapy, tumor embolization, etc), except for palliative radiotherapy for relief bone pain;
• Major surgery within prior 4 weeks or expected to require major surgery during study treatment (Major surgery: laparotomy, thoracotomy, and internal organs excision by laparoscopic surgery);
• Patients have concurrent received or used an immunosuppressive agent within 14 days before study treatment, with the following exceptions and notes: Systemic steroids at physiologic doses, intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption, transient courses of steroids may be approved by the Medical Monitor;
• Previous exposure to CD40 antibodies;
• Patients received a live attenuated vaccine within 28 days before study treatment and plan to receive live vaccines during the study unless approved by both investigator and sponsor;
• Toxicities due to prior therapy are unresolved to ≤ CTCAE 5.0 Grade 1 except for AEs not constituting a safety risk to the patient based on the judgment of investigators;

Sponsors & Collaborators

• Beijing Mabworks Biotech Co., Ltd.: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Injections

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Jianming Xu, Ph.D

CONTACT

13910866712; jmxu2003@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 16, 2021
• Study Start: January 18, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 13, 2024

Record last verified: 2023-12

Locations

CN (1)