KN035 for dMMR/MSI-H Advanced Solid Tumors

Study of KN035 as Monotherapy in Patients With Advanced Mismatched Repair Deficient (dMMR) or Microsatellite Instability-High (MSI-H) Solid Tumors

In this study, patients with previously-treated locally-advanced or metastatic mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal carcinoma (CRC) and other solid tumors will be treated with KN035 monotherapy.

For colorectal cancer participants, who are required to have been previously treated with standard therapies , other solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Biological: KN035

Detailed Description

Later-line therapies after failure of standard treatments for advanced colorectal and non-colorectal cancer patients are limited. Mismatch repair (MMR) deficiency or microsatellite instability-high (MSI-H) played a role of positive predictive factor, which had been documented after the pembrolizumab and nivolumab trial were reported, for PD-1 blockade monotherapy in patients with advanced colorectal and non-colorectal cancers.

In this study, patients with previously-treated locally-advanced or metastatic mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal carcinoma (CRC) and other solid tumors will be treated with KN035 monotherapy.

For colorectal cancer participants, who are required to have been previously treated with standard therapies. For other solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lin Shen, MD; Phone Number: 86-10-88196340; Email: doctorshenlin@sina.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking University Cancer Hospital, Peking University
      • Contact: Lin Shen, MD; Phone Number: 86-010-88196340; Email: doctorshenlin@sina.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed locally advanced or metastatic colorectal carcinoma or other malignant solid tumors.
• Confirmed MMR deficient or MSI-H status.
• At least one measureable lesion.
• Eastern Cooperative Oncology Group performance status of 0 or 1 .
• Life expectancy of greater than 12 weeks.
• Adequate hematologic and organ function.

Exclusion Criteria:

• Currently participated in a study of an investigational agent and received trial treatment, or used an investigational device within 4 weeks of the first dose of medication in this study. Patients who have had specific anti-tumor treatment within 2 weeks prior to the first dose of study.
• Patients who have not recovered to CTCAE Grade 1 or better from related side effects of any prior antineoplastic therapy.
• Has received prior therapy with an immune check point agonist/inhibitor.
• Patients who have undergone major surgery within 4 weeks of dosing of investigational agent.
• Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Active autoimmune disease that has required systemic treatment.
• Patients who have known history of infection with HIV.
• Patients with evidence of interstitial lung disease.
• Patients who have known history of any major cardiac abnormalities.
• Patient who is not willing to apply highly effective contraception during the study.
• Patients who have other concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate patient participation in the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects with MSI-H/dMMR; patients receive 600 mg of the KN035 Subcutaneously every 3 weeks	Biological: KN035; subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	per RECIST 1.1 assessed by central imaging vendor and investigator	Up to approximately 2 years
Duration of Response (DOR)	per RECIST 1.1 assessed by central imaging vendor and investigator	Up to approximately 2 years
Progression-Free Survival (PFS)	per RECIST 1.1 assessed by central imaging vedor and investigator	Up to approximately 2 years
Overall Survival (OS)	Calculated by the Kaplan-Meier method.	Up to approximately 2 years
ORR	per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by investigator	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: 3D Medicines (Sichuan) Co., Ltd.
• Investigators: Principal Investigator: Lin Shen, MD, Peking Universtiy Cancer Hospital

Publications and helpful links

General Publications

• Li J, Deng Y, Zhang W, Zhou AP, Guo W, Yang J, Yuan Y, Zhu L, Qin S, Xiang S, Lu H, Gong J, Xu T, Liu D, Shen L. Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors. J Hematol Oncol. 2021 Jun 21;14(1):95. doi: 10.1186/s13045-021-01095-1.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2018
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 15, 2025

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Colorectal cancer; dMMR; MSI-H; Non-Colorectal Cancers
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: KN035-CN-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No