Clinical trial NCT03667170: KN035 for dMMR/MSI-H Advanced Solid Tumors
Official title: Study of KN035 as Monotherapy in Patients With Advanced Mismatched Repair Deficient (dMMR) or Microsatellite Instability-High (MSI-H) Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Solid Tumor
Keywords: MSI-H
dMMR
Colorectal cancer
Non-Colorectal Cancers
Lead sponsor: 3D Medicines
Sponsor class: INDUSTRY
First posted: 2018-09-12
Enrollment: 200
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: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: ORR
timeFrame: Up to approximately 2 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital, Peking University
state: Beijing
Study officials:
affiliation: Peking Universtiy Cancer Hospital
name: Lin Shen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.