Advanced Solid Tumor
Conditions
Brief summary
This study is a Phase 1 open-label, first-in-human, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and activity of KM602 as monotherapy in patients with advanced solid tumors.
Detailed description
This Phase 1 study is comprised of dose escalation and expansions for KM602 monotherapy. Monotherapy dose escalation is designed with initial accelerated titration followed by a standard 3+3 dose escalation; Patients will remain on study treatment until progression of disease, unacceptable toxicity, or other specified reason for discontinuation.
Interventions
BIOLOGICALKM602
Multiple dose levels of KM602 will be administered, including 0.01 mg/kg QW, 0.1 mg/kg QW, 0.6 mg/kg QW, 3 mg/kg QW, and 10 mg/kg QW. KM602 is administered intravenously once a week, and each cycle is 21 days.
Sponsors
Xuanzhu Biopharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed, disease that is unresectable, locally advanced, or metastatic and has progressed following all standard treatments or is not appropriate for standard treatments (predominantly melanoma and non-small cell lung cancer) 2. All patients must have at least one measurable lesion at baseline according to RECIST v1.1 3. ECOG performance status of 0 or 1 4. Life expectancy of ≥ 12 weeks 5. Adequate baseline hematologic, renal, and hepatic function
Exclusion criteria
1. Patients with meningeal metastasis or symptomatic central nervous system metastasis 2. Any second malignancy active within the previous 5 years 3. Any active, known, or suspected autoimmune disease 4. Active or prior pneumonitis or interstitial lung disease 5. Prior organ allograft or allogeneic hematopoietic stem cell transplantation 6. Treatment with any anti-cancer therapy or participation in another investigational drug or biologics trial within 4 weeks prior to the first dose of KM602 7. Prior treatment with a CTLA-4 antagonist, including ipilimumab and tremelimumab 8. History of ≥ Grade 3 immune-related adverse event leading to treatment discontinuation 9. Systemic treatment with corticosteroids (\> 10 mg/day prednisone) or other immunosuppressive medication within 14 days prior to the first dose of KM602 or during the study 10. Known seropositivity for or active infection by human immunodeficiency virus, hepatitis B or C 11. Known allergies, hypersensitivity, or intolerance to KM602 or excipients in the drug product formulation 12. Active infection requiring therapy at the time of the first dose of KM602 13. Pregnancy or breastfeeding 14. Any serious or uncontrolled health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study, impair the ability of the subject to receive protocol specified therapy, or interfere with the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) of KM602, if any | Approximately 15 months | Determined by the frequency of dose-limiting toxicities during dose-escalation |
| Recommended Phase 2 dose (RP2D) of KM602 | Approximately 15 months | Determined by the frequency of dose-limiting toxicities during dose-escalation |
| Incidence of treatment emergent adverse events | Through study completion, approximately 28 months | Severity graded per CTCAE version 5.0 |
Secondary
| Measure | Time frame |
|---|---|
| Volume of distribution (V) of KM602 | Through study completion, approximately 28 months |
| Maximum Plasma Concentration (Cmax) of KM602 | Through study completion, approximately 28 months |
| Area Under the Curve (AUC) of KM602 | Through study completion, approximately 28 months |
| t1/2 of KM602 | Through study completion, approximately 28 months |
| Objective Response Rate (ORR) of KM602 | Through study completion, approximately 28 months |
| Progression-free survival(PFS) of KM602 | Through study completion, approximately 28 months |
| Duration of Response (DOR) of KM602 | Through study completion, approximately 28 months |
| Overall survival (OS) of KM602 | Through study completion, approximately 28 months |
| Anti-Drug Antibody of KM602 | Through study completion, approximately 28 months |
| Disease Control Rate (DCR) of KM602 | Through study completion, approximately 28 months |
| Plasma clearance (CL) of KM602 | Through study completion, approximately 28 months |
Countries
China
Contacts
Primary ContactXingming Fan
Outcome results
None listed