AML, cKIT-positive Solid Tumors
Conditions
Keywords
LOP628,, cKit,, ADC,, Antibody drug conjugates,, maytansine
Brief summary
LOP628 is an antibody-drug conjugate (ADC) consisting of an anti-cKit humanized IgG1/κ antibody conjugated to a maytansine payload via a non-cleavable linker. LOP628 provides an opportunity to target cKit overexpressing tumors.
Interventions
DRUGLOP628
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For patients with solid tumors: * documented cKit-positive neoplasms * Patient must have progressive disease as defined by any of the following: * SCLC: patient has progressed after at least 1 prior therapy * GIST : patient has relapsed or has refractory disease, and no further approved effective therapeutic option exists * Patients with other cKit-positive solid tumors: patient has progressed after at least one prior line of therapy and no further approved effective therapeutic option exists * Patient has measurable disease as per RECIST v1.1 criteria For patients with AML: * documented cKit-positive acute myelogenous leukemia * Consent to newly obtained bone marrow aspirate * Patient must have progressive disease defined as relapsed or refractory non-PML AML following standard therapy or for whom no effective therapy exists. * Blast count \< 50,000/mm3
Exclusion criteria
For patients with solid tumors: * Patient has central nervous system (CNS) metastatic involvement unless the CNS metastases have been previously treated and the patient is clinically stable and on a stable dose of corticosteroids for at least 4 weeks prior to enrollment. * Patient has the presence of other clinically significant hematologic, cardiac, respiratory, gastrointestinal, renal, hepatic or neurological conditions. * Patient has a history of serious allergic reactions, which in the opinion of the investigator may pose an increased risk of serious infusion reactions * Patient has been previously treated with cKit directed antibodies * Pregnant or nursing women For patients with AML: * Patient has received prior allogeneic bone marrow transplant (BMT). * Patient has the presence of other clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic or neurological disease * Patient has a history of serious allergic reactions, which in the opinion of the investigator may pose an increased risk of serious infusion reactions * Patient has been previously treated with cKit directed antibodies * Pregnant or nursing women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incident rate of dose limiting toxicities (DLTs) | Month 12 | To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAE) | 30 months | Characterize the safety and tolerability of LOP628 |
| Serum PK parameters (AUC, Cmax, Tmax, and half-life) | 30 months | To characterize the pharmacokinetic profile of LOP628 |
| Serum concentration vs. time profiles | 30 months | To characterize the pharmacokinetic profile of LOP628. |
| Overall response rate (ORR) | 30 months | To assess the preliminary anti-tumor activity of LOP628 |
| Duration of response (DOR) | 30 months | To assess the preliminary anti-tumor activity of LOP628 |
| Severity of adverse events (AEs) and serious adverse events (SAEs) | 30 months | Characterize the safety and tolerability of LOP628 |
| Disease Control Rate (DCR) at 4 months | 4 months | To assess the preliminary anti-tumor activity of LOP628 |
| Best overall response (BOR) | 30 months | To assess the preliminary anti-tumor activity of LOP628 in patients |
| Best Overall Response (AML) | 30 months | To assess the preliminary anti-tumor activity of LOP628 |
| Duration of response (DOR) (AML) | 30 months | To assess the preliminary anti-tumor activity of LOP628 |
| Event Free Survival (EFS) (AML) | 30 months | To assess the preliminary anti-tumor activity of LOP628 |
| Progression Free Survival (PFS) | 30 months | To assess the preliminary anti-tumor activity of LOP628 |
Countries
Australia, Belgium, Netherlands, Spain
Outcome results
None listed