Phase 1 Study of LOP628 in Adult Patients With cKit-positive Solid Tumors and Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of LOP628, Administered Intravenously in Adult Patients With cKit-positive Tumors and Acute Myeloid Leukemia

Conditions
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AML, cKIT-positive Solid Tumors

Intervention / Treatment
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* Drug: LOP628


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LOP628 - Solid Tumor<br>with LOP628 | Drug: LOP628<br> <br> |
| Experimental: LOP628 - AML<br>With LOP628 | Drug: LOP628<br> <br> |
| Experimental: LOP628 - Solid Tumor Expansion<br>With LOP628 | Drug: LOP628<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incident rate of dose limiting toxicities (DLTs) | To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE) | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) and serious adverse events (SAE) | Characterize the safety and tolerability of LOP628 | 30 months | 
| Severity of adverse events (AEs) and serious adverse events (SAEs) | Characterize the safety and tolerability of LOP628 | 30 months | 
| Serum PK parameters (AUC, Cmax, Tmax, and half-life) | To characterize the pharmacokinetic profile of LOP628 | 30 months | 
| Serum concentration vs. time profiles | To characterize the pharmacokinetic profile of LOP628. | 30 months | 
| Overall response rate (ORR) | To assess the preliminary anti-tumor activity of LOP628 | 30 months | 
| Duration of response (DOR) | To assess the preliminary anti-tumor activity of LOP628 | 30 months | 
| Progression Free Survival (PFS) | To assess the preliminary anti-tumor activity of LOP628 | 30 months | 
| Disease Control Rate (DCR) at 4 months | To assess the preliminary anti-tumor activity of LOP628 | 4 months | 
| Best overall response (BOR) | To assess the preliminary anti-tumor activity of LOP628 in patients | 30 months | 
| Best Overall Response (AML) | To assess the preliminary anti-tumor activity of LOP628 | 30 months | 
| Duration of response (DOR) (AML) | To assess the preliminary anti-tumor activity of LOP628 | 30 months | 
| Event Free Survival (EFS) (AML) | To assess the preliminary anti-tumor activity of LOP628 | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LOP628,, cKit,, ADC,, Antibody drug conjugates,, maytansine