Phase 1 Study of LOP628 in Adult Patients With cKit-positive Solid Tumors and Acute Myeloid Leukemia
Primary Purpose
cKIT-positive Solid Tumors, AML
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LOP628
Sponsored by
About this trial
This is an interventional treatment trial for cKIT-positive Solid Tumors focused on measuring LOP628,, cKit,, ADC,, Antibody drug conjugates,, maytansine
Eligibility Criteria
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
LOP628 - Solid Tumor
LOP628 - AML
LOP628 - Solid Tumor Expansion
Arm Description
with LOP628
With LOP628
With LOP628
Outcomes
Primary Outcome Measures
Incident rate of dose limiting toxicities (DLTs)
To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE)
Secondary Outcome Measures
Incidence of adverse events (AEs) and serious adverse events (SAE)
Characterize the safety and tolerability of LOP628
Severity of adverse events (AEs) and serious adverse events (SAEs)
Characterize the safety and tolerability of LOP628
Serum PK parameters (AUC, Cmax, Tmax, and half-life)
To characterize the pharmacokinetic profile of LOP628
Serum concentration vs. time profiles
To characterize the pharmacokinetic profile of LOP628.
Overall response rate (ORR)
To assess the preliminary anti-tumor activity of LOP628
Duration of response (DOR)
To assess the preliminary anti-tumor activity of LOP628
Progression Free Survival (PFS)
To assess the preliminary anti-tumor activity of LOP628
Disease Control Rate (DCR) at 4 months
To assess the preliminary anti-tumor activity of LOP628
Best overall response (BOR)
To assess the preliminary anti-tumor activity of LOP628 in patients
Best Overall Response (AML)
To assess the preliminary anti-tumor activity of LOP628
Duration of response (DOR) (AML)
To assess the preliminary anti-tumor activity of LOP628
Event Free Survival (EFS) (AML)
To assess the preliminary anti-tumor activity of LOP628
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02221505
Brief Title
Phase 1 Study of LOP628 in Adult Patients With cKit-positive Solid Tumors and Acute Myeloid Leukemia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Terminated
Study Start Date
December 2014 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
cKIT-positive Solid Tumors, AML
Keywords
LOP628,, cKit,, ADC,, Antibody drug conjugates,, maytansine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LOP628 - Solid Tumor
Arm Type
Experimental
Arm Description
with LOP628
Arm Title
LOP628 - AML
Arm Type
Experimental
Arm Description
With LOP628
Arm Title
LOP628 - Solid Tumor Expansion
Arm Type
Experimental
Arm Description
With LOP628
Intervention Type
Drug
Intervention Name(s)
LOP628
Primary Outcome Measure Information:
Title
Incident rate of dose limiting toxicities (DLTs)
Description
To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE)
Time Frame
Month 12
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AEs) and serious adverse events (SAE)
Description
Characterize the safety and tolerability of LOP628
Time Frame
30 months
Title
Severity of adverse events (AEs) and serious adverse events (SAEs)
Description
Characterize the safety and tolerability of LOP628
Time Frame
30 months
Title
Serum PK parameters (AUC, Cmax, Tmax, and half-life)
Description
To characterize the pharmacokinetic profile of LOP628
Time Frame
30 months
Title
Serum concentration vs. time profiles
Description
To characterize the pharmacokinetic profile of LOP628.
Time Frame
30 months
Title
Overall response rate (ORR)
Description
To assess the preliminary anti-tumor activity of LOP628
Time Frame
30 months
Title
Duration of response (DOR)
Description
To assess the preliminary anti-tumor activity of LOP628
Time Frame
30 months
Title
Progression Free Survival (PFS)
Description
To assess the preliminary anti-tumor activity of LOP628
Time Frame
30 months
Title
Disease Control Rate (DCR) at 4 months
Description
To assess the preliminary anti-tumor activity of LOP628
Time Frame
4 months
Title
Best overall response (BOR)
Description
To assess the preliminary anti-tumor activity of LOP628 in patients
Time Frame
30 months
Title
Best Overall Response (AML)
Description
To assess the preliminary anti-tumor activity of LOP628
Time Frame
30 months
Title
Duration of response (DOR) (AML)
Description
To assess the preliminary anti-tumor activity of LOP628
Time Frame
30 months
Title
Event Free Survival (EFS) (AML)
Description
To assess the preliminary anti-tumor activity of LOP628
Time Frame
30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
12. IPD Sharing Statement
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Phase 1 Study of LOP628 in Adult Patients With cKit-positive Solid Tumors and Acute Myeloid Leukemia
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