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

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

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.

Study Overview

• Status: Terminated
• Conditions: AML; cKIT-positive Solid Tumors
• Intervention / Treatment: Drug: LOP628

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Netherlands
  • Leiden, Netherlands, 2300 RC
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LOP628 - Solid Tumor; with LOP628	Drug: LOP628
Experimental: LOP628 - AML; With LOP628	Drug: LOP628
Experimental: LOP628 - Solid Tumor Expansion; With LOP628	Drug: LOP628

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: August 8, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 20, 2014

Study Record Updates

• Last Update Posted (Estimate): April 5, 2016
• Last Update Submitted That Met QC Criteria: April 2, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: maytansine; LOP628,; cKit,; ADC,; Antibody drug conjugates,
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: CLOP628X2101