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

AML Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02221505
• Other study ID #: CLOP628X2101
• Status: Terminated
• Phase: Phase 1
• First received: August 8, 2014
• Last updated: April 2, 2016
• Start date: December 2014
• Est. completion date: March 2015

Study information

• Verified date: April 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• AML
• cKIT-positive Solid Tumors
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• LOP628

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Parkville	Victoria
Belgium	Novartis Investigative Site	Leuven
Netherlands	Novartis Investigative Site	Leiden
Spain	Novartis Investigative Site	Barcelona	Catalunya

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Belgium,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incident rate of dose limiting toxicities (DLTs)	To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE)	Month 12	Yes
Secondary	Incidence of adverse events (AEs) and serious adverse events (SAE)	Characterize the safety and tolerability of LOP628	30 months	Yes
Secondary	Severity of adverse events (AEs) and serious adverse events (SAEs)	Characterize the safety and tolerability of LOP628	30 months	Yes
Secondary	Serum PK parameters (AUC, Cmax, Tmax, and half-life)	To characterize the pharmacokinetic profile of LOP628	30 months	No
Secondary	Serum concentration vs. time profiles	To characterize the pharmacokinetic profile of LOP628.	30 months	No
Secondary	Overall response rate (ORR)	To assess the preliminary anti-tumor activity of LOP628	30 months	No
Secondary	Duration of response (DOR)	To assess the preliminary anti-tumor activity of LOP628	30 months	No
Secondary	Progression Free Survival (PFS)	To assess the preliminary anti-tumor activity of LOP628	30 months	No
Secondary	Disease Control Rate (DCR) at 4 months	To assess the preliminary anti-tumor activity of LOP628	4 months	No
Secondary	Best overall response (BOR)	To assess the preliminary anti-tumor activity of LOP628 in patients	30 months	No
Secondary	Best Overall Response (AML)	To assess the preliminary anti-tumor activity of LOP628	30 months	No
Secondary	Duration of response (DOR) (AML)	To assess the preliminary anti-tumor activity of LOP628	30 months	No
Secondary	Event Free Survival (EFS) (AML)	To assess the preliminary anti-tumor activity of LOP628	30 months	No