Clinical trial NCT02221505: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: cKIT-positive Solid Tumors
AML
Keywords: LOP628,
cKit,
ADC,
Antibody drug conjugates,
maytansine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-08-20
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incident rate of dose limiting toxicities (DLTs)
timeFrame: Month 12
Secondary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAE)
timeFrame: 30 months
measure: Severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 30 months
measure: Serum PK parameters (AUC, Cmax, Tmax, and half-life)
timeFrame: 30 months
measure: Serum concentration vs. time profiles
timeFrame: 30 months
measure: Overall response rate (ORR)
timeFrame: 30 months
measure: Duration of response (DOR)
timeFrame: 30 months
measure: Progression Free Survival (PFS)
timeFrame: 30 months
measure: Disease Control Rate (DCR) at 4 months
timeFrame: 4 months
measure: Best overall response (BOR)
timeFrame: 30 months
measure: Best Overall Response (AML)
timeFrame: 30 months
measure: Duration of response (DOR) (AML)
timeFrame: 30 months
measure: Event Free Survival (EFS) (AML)
timeFrame: 30 months
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: