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

Phase 1
Terminated
Conditions
cKIT-positive Solid Tumors
AML
Interventions
Registration Number
NCT02221505
Lead Sponsor
Novartis Pharmaceuticals
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
3
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

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LOP628 - Solid TumorLOP628with LOP628
LOP628 - AMLLOP628With LOP628
LOP628 - Solid Tumor ExpansionLOP628With LOP628
Primary Outcome Measures
NameTimeMethod
Incident rate of dose limiting toxicities (DLTs)Month 12

To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE)

Secondary Outcome Measures
NameTimeMethod
Best overall response (BOR)30 months

To assess the preliminary anti-tumor activity of LOP628 in patients

Best Overall Response (AML)30 months

To assess the preliminary anti-tumor activity of LOP628

Duration of response (DOR) (AML)30 months

To assess the preliminary anti-tumor activity of LOP628

Event Free Survival (EFS) (AML)30 months

To assess the preliminary anti-tumor activity of LOP628

Incidence of adverse events (AEs) and serious adverse events (SAE)30 months

Characterize the safety and tolerability of LOP628

Severity of adverse events (AEs) and serious adverse events (SAEs)30 months

Characterize the safety and tolerability of LOP628

Serum PK parameters (AUC, Cmax, Tmax, and half-life)30 months

To characterize the pharmacokinetic profile of LOP628

Serum concentration vs. time profiles30 months

To characterize the pharmacokinetic profile of LOP628.

Overall response rate (ORR)30 months

To assess the preliminary anti-tumor activity of LOP628

Duration of response (DOR)30 months

To assess the preliminary anti-tumor activity of LOP628

Progression Free Survival (PFS)30 months

To assess the preliminary anti-tumor activity of LOP628

Disease Control Rate (DCR) at 4 months4 months

To assess the preliminary anti-tumor activity of LOP628

Trial Locations

Locations (1)

Novartis Investigative Site

🇪🇸

Barcelona, Catalunya, Spain

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