This is a multicenter, open-label, single-arm study to investigate the safety, tolerability, PK, pharmacodynamics and preliminary activity of INCA32459 in participants with selected advanced malignancies. Part 1 (dose escalation) will determine the recommended dose of INCA 32459 for expansion (RDE) and the maximum tolerated dose (MTD). Part 2 (dose expansion) will further evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of INCA 32459 at the recommended dose(s) for expansion in 2 tumor-specific cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
solution for infusion
The Angeles Clinic and Research Institute
Los Angeles, California, United States
University of Texas Md Anderson Cancer Center
Houston, Texas, United States
Cliniques Universitaires Ucl Saint-Luc
Brussels, Belgium
Part 1: Occurrence of Dose Limiting Toxicities (DLTs)
Toxicities occurring during Part 1 will define tolerability. DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria.
Time frame: Up to approximately 12 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Time frame: Up to approximately 12 months
Number of Participants with Dose Interruptions due to TEAE
Dose interruptions will occur according to protocol guidelines.
Time frame: Up to approximately 12 months
Number of Participants discontinue study due to TEAE
TEAE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to approximately 12 months
Objective Response Rate (ORR)
Defined as having Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or Lugano criteria (B-cell lymphomas only).
Time frame: Up to 12 months
Disease Control Response (DCR)
Defined as having CR, PR, or Stable Disease (SD) as determined by the investigator by radiographic disease assessment according to RECIST v1.1. or Lugano criteria (B-cell lymphomas only).
Time frame: Up to 12 months
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Universitair Ziekenhuis Antwerpen (Uza)
Edegem, Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium
Universitair Ziekenhuis Brussel
Jette, Belgium
Chu Ucl Namur University Hospital Mont-Godinne
Yvoir, Belgium
Centro Ricerche Cliniche Di Verona (Crc)
Verona, Italy
Hospital Quironsalud Barcelona
Barcelona, Spain
Ico Institut Catala D Oncologia
L'Hospitalet de Llobregat, Spain
...and 3 more locations
Duration of Response (DOR)
Defined as the time from earliest date of disease response (Completed Response or Partial Response) until earliest date of disease progression as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or Lugano criteria (B-cell lymphomas only) or death due to any cause if occurring sooner than progression.
Time frame: Up to 12 months
PK parameters: Cmax
Defined as the maximum (peak) plasma drug concentration
Time frame: Up to 24 months
PK parameters: tmax
Defined as the time to reach maximum (peak) plasma concentration following drug administration
Time frame: Up to 24 months
PK parameters: Cmin
Defined as concentration at the end of the dosing interval
Time frame: Up to 24 months
PK Parameters: AUC
Defined as the area under the plasma concentration-time curve
Time frame: Up to 24 months
PK Parameters: CL
Defined as the apparent total body clearance of the drug from plasma
Time frame: Up to 24 months
PK Parameters: Vz
Defined as apparent volume of distribution during terminal phase
Time frame: Up to 24 months
PK Parameters: t1/2
Defined as Elimination half-life (to be used in one-or noncompartmental model)
Time frame: Up to 24 months
Receptor Occupancy
Defined as PD-1 receptor occupancy in peripheral blood samples.
Time frame: Up to 24 months