NPX372 is an antibody drug (protein drug) that blocks a specific protein which is found to be increased on the surface of cancer cells called B7-H7 and, at the same time, binds to immune cells (T cells) through a receptor called CD3. The effect of this binding is to activate T cells to kill cancer cells with B7-H7. In this research study we are: * Evaluating the safety and possible effectiveness of NPX372. * Identifying a safe and tolerable dose or doses for further study. Participants who are treated will receive an intravenous (IV) infusion of NPX372 if their disease has not progressed, and be closely monitored by the treating physicians.
NPX372 is being developed as a therapeutic in solid tumor malignancies including non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), pancreatic adenocarcinoma (PDAC), biliary tract tumors, ovarian carcinoma, and gastric/gastro-esophageal carcinoma. This study is a Phase 1 study with primary dose-escalation occurring in the aforementioned solid tumor malignancies (main cohorts). Backfill cohorts from a selected subset of these tumor types will be utilized to enrich for dose optimization in participants whose tumors have high B7-H7 expression determined by prospective screening of archival tissue.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
81
NPX372 is administered by IV infusion. The first cycle will be 3 weeks long and NPX372 will be given on the first day and one week later during this 3-week period. For most dose levels, the first day's dose (C1D1) will be a lower dose, which will serve as a "priming dose". The full dose will start on the second dose. After the first two doses, NPX372 will be administered every other week for up to 6 months. After that time, NPX372 will be given about once a month. Treatment may continue for up to 2 years as long as the patient is deriving benefit.
University of California - San Diego
La Jolla, California, United States
RECRUITINGJohns Hopkins
Baltimore, Maryland, United States
RECRUITINGMontefiore
The Bronx, New York, United States
RECRUITINGSarah Cannon Research Institute
Nashville, Tennessee, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGNEXT
Fairfax, Virginia, United States
RECRUITINGIncidence of Dose Limiting Toxicity (DLT)
Number of participants with DLT
Time frame: From first dose through 21 days
Overall incidence of Dose Limiting Equivalent Toxicity (DLET) during treatment
Number of participants with DLET
Time frame: From first dose up to 24 months
Incidence of AEs, characterized overall and by type, seriousness, relationship to NPX372, and severity.
Number and type of AEs categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: From first dose up to 24 months
Number of participants with abnormal laboratory parameters, vital signs, electrocardiogram (ECG) parameters, physical examination findings as characterized by type, frequency, timing, relationship to NPX372, and severity
Time frame: From first dose up to 24 months
Drug discontinuation, drug interruptions/delays and dose reductions due to treatment-related AEs
Number of participants with changes to their dosing schedule as a result of treatment-related AEs
Time frame: From first dose up to 24 months
Number of participants with AEs, DLTs (inclusive of DLETs), and PD changes within blood
Time frame: From first dose up to 24 months
Objective Response Rate (ORR)
ORR: the proportion of participants with best overall response, i.e., complete response (CR) or partial response (PR), per RECIST 1.1
Time frame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first
Duration of Response (DOR)
DOR: the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the Investigator using RECIST 1.1 or death from any cause, whichever comes first.
Time frame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first
Disease Control Rate (DCR)
DCR: the proportion of participants with a best ORR + Stable Disease (SD)
Time frame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first]
Progression-Free Survival (PFS)
PFS: the duration from the start of treatment until tumor progression or death of any cause
Time frame: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first
NPX372 serum PK (Cmax)
Cmax - measurement of highest NPX372 plasma concentration over time
Time frame: Following dose on Day 1 for Cycle 1 (21 days). Following dose on Day 1 for Cycles 2 through 7 (28 days). Following dose on Day 1 every 3 cycles up to the end of treatment and 90-day follow-up after Cycle 7 (28 days)
NPX372 serum PK (AUC0-last)
AUC-last: measurement of total NPX372 plasma concentration over time
Time frame: Following dose on Day 1 for Cycle 1 (21 days). Following dose on Day 1 for Cycles 2 through 7 (28 days). Following dose on Day 1 every 3 cycles up to the end of treatment and 90-day follow-up after Cycle 7 (28 days)
NPX372 serum PK time of Cmax (Tmax)
Tmax - time to NPX372 maxiumum plasma concentration
Time frame: Following dose on Day 1 for Cycle 1 (21 days). Following dose on Day 1 for Cycles 2 through 7 (28 days). Following dose on Day 1 every 3 cycles up to the end of treatment and 90-day follow-up after Cycle 7 (28 days)
NPX372 serum PK terminal half-life (T1/2)
T1/2 - measurement of the clearance of NPX372 from plasma over time
Time frame: Following dose on Day 1 for Cycle 1 (21 days). Following dose on Day 1 for Cycles 2 through 7 (28 days). Following dose on Day 1 every 3 cycles up to the end of treatment and 90-day follow-up after Cycle 7 (28 days)
Degree of accumulation, incidence, and magnitude of ADA
Number of participants with anti-drug antibodies (ADA)
Time frame: Following dose on Day 1 for Cycle 1 (21 days). Following dose on Day 1 for Cycles 2 through 7 (28 days). Following dose on Day 1 every 3 cycles up to the end of treatment and 90-day follow-up after Cycle 7 (28 days)
Overall Survival (OS)
Average length of survival for treated participants
Time frame: From first dose until death from any cause through 24 months
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