The purpose of this multicenter, open label trial (NAPISTAR 1-01) is to evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040 and to find the best dose of TUB-040 in participants with ovarian cancer and Non Small Cell Lung Cancer. TUB-040 is an antibody-drug-conjugate which delivers a topoisomerase I inhibitor to tumor cells which overexpress the target NaPi2b. The study consists of three parts: In dose escalation, ovarian cancer participants and lung cancer participants receive increasing doses of TUB-040 until the maximal tolerated dose is found. In dose optimization, at least two doses are compared with each other to determine which dose is optimal for participants. In dose expansion, a single dose will be used in a larger number of participants. TUB-040 is given IV every 3 weeks until the disease progresses or the participants has to stop due to side effects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
250
A complete treatment cycle is defined as 21 calendar days. TUB-040 will be administered as an intravenous (IV) solution on day 1 of each treatment cycle
The University of Alabama
Birmingham, Alabama, United States
RECRUITINGYale Cancer Center
New Haven, Connecticut, United States
NOT_YET_RECRUITINGEmory University
Atlanta, Georgia, United States
NOT_YET_RECRUITINGNorton Cancer Institute Research
Louisville, Kentucky, United States
Phase 1: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)[
Time frame: First dose up to 21 days
Phase 1 and 2a: Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs)
Time frame: First dose date up to 30 days post last dose (Up to 3 years)
Phase 2a & 2b: Overall Response Rate (ORR) by Blinded Independent Central Review (BICR)
ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by BICR.
Time frame: Up to 3 years
Phase 2a & 2b: Duration of Response (DOR) by BICR
DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by BICR.
Time frame: Up to 3 years
Phase 1, 2a & 2b: ORR by INV
ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by Investigator (INV).
Time frame: Up to 3 years
Phase 1, 2a & 2b: DOR by INV
DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by INV.
Time frame: Up to 3 years
Phase 1, 2a & 2b: Progression-Free Survival (PFS) by INV
PRS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by INV.
Time frame: Up to 3 years
Phase 1, 2a & 2b: Disease Control Rate (DCR) by INV
DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by INV.
Time frame: Up to 3 years
Phase 2a & 2b: Progression-Free Survival (PFS) by BICR
PRS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by BICR.
Time frame: Up to 3 years
Phase 2a & 2b: Disease Control Rate (DCR) by BICR
DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by BICR.
Time frame: Up to 3 years
Phase 1, 2a & 2b: Percentage of Participants Experiencing Grade ≥3 Lab Abnormalities
Time frame: First dose date up to last dose date plus 30 days
Phase 1: Percentage of Participants Experiencing Serious Adverse Events (SAEs)
Time frame: First dose date up to 30 days post last dose (Up to 3 years)
Phase 1 & 2a: Pharmacokinetic (PK) Parameter of TUB-040, total mAb, and Free Exatecan: Cmax
Cmax is defined as the maximum observed drug concentration.
Time frame: Up to 3 years
Phase 1 & 2a: PK Parameter of TUB-040, Total mAb, and Free Exatecan: Cmin
The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Cmin will be derived).
Time frame: Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Tmax
Tmax is defined as the time (observed time point) of Cmax.
Time frame: Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Area Under Curve (AUC)
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time frame: Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Half life (T1/2)
T1/2 is defined as the terminal elimination half-life at steady state.
Time frame: Up to 3 years
Phase 1, 2a & 2b: Percentage of Participants Developing anti-TUB-040 antibodies and semiquantitative titer assessments
Time frame: From enrollment until 30 days after last study drug
Phase 2a & 2b: Overall Survival (OS)
OS is defined as the length of time from first dose until the date of death from any cause.
Time frame: Up to 3 years
Phase 2a & 2b: CA-125 response according to Gynecological Cancer InterGroup (GCIG)
Time frame: Up to 3 years
Phase 2a & 2b: Percentage of Participants Experiencing TEAEs
Time frame: First dose date up to 30 days post last dose date (Up to 3 years)
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Tufts
Boston, Massachusetts, United States
NOT_YET_RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
NOT_YET_RECRUITINGSTART New Jersey East Brunswick
East Brunswick, New Jersey, United States
RECRUITINGMount Sinai
New York, New York, United States
RECRUITINGChrist Hospital
Cincinnati, Ohio, United States
RECRUITINGOhio State University
Columbus, Ohio, United States
RECRUITING...and 19 more locations