The purpose of this study is to test the safety of the study drug 2141-V11 in people whose NMIBC did not respond to standard treatment, and who will not have the standard surgical procedure to remove the bladder. The researchers will test different doses of 2141-V11 to see which dose is safest in people. The researchers will also do tests to see how the body absorbs, distributes, and gets rid of 2141-V11. This study is one of the first to test 2141-V11 in people, and the first to test 2141-V11 delivered through a catheter into the bladder.
High-grade (HG) NMIBC (HG Ta, CIS, and/or T1) of urothelial histology that is unresponsive to adequate BCG therapy.
Stage, grade, and histology must be confirmed by the MSK Department of Pathology
Subjects with tumors of mixed urothelial/non-urothelial histology may be included, but urothelial carcinoma must be the predominant histology; subjects with predominant or exclusively non-urothelial histology are excluded
In those subjects with CIS, the CIS must be present on the tumor sample from the most recent cystoscopy/TURBT
History of or currently being treated for muscle-invasive (T2, T3, T4) locally-advanced non-resectable or metastatic urothelial carcinoma.
Evidence of concurrent extravesical (i.e., urethra, ureter, or renal pelvis) urothelial cell carcinoma.
Concurrent anti-cancer therapy, including investigational agents
Cohorts A and B Exceptions: Subjects on topical therapy (e.g. topical 5-
Sequential
anti-CD40 antibody 2141-V11
DrugCohort A Eligible subjects will receive the anti-CD40 antibody 2141-V11 administered by intravesical instillation once weekly for 3 consecutive weeks (weeks 1, 2, and 3) for a total of 3 doses. As discussed further below, depending on disease status at week 13 and week 25 evaluations, subjects may be eligible for re-treatment (once weekly for 3 doses) at these time points.
anti-CD40 antibody 2141-V11
DrugCohort B Part 1 Eligible subjects will receive the anti-CD40 antibody 2141-V11 administered by intratumoral injection once every 3 weeks (weeks 1, 4, 7, and 10) for a total of 4 doses. As discussed further below, depending on disease status at week 14 and week 26 evaluations, subjects may be eligible for re-treatment (once every 3 weeks for a total of 4 doses) at these time points.
anti-CD40 antibody 2141-V11
DrugCohort C Eligible subjects will receive the anti-CD40 antibody 2141-V11 administered by intratumoral injection as a single 10mg during standard of care cystoscopy and examination no sooner than 22 days of the last cycle of neoadjuvant therapy with enfortumab vedotin and pembrolizumab and prior to and within 4 weeks of planned radical cystectomy.
Intravesical Gemcitabine
DrugCohort B Part 2 is a nonblinded, randomized prospective trial to determine whether the combination of gemcitabine with 2141-V11 is more efficacious than gemcitabine monotherapy in patients with BCG-naïve HG Ta NMIBC
Intravesical Gemcitabine with anti-CD40 antibody 2141-V11
DrugCohort B Part 2 is a nonblinded, randomized prospective trial to determine whether the combination of gemcitabine with 2141-V11 is more efficacious than gemcitabine monotherapy in patients with BCG-naïve HG Ta NMIBC
MTD/RP2D (Cohort A)
The MTD will be defined as the dose level at which the estimated DLT rate from the MCRM model is closest to the target acceptable rate of 20%. If an MTD is not found after the full dose escalation study has been completed, the next dose recommended by the MCRM algorithm will be considered the RP2D. A DLT will be defined as the occurrence of any clinically significant grade 3 or 4 AE (per CTCAE version 5.0) within the DLT evaluation period that is considered by the Principal Investigator or designee to be possibly, probably, or definitely related to 2141-V11.
Reported number of adverse events from baseline (start of 2141-V11 administration) up until the last follow-up visit after 2141-V11 administration (Cohort B)
AE severity should be graded using CTCAE version 5.0.
recurrence-free survival (RFS) Cohort B Part 2
Progression of disease
in all subjects will be defined as development of metastatic disease or death following radical cystectomy
Click on the lead sponsor to view all of their trials.
Memorial Sloan Kettering Cancer Center
Lead sponsor
Pin Down Bladder Cancer Research Foundation
Collaborator
Rockefeller University
Collaborator
