Study of 2141-V11 in People With Non-muscle Invasive Bladder Cancer That Did Not Respond to Standard Treatment

NCT05126472 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 21-314
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Non-muscle Invasive Bladder Cancer

Keywords

2141-V11; 21-314

Outcome Measures

Primary Outcomes (2)

• 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.

  2 years

• 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.

  1 year

Study Arms (3)

(Cohort A) anti-CD40 antibody 2141-V11

EXPERIMENTAL

Intravesically or intratumorally) of an anti-CD40 agonist antibody (2141-V11) for the treatment of subjects with BCG-unresponsive NMIBC who are considered ineligible for or have elected not to undergo radical cystectomy.

Drug: anti-CD40 antibody 2141-V11

(Cohort B) 2141-V11, a fixed dose of 10mg

EXPERIMENTAL

For patients who are ineligible for radical cystectomy or have elected not to undergo the procedure.

Drug: anti-CD40 antibody 2141-V11

(Cohort C) expansion cohort 10 mg of 2141-V11

EXPERIMENTAL

For patients in Cohort C, 10 mg of 2141-V11 will be administered as an intratumoral injection during standard of care cystoscopy prior to and within four weeks of planned radical cystectomy.

Drug: anti-CD40 antibody 2141-V11

Interventions

anti-CD40 antibody 2141-V11 DRUG

Cohort 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.

(Cohort A) anti-CD40 antibody 2141-V11

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohorts A and B
• 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
• In this context, adequate BCG therapy is defined as at least one of the following:
• At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy
• At least five of six doses of an initial induction course plus at least two of six doses of a second induction course
• Disease unresponsive to adequate BCG therapy is defined as the following. Suspected recurrence from suspicious cytology or cystoscopy, and later confirmed via TURBT, is acceptable:
• Persistent or recurrent CIS alone or with recurrent Ta/T1 disease (noninvasive papillary disease/tumor invades the subepithelial connective tissue) within 12 months of completion of adequate BCG therapy
• Recurrent HG Ta/T1 disease within 6 months of completion of adequate BCG therapy
• HG T1 disease at the first evaluation following an induction BCG course
• Cohort C:
• Bladder cancer of any stage that has a predominant urothelial histology.
• Stage, grade, and histology must be confirmed by the MSK Department of Pathology

You may not qualify if:

• (Cohort A and B)
• 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
• Exceptions include:
• Cohorts A and B Exceptions: Subjects on topical therapy (e.g. topical 5-
• Cohort C Exceptions: Subjects on topical therapy (e.g. topical 5-fluorouracil) and Neoadjuvant chemotherapy (e.g. cisplatin and gemcitabine)
• Has undergone any intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting trial treatment (a single dose of intravesical treatment given as part of the most recent cystoscopy/TURBT, during the screening period, such as with chemotherapy as per local/regional practices, is acceptable).
• Has had prior chemotherapy, targeted small molecule therapy, cytokine therapy, or radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to a previously administered agent.
• °Subjects with Grade ≤2 neuropathy or Grade ≤2 alopecia are an exception to this criterion and may qualify for the study
• Major surgery or a wound that has not fully healed within 4 weeks prior to the first dose of trial treatment.
• ° If subject has undergone major surgery greater than 4 weeks prior, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting trial therapy
• Known additional malignancy that has had progression or has required active treatment in the last three years
• Exceptions include:
• Basal cell carcinoma of the skin

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Pin Down Bladder Cancer Research Foundation: collaborator
• Rockefeller University: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Bernard Bochner, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bernard Bochner, MD

CONTACT

646-422-4387; bochnerb@mskcc.org

Eugene Pietzak, MD

CONTACT

646-422-4781

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I, open-label study to assess safety and tolerability of a local delivery (intravesically or intratumorally) of an anti-CD40 agonist antibody (2141-V11) for the treatment of subjects with BCG-unresponsive NMIBC who are considered ineligible for or have elected not to undergo radical cystectomy.

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: November 19, 2021
• Study Start: November 8, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (7)