# Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER)

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $656,816

## Abstract

Project Summary: Over 81,000 new individuals are diagnosed each year with urothelial carcinoma
(UC) of the bladder and 17,000 will die from their disease. Most have non-muscle invasive disease
(NMIBC) at diagnosis. Despite standard treatment with the live, attenuated mycobacterial strain Bacillus
Calmette-Guerin (BCG) instilled into the bladder, two-thirds of NMIBC patients will develop relapsed
tumors after BCG treatment. While curative, cystectomy is associated with life-altering quality of life
impact and is not feasible, or is refused, in many. Nonsurgical curative options for BCG-relapsing NMIBC
patients are lacking. In metastatic UC, durable responses with low toxicity rates have been observed with
checkpoint inhibitor (CPI) therapies aimed at the programmed cell death protein 1 (PD-1) / programmed
death-ligand 1 (PD-L1) pathway leading to the FDA approval of five agents. Examining novel combination
approaches including CPIs in BCG-relapsing NMIBC represents a natural next step. In this proposal, we
plan to define the safety and clinical activity, assess the point-of-care diagnostic potential of several genomic
biomarker platforms, and perform initial mechanistic investigations of novel combinations of CPI therapy
with both BCG and radiation in the multi-arm, multi-stage ADAPT-BLADDER phase 1b/2 clinical trial,
with the long-term goal of informing the design of future practice-changing phase 3 trials.
Objectives: 1) To demonstrate safety and clinical efficacy of immunotherapy combination regimens in
patients with BCG-relapsing NMIBC; 2) To identify conserved candidate genomic signatures associated with
clinical benefit and/or treatment resistance to novel immunotherapy regimens in NMIBC patients with recurrent
tumors after prior BCG therapy; 3) To demonstrate the existence of tumor antigen-specific T-cell responses and
correlate such responses with clinical outcomes to novel immunotherapy regimens in NMIBC patients with
recurrent tumors after prior BCG therapy.
Methods: We will assess each objective prospectively through the multi-center phase 1 b / 2 ADAPT-
BLADDER trial in over 170 patients with BCG-relapsing NMIBC. Specifically, we will document the safety
of each regimen in phase 1 and clinical efficacy in phase 2. We will correlate baseline and post-
treatment genomic biomarker signatures with clinical benefit. Lastly, we will interrogate the ability of
personalized neoantigen peptide libraries to expand antigen-specific T-cell clones.
We hypothesize that immunotherapy combination regimens will be safe and effective. Moreover, we
anticipate the identification of point-of-care genomic biomarker signatures that can distinguish patients
most likely to benefit; we expect to identify novel gene expression signatures predictive of therapy
response and resistance; and we suspect the planned functional tumor immunology investigations will
yield illuminating discoveries.

## Key facts

- **NIH application ID:** 9868289
- **Project number:** 5R01CA235681-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Noah M Hahn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $656,816
- **Award type:** 5
- **Project period:** 2019-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868289

## Citation

> US National Institutes of Health, RePORTER application 9868289, Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER) (5R01CA235681-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9868289. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*