Tice BCG (live attenuated bacillus Calmette-Guerin) / Merck (MSD), Texas A&M University - LARVOL DELTA

In-home Intravesical Chemotherapy for the Treatment of Bladder Cancer, INVITE Trial (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

S1602: Different Strains of BCG With or Without Vaccine in High Grade Non- Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: SWOG Cancer Research Network | Trial completion date: Sep 2025 ➔ Jun 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Expanded Access Program for recombinant BCG launches at first US site (Urology Times) - "U.S. Urology Partners has become the first site to offer recombinant BCG (rBCG) through an Expanded Access Program...for patients with non–muscle invasive bladder cancer (NMIBC) who are eligible to receive intravesical TICE BCG, ImmunityBio announced in a news release....The FDA authorized the EAP last month to provide an alternative source of BCG to patients across the US in an effort to address the ongoing BCG shortage."

Trial status • Bladder Cancer • Urothelial Cancer

EVER: Evaluating Safety and Efficacy of Verity-BCG in BCG-naïve Patients with Intermediate and High-risk Non-muscle Invasive Bladder (NMIBC) (clinicaltrials.gov) - P3 | N=540 | Recruiting | Sponsor: Verity Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2026 ➔ Feb 2029 | Trial primary completion date: Dec 2025 ➔ Feb 2029

Enrollment open • Head-to-Head • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

ResQ133A-NMIBC: Intravesical Recombinant Mycobacterium (rMBCG) in Participants With NMIBC Eligible to Receive Intravesical Tice BCG (clinicaltrials.gov) - P1/2 | N=40 | Not yet recruiting | Sponsor: ImmunityBio, Inc.

New P1/2 trial

ALBAN: Atezolizumab Plus One-year BCG Bladder Instillation in BCG-naive High-risk Non-muscle Invasive Bladder Cancer Patients (clinicaltrials.gov) - P3 | N=517 | Active, not recruiting | Sponsor: UNICANCER | Trial primary completion date: Oct 2024 ➔ Jun 2025

Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) (MK-3475-676/KEYNOTE-676) (clinicaltrials.gov) - P3 | N=1397 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 ➔ Nov 2034

Combination therapy • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

In-home Intravesical Chemotherapy for the Treatment of Bladder Cancer, INVITE Trial (clinicaltrials.gov) - P1/2 | N=40 | Not yet recruiting | Sponsor: Mayo Clinic

New P1/2 trial • Gallbladder Cancer • Hepatology • Oncology • Solid Tumor

BCG-therapy for non-muscle-invasive bladder cancer: overview of the current trends (PubMed, Urologiia) - "According to the survey, one third of doctors do not prescribe BCG therapy due to the lack of conditions or a shortage of the drug. An increase of relapse-free survival of patients with NMIBC is possible by providing conditions for intravesical immunotherapy."

Journal • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Tuberculosis • Urology

S1602: Different Strains of BCG With or Without Vaccine in High Grade Non- Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: SWOG Cancer Research Network | Trial completion date: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) (MK-3475-676/KEYNOTE-676) (clinicaltrials.gov) - P3 | N=1397 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ALBAN: Atezolizumab Plus One-year BCG Bladder Instillation in BCG-naive High-risk Non-muscle Invasive Bladder Cancer Patients (clinicaltrials.gov) - P3 | N=516 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Feb 2028 ➔ Oct 2028 | Trial primary completion date: Apr 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

NU 15U06: Pembrolizumab and BCG Solution in Treating Patients With Recurrent Non-Muscle-Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Northwestern University | Active, not recruiting ➔ Completed

IO biomarker • Trial completion • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-1 • PD-L1 • PD-L2

A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG before Intravesical Therapy for BCG-Naïve High-Grade Non-Muscle Invasive Bladder Cancer (SWOG-Spring 2024) - "Participants: SWOG, CTSU (Supported by Alliance, ECOG ACRIN, NRG) Date Closed: 12/15/2020 Objectives To compare whether time to high-grade recurrence (TTHGR) for patients with BCG-naïve, non-muscle invasive bladder cancer (NMIBC) receiving Tokyo- 172 BCG (Arm 2) is non-inferior to patients receiving BCG LIVE (TICE® BCG) (Arm 1)...Twenty-nine patients on the Tokyo- 172 BCG arm experienced Grade 3 adverse events. Three patients on the Prime + Tokyo-172 BCG arm experienced Grade 4 adverse events, two with sepsis and one with dysuria listed as "Renal/urinary disorders-Other." Forty patients on the Prime + Tokyo-172 BCG arm experienced Grade 3 adverse events as maximum degree, primarily noninfective cystitis (7 patients), urinary tract infection (6), hematuria (5), injection site reaction (5), and generalized muscle weakness (3)."

Clinical • P3 data • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Nephrology • Oncology • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor • Squamous Cell Carcinoma • Tuberculosis

Comparing Clinical Efficacy of Different Bacillus Calmette-Guérin Strains in Patients With T1 High Grade Bladder Cancer. (PubMed, Anticancer Res) - "Both the Connaught and TICE strains of BCG demonstrated comparable three-year recurrence-free survival rates and three-year progression-free survival rates for T1 high grade bladder cancer, as well as comparable adverse events. Due to the global BCG shortage, further strain comparisons are essential for clinical validation."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Bacille Calmette-Guerin (BCG) Vaccine for Immune Protection Against Infections (clinicaltrials.gov) - P2 | N=29 | Completed | Sponsor: Johns Hopkins University | Recruiting ➔ Completed | N=180 ➔ 29

Enrollment change • Trial completion • Bronchiectasis • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • IFNG

ALBAN: Atezolizumab Plus One-year BCG Bladder Instillation in BCG-naive High-risk Non-muscle Invasive Bladder Cancer Patients (clinicaltrials.gov) - P3 | N=516 | Active, not recruiting | Sponsor: UNICANCER | Recruiting ➔ Active, not recruiting

Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

BCG+MMC: Adding Mitomycin to BCG as Adjuvant Intravesical Therapy for High-risk Non-Muscle-invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=501 | Active, not recruiting | Sponsor: University of Sydney | Recruiting ➔ Active, not recruiting

Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Genetically engineered Salmonella Typhi as novel microbial immunotherapy for bladder cancer (EACR 2023) - "We established the preclinical safety and efficacy of live-attenuated Salmonella enterica Typhi strain ZH9 as a novel immunotherapy for NMIBC.Material and MethodsZH9 efficacy and mechanism of action (MOA) were tested in the murine orthotopic, syngeneic MB49 tumor model, compared to OncoTICE®BCG...Systemic priming further enhances immune responses and may therefore result in greater efficacy. This suggests that ZH9 immunotherapy may improve outcomes for patients with NMIBC, allowing less aggressive treatment and more reliable manufacturing method than the current SOC."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Bacille Calmette-Guerin (BCG) Vaccine for Immune Protection Against Infections (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Johns Hopkins University | Trial completion date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Bronchiectasis • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • IFNG

High-risk non-muscle invasive bladder cancer (HR-NMIBC) treated with sequential BCG / Electromotive Drug Administration Mitomycin-C (EMDA-MMC): 2% disease-specific mortality at 4 years’ follow-up (AUA 2017) - "BCG (Immucyst until June 2012, Oncotice since Sept 2012) was given in weeks 1 and 2, and EMDA-MMC (40mg, intravesical current 20mA for 30 mins) in week 3, and this cycle was repeated 3 times for a total of 9 weeks. Despite the challenge of a 4-year recurrence rate of 35%, a low progression rate to muscle-invasive and metastatic disease of 5% and disease-specific mortality of 2% continue to attest to the oncological efficacy of sequential BCG/EMDA-MMC."

Clinical • Biosimilar • Bladder Cancer • Oncology • Urothelial Cancer

A phase II trial of intravesical chemoimmunotherapy with gemcitabine and bacillus Calmette-Guérin (BCG) for patients with BCG-exposed, high-grade, non-muscle–invasive bladder cancer. (ASCO-GU 2023) - P1/2 | "Combination BCG with immune checkpoint inhibition is associated with a ~12-18% risk of serious treatment-related adverse events and BCG combined with Mitomycin C (MMC) has unacceptable urinary toxicity...The maximum tolerated dose (MTD) was 2000 mg gemcitabine and 50 mg TICE BCG...Correlative studies explore immune and molecular predictors of response and resistance to chemoimmunotherapy in tumor tissue, urine, and blood. Clinical trial information: NCT04179162."

Clinical • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

S1602: Different Strains of BCG With or Without Vaccine in High Grade Non- Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Southwest Oncology Group | Trial primary completion date: Feb 2023 ➔ Dec 2024

Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: Carman Giacomantonio | N=100 ➔ 0 | Trial completion date: Dec 2031 ➔ Sep 2022 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Dec 2031 ➔ Sep 2022

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial withdrawal • Melanoma • Oncology • Solid Tumor • IL2

Acupuncture for the Treatment of Intravesical BCG-Related Adverse Events in High-Risk Non-muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2 | N=45 | Completed | Sponsor: Fred Hutchinson Cancer Center | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Aug 2022 | Trial primary completion date: Dec 2022 ➔ Aug 2022

Adverse events • Trial completion • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer