A Phase 1/2 Study of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer After TURBT

Phase 1

Terminated

Conditions: Bladder Cancer

Interventions: Biological: HS-410
Biological: Placebo
Biological: BCG

Registration Number: NCT02010203

Lead Sponsor: Heat Biologics

Brief Summary: Phase I/II study: Phase 1 is an open-label, safety study, patients who previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1\*10\^6 cells) HS-410 monotherapy. Phase 2, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1\*10\^6 cells) or high dose (1\*10\^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. Patients who do not receive BCG will be enrolled into an open-label, non-randomized group receiving high dose (1\*10\^7 cells) intradermal HS-410 monotherapy.

Detailed Description: This study is a two part study: Phase I and Phase II. The Phase 1 portion is an open-label, safety study. Patients will have previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1\*10\^6 cells) HS-410 monotherapy. In Phase 2, patients will be assigned to treatment groups based on whether they will receive induction BCG in the typical post-TURBT window. If the investigator plans to administer BCG, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1\*10\^6 cells) or high dose (1\*10\^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. If patients will not receive BCG, they will be enrolled into an open-label, non-randomized group and receive high dose (1\*10\^7 cells) intradermal HS-410 monotherapy.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 104

Inclusion Criteria

Histologically or cytologically confirmed non-muscle invasive bladder cancer [Ta, T1 or Tis (CIS)] that has been removed by transurethral resection
Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size > 3cm, early recurrence (<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment > 12 months prior to the baseline staging procedure.
Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
Adequate laboratory parameters

Exclusion Criteria

Human immunodeficiency virus (HIV) infection or immunodeficiency disorders, either primary or acquired
Infections or intercurrent illness requiring active therapy
Any condition requiring active steroid or other immunosuppressive therapy
Active malignancies within the past 12 months except negligible risk of metastasis or death treated with expected curative outcome.
Prostate pelvic radiation within the past 12 months
Significant cardiac impairment
Current alcohol or chemical abuse, or mental or psychiatric condition precluding protocol compliance
Pregnant or nursing
Allergy to soy, egg, or peanut products
Receiving another investigational agent (30 day wash-out required prior to first dose)
Neo-adjuvant therapy prior to baseline staging procedures for the current occurrence of non-muscle invasive bladder cancer
Prior treatment with a cancer vaccine for this indication
Prior vaccination with BCG for tuberculosis disease
Prior splenectomy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase II: High-Dose HS-410 Plus BCG	BCG	In the Phase 2 portion, HS-410 is given as 1\*10\^7 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
Phase I: HS-410 Low Dose	HS-410	In the open label Phase 1 portion, HS-410 is given as 1\*10\^6 cells per dose for 12 weekly injections followed by 3 monthly injections.
Phase II: High-Dose HS-410 Plus BCG	HS-410	In the Phase 2 portion, HS-410 is given as 1\*10\^7 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
Phase II: Placebo Plus BCG	BCG	In the Phase 2 portion, a placebo is given weekly for 6 weeks in combination with BCG, followed by 6 weeks of placebo alone, and then 3 courses of three once-weekly doses of placebo in combination with BCG.
Phase II: HS-410 Low-Dose Plus BCG	HS-410	In the Phase 2 portion, HS-410 is given as 1\*10\^6 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
Phase II: HS-410 Low-Dose Plus BCG	BCG	In the Phase 2 portion, HS-410 is given as 1\*10\^6 cells per dose weekly for 6 weeks in combination with BCG, followed by 6 weeks of HS-410 alone, and then 3 courses of three once-weekly doses of HS-410 in combination with BCG.
Phase II: Placebo Plus BCG	Placebo	In the Phase 2 portion, a placebo is given weekly for 6 weeks in combination with BCG, followed by 6 weeks of placebo alone, and then 3 courses of three once-weekly doses of placebo in combination with BCG.
Phase II: High-Dose HS-410	HS-410	In the Phase II portion, if patients will not receive BCG, HS-410 is given as 1\*10\^7 cells per dose weekly for 12 weeks, and then 3 courses of three once-weekly doses of HS-410.

Primary Outcome Measures

Name	Time	Method
Phase 1: Safety and Tolerability	Up to 3 years.	To evaluate the safety and tolerability of vesigenurtacel-L
Phase 2: 1-year Disease-Free Survival	One year	Arm 1, 2, 3: 1-year DFS in patients with NMIBC treated with BCG in combination with blinded study product (one of two doses of vesigenurtacel-L or placebo) Arm 4: 1-year DFS in patients with NMIBC treat1fv 9 with high dose vesigenurtacel-L monotherapy One-year disease-free survival will be defined as the proportion of patients who are free from recurrent disease, progressive disease, and alive one year after the date of randomization/treatment assignment

Secondary Outcome Measures

Name	Time	Method
Safety of the High Dose HS-410 Monotherapy	Up to 3 years.	Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy
Overall Survival, Expressed as the Number of Participants Alive	Up to 3 years	Evaluate overall survival (OS)
Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months	Up to 2 years
T Cell Receptor Sequencing of Peripheral Blood T Cells Before and During Treatment	Up to 2 years	Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs, T cell receptor sequencing of peripheral blood T cells before and during the course of treatment.
Safety of the Combination of the HS-410 and BCG	Up to 1 year	Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG
Immunologic Response of PBMCs Via Intracellular Cytokine Staining (ICS) by Flow Cytometry and/or Enzyme-linked Immunosorbent Spot (ELISPOT) on CD8+ Cells After HS-410 Vaccination as Compared to Baseline.	Up to 2 years	Evaluate the proportion of patients with immunologic response of peripheral blood mononuclear cells (PBMCs) via intracellular cytokine staining (ICS) by flow cytometry and/or ELISPOT on CD8+ cells following vesigenurtacel-L vaccination
Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months	Up to 2 years	Evaluate the proportion of patients with recurrence at 3, 6, 12, 18, and 24 months
Immunologic Response of Peripheral Blood Mononuclear Cells (PBMCs) and Stimulation Analysis Via ICS in Baseline and Post-treatment Biopsies, if Clinically Indicated	Up to 3 years	Evaluate immunologic response of PBMCs (analysis of surface markers, CD3, CD4, CD8, CD19, CD25, CD45, CD56, FoxP3, and degranulation) and stimulation analysis via ICS of interferon gamma (IFNγ) and granzyme B (gzB)
Total PBMC Counts by Flow Cytometry	Up to 3 years	Evaluate total PBMC counts by flow cytometry, including lymphocyte subsets (B cells, helper T-cells, cytotoxic T-cells, natural killer (NK) cells and T-reg)
Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months	Up to 2 years	Evaluate the proportion of patients with progressive disease at 3, 6, 12, 18, and 24
Disease-free Survival at 3, 6, 18, and 24 Months	Up to 2 years	Evaluate Disease Free Survival at 3, 6, 18 and 24 months
Tumor Infiltrating Lymphocytes (TILs)	Up to 3 years	Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs
Overall Disease-free Survival	Up to 3 years	Evaluate overall Disease Free Survival
Proportion of Patients Undergoing Cystectomy by 12 and 24 Months	Up to 2 years	Evaluate the proportion of patients undergoing cystectomy by 12 and 24 months from randomization
Tumor Antigen Expression	At screening	Evaluation of pre-treatment tumor tissue for antigen expression

Trial Locations

Locations (18): Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
University of California at Los Angeles
🇺🇸
Los Angeles, California, United States
Skyline Urology
🇺🇸
Torrance, California, United States
Urology Center of Colorado
🇺🇸
Denver, Colorado, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
First Urology
🇺🇸
Jeffersonville, Indiana, United States
Horizon Oncology Research
🇺🇸
Lafayette, Indiana, United States
University of Kansas Cancer Center
🇺🇸
Westwood, Kansas, United States
University of Massachusetts
🇺🇸
Worcester, Massachusetts, United States
University of North Carolina Chapel Hill
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Chapel Hill, North Carolina, United States
Carolina Urologic Research Center
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Myrtle Beach, South Carolina, United States
Urology of Virginia
🇺🇸
Virginia Beach, Virginia, United States
Urology of North Texas
🇺🇸
Dallas, Texas, United States
MD Anderson Cancer Center
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Houston, Texas, United States
Washington University School of Medicine
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Saint Louis, Missouri, United States
University of Minnesota
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Minneapolis, Minnesota, United States
Montefiore Medical Center
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Bronx, New York, United States
Thomas Jefferson University
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Philadelphia, Pennsylvania, United States