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

Phase 2TerminatedNCT02010203

Heat Biologics104 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

104

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (19)

University of California at Los Angeles

Los Angeles, California, United States

Skyline Urology

Sherman Oaks, 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

Johns Hopkins University

Baltimore, Maryland, United States

University of Massachusetts

Worcester, Massachusetts, United States

...and 9 more locations

Outcomes

Primary Outcomes

Phase 1: Safety and Tolerability

To evaluate the safety and tolerability of vesigenurtacel-L

Time frame: Up to 3 years.

Phase 2: 1-year Disease-Free Survival

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

Time frame: One year

Secondary Outcomes

Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months

Evaluate the proportion of patients with recurrence at 3, 6, 12, 18, and 24 months

Time frame: Up to 2 years

Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months

Evaluate the proportion of patients with progressive disease at 3, 6, 12, 18, and 24

Time frame: Up to 2 years

Disease-free Survival at 3, 6, 18, and 24 Months

Evaluate Disease Free Survival at 3, 6, 18 and 24 months

Time frame: Up to 2 years

Overall Disease-free Survival

Evaluate overall Disease Free Survival

Time frame: Up to 3 years

Overall Survival, Expressed as the Number of Participants Alive

Evaluate overall survival (OS)

Time frame: Up to 3 years

Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months

Time frame: Up to 2 years

Proportion of Patients Undergoing Cystectomy by 12 and 24 Months

Evaluate the proportion of patients undergoing cystectomy by 12 and 24 months from randomization

Time frame: Up to 2 years

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.

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

Time frame: Up to 2 years

Immunologic Response of Peripheral Blood Mononuclear Cells (PBMCs) and Stimulation Analysis Via ICS in Baseline and Post-treatment Biopsies, if Clinically Indicated

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)

Time frame: Up to 3 years

Total PBMC Counts by Flow Cytometry

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)

Time frame: Up to 3 years

Tumor Antigen Expression

Evaluation of pre-treatment tumor tissue for antigen expression

Time frame: At screening

Tumor Infiltrating Lymphocytes (TILs)

Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs

Time frame: Up to 3 years

T Cell Receptor Sequencing of Peripheral Blood T Cells Before and During Treatment

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.

Time frame: Up to 2 years

Safety of the Combination of the HS-410 and BCG

Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG

Time frame: Up to 1 year

Safety of the High Dose HS-410 Monotherapy

Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy

Time frame: Up to 3 years.

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

Overview

Conditions

Interventions

Eligibility

Locations (19)

Outcomes

Primary Outcomes

Secondary Outcomes