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

Phase 1/2, Placebo-Controlled, Randomized Study to Evaluate the Safety, Immune Response & Clinical Activity of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer Who Have Undergone Transurethral Resection of Bladder Tumor (TURBT)

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.

Study Overview

• Status: Terminated
• Conditions: Bladder Cancer
• Intervention / Treatment: Biological: HS-410; Biological: BCG; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles
    • Sherman Oaks, California, United States, 91411
      • Skyline Urology
    • Torrance, California, United States, 90505
      • Skyline Urology
  • Colorado
    • Denver, Colorado, United States, 80211
      • Urology Center of Colorado
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • First Urology
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10471
      • Montefiore Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Chapel Hill
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Urology of North Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: HS-410 Low Dose; 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.	Biological: HS-410; Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Experimental: Phase II: HS-410 Low-Dose Plus 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.	Biological: HS-410; Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96; Biological: BCG; Vaccine derived from a live bacterium; Other Names: Bacillus Calmette-Guerin
Experimental: Phase II: High-Dose HS-410 Plus 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.	Biological: HS-410; Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96; Biological: BCG; Vaccine derived from a live bacterium; Other Names: Bacillus Calmette-Guerin
Placebo Comparator: Phase II: Placebo Plus 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.	Biological: BCG; Vaccine derived from a live bacterium; Other Names: Bacillus Calmette-Guerin; Biological: Placebo; Injection containing sterile solution but no cells
Experimental: Phase II: High-Dose 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.	Biological: HS-410; Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Safety and Tolerability	To evaluate the safety and tolerability of vesigenurtacel-L	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	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	Up to 2 years
Overall Disease-free Survival	Evaluate overall Disease Free Survival	Up to 3 years
Overall Survival, Expressed as the Number of Participants Alive	Evaluate overall survival (OS)	Up to 3 years
Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months		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	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	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)	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)	Up to 3 years
Tumor Antigen Expression	Evaluation of pre-treatment tumor tissue for antigen expression	At screening
Tumor Infiltrating Lymphocytes (TILs)	Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs	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.	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	Up to 1 year
Safety of the High Dose HS-410 Monotherapy	Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy	Up to 3 years.

Collaborators and Investigators

• Sponsor: Heat Biologics
• Investigators: Principal Investigator: Gary Steinberg, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: December 5, 2013
• First Submitted That Met QC Criteria: December 9, 2013
• First Posted (Estimate): December 12, 2013

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; Vaccine; Immunotherapy; Bacillus Calmette-Guérin; Bladder; BCG; Bacillus Calmette-Guerin; TURBT; Heat Biologics; GP96
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; BCG Vaccine
• Other Study ID Numbers: HS410-101