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

NCT02010203 | Terminated Phase 1 Results DMC

• 1 other identifier: HS410-101
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 19

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.

Conditions

Bladder Cancer

Keywords

TURBT; Bladder; Cancer; GP96; Vaccine; Immunotherapy; Heat Biologics; BCG; Bacillus Calmette-Guerin; Bacillus Calmette-Guérin

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (15)

• 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

  Up to 2 years

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

  Up to 2 years

• Overall Disease-free Survival

  Up to 3 years

• Overall Survival, Expressed as the Number of Participants Alive

  Up to 3 years

Study Arms (5)

Phase I: HS-410 Low Dose

EXPERIMENTAL

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

Phase II: HS-410 Low-Dose Plus BCG

EXPERIMENTAL

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; Biological: BCG

Phase II: High-Dose HS-410 Plus BCG

EXPERIMENTAL

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; Biological: BCG

Phase II: Placebo Plus BCG

PLACEBO COMPARATOR

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: Placebo; Biological: BCG

Phase II: High-Dose HS-410

EXPERIMENTAL

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

Interventions

HS-410 BIOLOGICAL

Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96

Phase I: HS-410 Low Dose; Phase II: HS-410 Low-Dose Plus BCG; Phase II: High-Dose HS-410; Phase II: High-Dose HS-410 Plus BCG

Placebo BIOLOGICAL

Injection containing sterile solution but no cells

Phase II: Placebo Plus BCG

BCG BIOLOGICAL

Vaccine derived from a live bacterium

Also known as: Bacillus Calmette-Guerin

Phase II: HS-410 Low-Dose Plus BCG; Phase II: High-Dose HS-410 Plus BCG; Phase II: Placebo Plus BCG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heat Biologics: lead

Study Sites (19)

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Skyline Urology

Sherman Oaks, California, 91411, United States

Location

Skyline Urology

Torrance, California, 90505, United States

Location

Urology Center of Colorado

Denver, Colorado, 80211, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

First Urology

Jeffersonville, Indiana, 47130, United States

Location

Horizon Oncology Research

Lafayette, Indiana, 47905, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Montefiore Medical Center

The Bronx, New York, 10471, United States

Location

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Urology of North Texas

Dallas, Texas, 75231, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Urology of Virginia

Virginia Beach, Virginia, 23462, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplasms

Interventions

BCG Vaccine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Lori McDermott
• Organization: Clinical Development

lmcdermott@heatbio.com

9197948950

Study Officials

• Gary Steinberg, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 12, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: April 1, 2018
• Last Updated: February 17, 2020
• Results First Posted: February 17, 2020

Record last verified: 2020-02

Locations

US (19)