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

• Sponsor: Heat Biologics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02010203
• Collaborator: (none)
• Enrollment: 104
• Locations: 19
• Arms: 5
• Duration (Months): 52
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 (110^6 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 (110^{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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Biological: HS-410; Biological: Placebo; Biological: BCG	Phase 1/Phase 2

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 (110^6 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 (110^{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 Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

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: Placebo; Injection containing sterile solution but no cells; Biological: BCG; Vaccine derived from a live bacterium; Other Names: Bacillus Calmette-Guerin
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

Outcome Measures

Primary Outcome Measures

1. Phase 1: Safety and Tolerability [Up to 3 years.]

   To evaluate the safety and tolerability of vesigenurtacel-L

2. 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

1. 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

2. 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

3. 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

4. Overall Disease-free Survival [Up to 3 years]

   Evaluate overall Disease Free Survival

5. Overall Survival, Expressed as the Number of Participants Alive [Up to 3 years]

   Evaluate overall survival (OS)

6. Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months [Up to 2 years]

7. 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

8. 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

9. 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)

10. 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)

11. Tumor Antigen Expression [At screening]

    Evaluation of pre-treatment tumor tissue for antigen expression

12. Tumor Infiltrating Lymphocytes (TILs) [Up to 3 years]

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

13. 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.

14. 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

15. Safety of the High Dose HS-410 Monotherapy [Up to 3 years.]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at Los Angeles	Los Angeles	California	United States	90095
2	Skyline Urology	Sherman Oaks	California	United States	91411
3	Skyline Urology	Torrance	California	United States	90505
4	Urology Center of Colorado	Denver	Colorado	United States	80211
5	University of Chicago	Chicago	Illinois	United States	60637
6	First Urology	Jeffersonville	Indiana	United States	47130
7	Horizon Oncology Research	Lafayette	Indiana	United States	47905
8	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
9	Johns Hopkins University	Baltimore	Maryland	United States	21287
10	University of Massachusetts	Worcester	Massachusetts	United States	01655
11	University of Minnesota	Minneapolis	Minnesota	United States	55455
12	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
13	Montefiore Medical Center	Bronx	New York	United States	10471
14	University of North Carolina Chapel Hill	Chapel Hill	North Carolina	United States	27599
15	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
16	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
17	Urology of North Texas	Dallas	Texas	United States	75231
18	MD Anderson Cancer Center	Houston	Texas	United States	77030
19	Urology of Virginia	Virginia Beach	Virginia	United States	23462

Sponsors and Collaborators

• Heat Biologics

Investigators

• Principal Investigator: Gary Steinberg, MD, University of Chicago

Study Documents (Full-Text)

• Study Protocol - Feb 3, 2016
• Statistical Analysis Plan - Oct 19, 2016

More Information

Publications

None provided.

• Responsible Party: Heat Biologics
• ClinicalTrials.gov Identifier: NCT02010203
• Other Study ID Numbers: HS410-101
• First Posted: Dec 12, 2013
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Heat Biologics: TURBT; Bladder; Cancer; GP96; Vaccine; Immunotherapy; Heat Biologics; BCG; Bacillus Calmette-Guerin; Bacillus Calmette-Guérin
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; BCG Vaccine

Study Results

Participant Flow

Arm/Group Title	Phase I: HS-410 Low Dose	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Period Title: Overall Study
STARTED	10	26	26	26	16
COMPLETED	10	17	16	23	3
NOT COMPLETED	0	9	10	3	13

Baseline Characteristics

Arm/Group Title	Phase I: HS-410 Low Dose	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410	Total
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96	Total of all reporting groups
Overall Participants	10	26	26	26	16	104
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 10%	7 26.9%	12 46.2%	6 23.1%	1 6.3%	27 26%
>=65 years	9 90%	19 73.1%	14 53.8%	20 76.9%	15 93.8%	77 74%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.2 (7.495)	70.5 (11.176)	68.58 (11.518)	70.58 (9.047)	72.50 (9.784)	70.60 (10.172)
Sex: Female, Male (Count of Participants)
Female	1 10%	3 11.5%	5 19.2%	6 23.1%	3 18.8%	18 17.3%
Male	9 90%	23 88.5%	21 80.8%	20 76.9%	13 81.3%	86 82.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 3.8%	2 7.7%	2 7.7%	0 0%	5 4.8%
Not Hispanic or Latino	10 100%	25 96.2%	24 92.3%	24 92.3%	16 100%	99 95.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 3.8%	0 0%	0 0%	1 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	2 7.7%	0 0%	2 1.9%
White	10 100%	26 100%	25 96.2%	23 88.5%	16 100%	100 96.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	1 3.8%	0 0%	1 1%
Region of Enrollment (participants) [Number]
United States	10 100%	26 100%	26 100%	26 100%	16 100%	104 100%

Outcome Measures

1. Primary Outcome

Title	Phase 1: Safety and Tolerability
Description	To evaluate the safety and tolerability of vesigenurtacel-L
Time Frame	Up to 3 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I: HS-410 Low Dose
Arm/Group Description	HS-410 is given as 1*10^6 cells per dose for 12 weekly injections followed by 3 monthly injections.
Measure Participants	10
Gastrointestinal Disorders	3 30%
General Disorders & Administration Site Conditions	5 50%
Musculoskeletal & Connective Tissue Disorders	1 10%

2. Primary Outcome

Title	Phase 2: 1-year Disease-Free Survival
Description	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

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	26	26	26	16
Count of Participants [Participants]	7 70%	9 34.6%	6 23.1%	12 46.2%

3. Secondary Outcome

Title	Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months
Description	Evaluate the proportion of patients with recurrence at 3, 6, 12, 18, and 24 months
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	26	26	26	16
3 months	22 220%	19 73.1%	23 88.5%	14 53.8%
6 months	19 190%	19 73.1%	22 84.6%	9 34.6%
12 months	18 180%	17 65.4%	21 80.8%	4 15.4%
18 months	18 180%	16 61.5%	15 57.7%	2 7.7%
24 months	14 140%	14 53.8%	12 46.2%	1 3.8%

4. Secondary Outcome

Title	Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months
Description	Evaluate the proportion of patients with progressive disease at 3, 6, 12, 18, and 24
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	26	26	26	16
3 Months	1 10%	1 3.8%	0 0%	0 0%
6 Months	2 20%	3 11.5%	0 0%	3 11.5%
12 Months	2 20%	3 11.5%	1 3.8%	3 11.5%
18 Months	2 20%	3 11.5%	2 7.7%	4 15.4%
24 Months	2 20%	3 11.5%	2 7.7%	4 15.4%

5. Secondary Outcome

Title	Disease-free Survival at 3, 6, 18, and 24 Months
Description	Evaluate Disease Free Survival at 3, 6, 18 and 24 months
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	26	26	26	16
3 months	22 220%	19 73.1%	23 88.5%	14 53.8%
6 months	19 190%	19 73.1%	22 84.6%	9 34.6%
12 months	18 180%	17 65.4%	21 80.8%	4 15.4%
18 months	17 170%	16 61.5%	15 57.7%	2 7.7%
24 months	13 130%	14 53.8%	12 46.2%	1 3.8%

6. Secondary Outcome

Title	Overall Disease-free Survival
Description	Evaluate overall Disease Free Survival
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	26	26	26	16
Number [participants]	18 180%	17 65.4%	18 69.2%	3 11.5%

7. Secondary Outcome

Title	Overall Survival, Expressed as the Number of Participants Alive
Description	Evaluate overall survival (OS)
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	26	26	26	16
Number [participants]	26 260%	26 100%	26 100%	16 61.5%

8. Secondary Outcome

Title	Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium
Measure Participants	26	26	26
12 Month	8 80%	6 23.1%	10 38.5%
24 Months	8 80%	7 26.9%	11 42.3%

9. Secondary Outcome

Title	Proportion of Patients Undergoing Cystectomy by 12 and 24 Months
Description	Evaluate the proportion of patients undergoing cystectomy by 12 and 24 months from randomization
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Phase I is not applicable since the Outcome Measure is solely for Phase II; as pre-specified, only Phase II data would be collected.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	26	26	26	16
12 Months	0 0%	0 0%	0 0%	1 3.8%
24 Months	1 10%	0 0%	0 0%	1 3.8%

10. Secondary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 10 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 11 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

12. Secondary Outcome

Title	Total PBMC Counts by Flow Cytometry
Description	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

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 12 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

13. Secondary Outcome

Title	Tumor Antigen Expression
Description	Evaluation of pre-treatment tumor tissue for antigen expression
Time Frame	At screening

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 13 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

14. Secondary Outcome

Title	Tumor Infiltrating Lymphocytes (TILs)
Description	Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 14 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 15 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

16. Secondary Outcome

Title	Safety of the Combination of the HS-410 and BCG
Description	Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 16 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

17. Secondary Outcome

Title	Safety of the High Dose HS-410 Monotherapy
Description	Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy
Time Frame	Up to 3 years.

Outcome Measure Data

Analysis Population Description

Data were not collected as pre-specified in Outcome Measure 17 due to study termination by the Sponsor.

Arm/Group Title	Phase II: HS-410 Low-Dose Plus BCG	Phase II: High-Dose HS-410 Plus BCG	Phase II: Placebo Plus BCG	Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium	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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
Measure Participants	0	0	0	0

Adverse Events

Time Frame	AEs were defined as all reported events with a start date on or after Study Day 1. All AEs were collected through 30 days post last dose, up to 3 years.
Arm/Group Title	Phase I: HS-410 Low Dose		Phase II: HS-410 Low-Dose Plus BCG		Phase II: High-Dose HS-410 Plus BCG		Phase II: Placebo Plus BCG		Phase II: High-Dose HS-410
Arm/Group Description	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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96		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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium		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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 BCG: Vaccine derived from a live bacterium		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. Placebo: Injection containing sterile solution but no cells BCG: Vaccine derived from a live bacterium		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. HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
All Cause Mortality
	Phase I: HS-410 Low Dose		Phase II: HS-410 Low-Dose Plus BCG		Phase II: High-Dose HS-410 Plus BCG		Phase II: Placebo Plus BCG		Phase II: High-Dose HS-410
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/26 (0%)		0/26 (0%)		0/26 (0%)		0/16 (0%)
Serious Adverse Events
	Phase I: HS-410 Low Dose		Phase II: HS-410 Low-Dose Plus BCG		Phase II: High-Dose HS-410 Plus BCG		Phase II: Placebo Plus BCG		Phase II: High-Dose HS-410
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		8/26 (30.8%)		4/26 (15.4%)		1/26 (3.8%)		2/16 (12.5%)
Blood and lymphatic system disorders
Anaemia	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Cardiac disorders
Cardiac Failure Congestive	0/10 (0%)	0	0/26 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/16 (0%)	0
Atrial Fibrillation	0/10 (0%)	0	0/26 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/16 (0%)	0
Gastrointestinal disorders
Rectal Haemorrhage	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
General disorders
Pyrexia	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Disease Progression	0/10 (0%)	0	0/26 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/16 (0%)	0
Infections and infestations
Urinary Tract Infection	0/10 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Sepsis	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Musculoskeletal and connective tissue disorders
Prostate Cancer	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	1/26 (3.8%)	1	0/16 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Nervous system disorders
Transient Ischaemic Attack	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Cerebrovascular Accident	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Psychiatric disorders
Mental Status Changes	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Renal and urinary disorders
Cystoprostatectomy	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Urinary Retention	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Bladder Perforation	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Reproductive system and breast disorders
Priapism	0/10 (0%)	0	0/26 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Vascular disorders
Aneurysm	0/10 (0%)	0	1/26 (3.8%)	2	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Haematoma	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Phase I: HS-410 Low Dose		Phase II: HS-410 Low-Dose Plus BCG		Phase II: High-Dose HS-410 Plus BCG		Phase II: Placebo Plus BCG		Phase II: High-Dose HS-410
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/10 (70%)		24/26 (92.3%)		19/26 (73.1%)		20/26 (76.9%)		9/16 (56.3%)
Blood and lymphatic system disorders
Anemia	0/10 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Ear and labyrinth disorders
Vertigo	0/10 (0%)	0	0/26 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	0/16 (0%)	0
Endocrine disorders
Hyperadrenalism	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Eye disorders
Dry Eye	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Vision Blurred	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Eye Haemorrhage	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Gastrointestinal disorders
Constipation	0/10 (0%)	0	1/26 (3.8%)	1	1/26 (3.8%)	1	2/26 (7.7%)	2	0/16 (0%)	0
Diarrhoea	3/10 (30%)	3	0/26 (0%)	0	4/26 (15.4%)	6	0/26 (0%)	0	0/16 (0%)	0
Dry Mouth	0/10 (0%)	0	1/26 (3.8%)	1	2/26 (7.7%)	2	1/26 (3.8%)	1	0/16 (0%)	0
Nausea	0/10 (0%)	0	1/26 (3.8%)	1	6/26 (23.1%)	7	1/26 (3.8%)	1	0/16 (0%)	0
Vomiting	0/10 (0%)	0	2/26 (7.7%)	2	5/26 (19.2%)	8	0/26 (0%)	0	0/16 (0%)	0
Dental Caries	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
General disorders
Asthenia	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	2/26 (7.7%)	2	0/16 (0%)	0
Chills	0/10 (0%)	0	5/26 (19.2%)	10	4/26 (15.4%)	5	3/26 (11.5%)	3	0/16 (0%)	0
Fatigue	0/10 (0%)	0	10/26 (38.5%)	14	6/26 (23.1%)	11	4/26 (15.4%)	4	3/16 (18.8%)	3
Influenza Like Illness	0/10 (0%)	0	1/26 (3.8%)	1	2/26 (7.7%)	2	0/26 (0%)	0	0/16 (0%)	0
Malaise	0/10 (0%)	0	1/26 (3.8%)	1	1/26 (3.8%)	1	0/26 (0%)	0	1/16 (6.3%)	1
Pain	0/10 (0%)	0	1/26 (3.8%)	1	2/26 (7.7%)	3	3/26 (11.5%)	3	0/16 (0%)	0
Pyrexia	0/10 (0%)	0	5/26 (19.2%)	7	3/26 (11.5%)	3	3/26 (11.5%)	4	0/16 (0%)	0
Injection Site Pain	4/10 (40%)	4	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Injection Site Erythema	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Infections and infestations
Cystitis	0/10 (0%)	0	0/26 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	0/16 (0%)	0
Folliculitis	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Herpes Zoster	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Nasopharyngitis	0/10 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	1/26 (3.8%)	1	1/16 (6.3%)	1
Pharyngitis Streptococcal	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Upper Respiratory Tract Infection	0/10 (0%)	0	0/26 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	0/16 (0%)	0
Urinary Tract Infection	1/10 (10%)	1	8/26 (30.8%)	8	3/26 (11.5%)	4	6/26 (23.1%)	7	0/16 (0%)	0
Investigations
Blood Urine Present	0/10 (0%)	0	2/26 (7.7%)	2	2/26 (7.7%)	2	2/26 (7.7%)	2	0/16 (0%)	0
Hematocrit Decreased	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
White Blood Cell Count Increased	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Metabolism and nutrition disorders
Decreased Appetite	0/10 (0%)	0	1/26 (3.8%)	1	2/26 (7.7%)	2	2/26 (7.7%)	2	0/16 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/10 (10%)	1	1/26 (3.8%)	1	2/26 (7.7%)	3	1/26 (3.8%)	1	3/16 (18.8%)	4
Back Pain	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	3/26 (11.5%)	3	1/16 (6.3%)	1
Musculoskeletal Pain	0/10 (0%)	0	0/26 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	1/16 (6.3%)	1
Myalgia	0/10 (0%)	0	1/26 (3.8%)	1	1/26 (3.8%)	1	0/26 (0%)	0	1/16 (6.3%)	1
Pain in Extremity	0/10 (0%)	0	1/26 (3.8%)	1	2/26 (7.7%)	2	2/26 (7.7%)	4	0/16 (0%)	0
Flank Pain	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Nervous system disorders
Cerebrovascular Disorder	0/10 (0%)	0	2/26 (7.7%)	2	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Dizziness	0/10 (0%)	0	2/26 (7.7%)	2	1/26 (3.8%)	1	1/26 (3.8%)	1	1/16 (6.3%)	2
Headache	0/10 (0%)	0	2/26 (7.7%)	4	2/26 (7.7%)	2	0/26 (0%)	0	1/16 (6.3%)	1
Psychiatric disorders
Insomnia	0/10 (0%)	0	0/26 (0%)	0	1/26 (3.8%)	1	3/26 (11.5%)	4	0/16 (0%)	0
Renal and urinary disorders
Bladder Perforation	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Bladder Spasm	0/10 (0%)	0	0/26 (0%)	0	4/26 (15.4%)	4	2/26 (7.7%)	3	0/16 (0%)	0
Dysuria	0/10 (0%)	0	3/26 (11.5%)	10	6/26 (23.1%)	18	9/26 (34.6%)	11	0/16 (0%)	0
Haematuria	0/10 (0%)	0	6/26 (23.1%)	9	5/26 (19.2%)	13	3/26 (11.5%)	4	0/16 (0%)	0
Lower Urinary Tract Symptoms	0/10 (0%)	0	1/26 (3.8%)	1	2/26 (7.7%)	2	0/26 (0%)	0	0/16 (0%)	0
Micturition Urgency	0/10 (0%)	0	5/26 (19.2%)	5	4/26 (15.4%)	19	3/26 (11.5%)	6	0/16 (0%)	0
Pollakiuria	0/10 (0%)	0	5/26 (19.2%)	6	4/26 (15.4%)	18	3/26 (11.5%)	5	1/16 (6.3%)	1
Urinary Incontinence	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	2/26 (7.7%)	2	0/16 (0%)	0
Urinary Retention	0/10 (0%)	0	1/26 (3.8%)	1	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Bladder Spasm	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Nephrolithiasis	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Nephropathy	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Pollakiuria	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Urinary Retention	1/10 (10%)	1	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/16 (0%)	0
Reproductive system and breast disorders
Breast Tenderness	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/10 (0%)	0	2/26 (7.7%)	2	3/26 (11.5%)	4	2/26 (7.7%)	2	1/16 (6.3%)	1
Oropharyngeal Pain	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	2/26 (7.7%)	2	0/16 (0%)	0
Upper Airway Cough Syndrome	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Eczema	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	2/26 (7.7%)	2	0/16 (0%)	0
Pruritis	1/10 (10%)	1	2/26 (7.7%)	2	1/26 (3.8%)	1	3/26 (11.5%)	5	0/16 (0%)	0
Urticaria	0/10 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	0/26 (0%)	0	1/16 (6.3%)	1
Vascular disorders
Hypertension	0/10 (0%)	0	2/26 (7.7%)	2	1/26 (3.8%)	1	1/26 (3.8%)	1	0/16 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.