Bladder Cancer
Conditions
Keywords
TURBT, Bladder, Cancer, GP96, Vaccine, Immunotherapy, Heat Biologics, BCG, Bacillus Calmette-Guerin, Bacillus Calmette-Guérin
Brief summary
Phase I/II study: Phase 1 is an open-label, safety study, patients who previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1\*10\^6 cells) HS-410 monotherapy. Phase 2, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1\*10\^6 cells) or high dose (1\*10\^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. Patients who do not receive BCG will be enrolled into an open-label, non-randomized group receiving high dose (1\*10\^7 cells) intradermal HS-410 monotherapy.
Detailed description
This study is a two part study: Phase I and Phase II. The Phase 1 portion is an open-label, safety study. Patients will have previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1\*10\^6 cells) HS-410 monotherapy. In Phase 2, patients will be assigned to treatment groups based on whether they will receive induction BCG in the typical post-TURBT window. If the investigator plans to administer BCG, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1\*10\^6 cells) or high dose (1\*10\^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. If patients will not receive BCG, they will be enrolled into an open-label, non-randomized group and receive high dose (1\*10\^7 cells) intradermal HS-410 monotherapy.
Interventions
BIOLOGICALHS-410
Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
BIOLOGICALPlacebo
Injection containing sterile solution but no cells
BIOLOGICALBCG
Vaccine derived from a live bacterium
Sponsors
Heat Biologics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Safety and Tolerability | Up to 3 years. | To evaluate the safety and tolerability of vesigenurtacel-L |
| Phase 2: 1-year Disease-Free Survival | One year | Arm 1, 2, 3: 1-year DFS in patients with NMIBC treated with BCG in combination with blinded study product (one of two doses of vesigenurtacel-L or placebo) Arm 4: 1-year DFS in patients with NMIBC treat1fv 9 with high dose vesigenurtacel-L monotherapy One-year disease-free survival will be defined as the proportion of patients who are free from recurrent disease, progressive disease, and alive one year after the date of randomization/treatment assignment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall Disease-free Survival | Up to 3 years | Evaluate overall Disease Free Survival |
| Overall Survival, Expressed as the Number of Participants Alive | Up to 3 years | Evaluate overall survival (OS) |
| Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months | Up to 2 years | — |
| 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 |
| Immunologic Response of PBMCs Via Intracellular Cytokine Staining (ICS) by Flow Cytometry and/or Enzyme-linked Immunosorbent Spot (ELISPOT) on CD8+ Cells After HS-410 Vaccination as Compared to Baseline. | Up to 2 years | Evaluate the proportion of patients with immunologic response of peripheral blood mononuclear cells (PBMCs) via intracellular cytokine staining (ICS) by flow cytometry and/or ELISPOT on CD8+ cells following vesigenurtacel-L vaccination |
| Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | Up to 2 years | Evaluate the proportion of patients with recurrence at 3, 6, 12, 18, and 24 months |
| 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) |
| Tumor Antigen Expression | At screening | Evaluation of pre-treatment tumor tissue for antigen expression |
| Tumor Infiltrating Lymphocytes (TILs) | Up to 3 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 Treatment | Up to 2 years | Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs, T cell receptor sequencing of peripheral blood T cells before and during the course of treatment. |
| Safety of the Combination of the HS-410 and BCG | Up to 1 year | Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG |
| Safety of the High Dose HS-410 Monotherapy | Up to 3 years. | Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy |
| 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) |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 | 10 |
| 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.
HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
BCG: Vaccine derived from a live bacterium | 26 |
| 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.
HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96
BCG: Vaccine derived from a live bacterium | 26 |
| 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.
Placebo: Injection containing sterile solution but no cells
BCG: Vaccine derived from a live bacterium | 26 |
| 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.
HS-410: Vaccine derived from irradiated cancer cells genetically engineered to continually secrete gp96 | 16 |
| Total | 104 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 19 Participants | 14 Participants | 20 Participants | 15 Participants | 77 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 7 Participants | 12 Participants | 6 Participants | 1 Participants | 27 Participants |
| Age, Continuous | 73.2 years STANDARD_DEVIATION 7.495 | 70.5 years STANDARD_DEVIATION 11.176 | 68.58 years STANDARD_DEVIATION 11.518 | 70.58 years STANDARD_DEVIATION 9.047 | 72.50 years STANDARD_DEVIATION 9.784 | 70.60 years STANDARD_DEVIATION 10.172 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 25 Participants | 24 Participants | 24 Participants | 16 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 26 Participants | 25 Participants | 23 Participants | 16 Participants | 100 Participants |
| Region of Enrollment United States | 10 participants | 26 participants | 26 participants | 26 participants | 16 participants | 104 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 5 Participants | 6 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Male | 9 Participants | 23 Participants | 21 Participants | 20 Participants | 13 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 16 |
| other Total, other adverse events | 7 / 10 | 24 / 26 | 19 / 26 | 20 / 26 | 9 / 16 |
| serious Total, serious adverse events | 0 / 10 | 8 / 26 | 4 / 26 | 1 / 26 | 2 / 16 |
Outcome results
Primary
Phase 1: Safety and Tolerability
To evaluate the safety and tolerability of vesigenurtacel-L
Time frame: Up to 3 years.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: HS-410 Low Dose | Phase 1: Safety and Tolerability | Gastrointestinal Disorders | 3 Participants |
| Phase I: HS-410 Low Dose | Phase 1: Safety and Tolerability | General Disorders & Administration Site Conditions | 5 Participants |
| Phase I: HS-410 Low Dose | Phase 1: Safety and Tolerability | Musculoskeletal & Connective Tissue Disorders | 1 Participants |
Primary
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: HS-410 Low Dose | Phase 2: 1-year Disease-Free Survival | 7 Participants |
| Phase II: High-Dose HS-410 Plus BCG | Phase 2: 1-year Disease-Free Survival | 9 Participants |
| Phase II: Placebo Plus BCG | Phase 2: 1-year Disease-Free Survival | 6 Participants |
| Phase II: High-Dose HS-410 | Phase 2: 1-year Disease-Free Survival | 12 Participants |
Secondary
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: HS-410 Low Dose | Disease-free Survival at 3, 6, 18, and 24 Months | 18 months | 17 participants |
| Phase I: HS-410 Low Dose | Disease-free Survival at 3, 6, 18, and 24 Months | 6 months | 19 participants |
| Phase I: HS-410 Low Dose | Disease-free Survival at 3, 6, 18, and 24 Months | 24 months | 13 participants |
| Phase I: HS-410 Low Dose | Disease-free Survival at 3, 6, 18, and 24 Months | 12 months | 18 participants |
| Phase I: HS-410 Low Dose | Disease-free Survival at 3, 6, 18, and 24 Months | 3 months | 22 participants |
| Phase II: High-Dose HS-410 Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 12 months | 17 participants |
| Phase II: High-Dose HS-410 Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 18 months | 16 participants |
| Phase II: High-Dose HS-410 Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 24 months | 14 participants |
| Phase II: High-Dose HS-410 Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 6 months | 19 participants |
| Phase II: High-Dose HS-410 Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 3 months | 19 participants |
| Phase II: Placebo Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 12 months | 21 participants |
| Phase II: Placebo Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 3 months | 23 participants |
| Phase II: Placebo Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 6 months | 22 participants |
| Phase II: Placebo Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 18 months | 15 participants |
| Phase II: Placebo Plus BCG | Disease-free Survival at 3, 6, 18, and 24 Months | 24 months | 12 participants |
| Phase II: High-Dose HS-410 | Disease-free Survival at 3, 6, 18, and 24 Months | 18 months | 2 participants |
| Phase II: High-Dose HS-410 | Disease-free Survival at 3, 6, 18, and 24 Months | 6 months | 9 participants |
| Phase II: High-Dose HS-410 | Disease-free Survival at 3, 6, 18, and 24 Months | 3 months | 14 participants |
| Phase II: High-Dose HS-410 | Disease-free Survival at 3, 6, 18, and 24 Months | 12 months | 4 participants |
| Phase II: High-Dose HS-410 | Disease-free Survival at 3, 6, 18, and 24 Months | 24 months | 1 participants |
Secondary
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
Population: Data were not collected as pre-specified in Outcome Measure 10 due to study termination by the Sponsor.
Secondary
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
Population: Data were not collected as pre-specified in Outcome Measure 11 due to study termination by the Sponsor.
Secondary
Overall Disease-free Survival
Evaluate overall Disease Free Survival
Time frame: Up to 3 years
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: HS-410 Low Dose | Overall Disease-free Survival | 18 participants |
| Phase II: High-Dose HS-410 Plus BCG | Overall Disease-free Survival | 17 participants |
| Phase II: Placebo Plus BCG | Overall Disease-free Survival | 18 participants |
| Phase II: High-Dose HS-410 | Overall Disease-free Survival | 3 participants |
Secondary
Overall Survival, Expressed as the Number of Participants Alive
Evaluate overall survival (OS)
Time frame: Up to 3 years
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: HS-410 Low Dose | Overall Survival, Expressed as the Number of Participants Alive | 26 participants |
| Phase II: High-Dose HS-410 Plus BCG | Overall Survival, Expressed as the Number of Participants Alive | 26 participants |
| Phase II: Placebo Plus BCG | Overall Survival, Expressed as the Number of Participants Alive | 26 participants |
| Phase II: High-Dose HS-410 | Overall Survival, Expressed as the Number of Participants Alive | 16 participants |
Secondary
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: HS-410 Low Dose | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 12 Months | 0 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 24 Months | 1 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 24 Months | 0 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 12 Months | 0 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 24 Months | 0 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 12 Months | 0 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 12 Months | 1 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients Undergoing Cystectomy by 12 and 24 Months | 24 Months | 1 participants |
Secondary
Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months
Time frame: Up to 2 years
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: HS-410 Low Dose | Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months | 12 Month | 8 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months | 24 Months | 8 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months | 12 Month | 6 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months | 24 Months | 7 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months | 12 Month | 10 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months | 24 Months | 11 participants |
Secondary
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: HS-410 Low Dose | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 18 Months | 2 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 3 Months | 1 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 24 Months | 2 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 12 Months | 2 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 6 Months | 2 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 12 Months | 3 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 18 Months | 3 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 6 Months | 3 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 24 Months | 3 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 3 Months | 1 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 12 Months | 1 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 3 Months | 0 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 6 Months | 0 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 24 Months | 2 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 18 Months | 2 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 24 Months | 4 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 18 Months | 4 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 6 Months | 3 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 12 Months | 3 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months | 3 Months | 0 participants |
Secondary
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: HS-410 Low Dose | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 3 months | 22 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 18 months | 18 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 6 months | 19 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 24 months | 14 participants |
| Phase I: HS-410 Low Dose | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 12 months | 18 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 24 months | 14 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 3 months | 19 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 6 months | 19 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 18 months | 16 participants |
| Phase II: High-Dose HS-410 Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 12 months | 17 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 24 months | 12 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 12 months | 21 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 18 months | 15 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 3 months | 23 participants |
| Phase II: Placebo Plus BCG | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 6 months | 22 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 3 months | 14 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 18 months | 2 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 12 months | 4 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 24 months | 1 participants |
| Phase II: High-Dose HS-410 | Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months | 6 months | 9 participants |
Secondary
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
Population: Data were not collected as pre-specified in Outcome Measure 16 due to study termination by the Sponsor.
Secondary
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.
Population: Data were not collected as pre-specified in Outcome Measure 17 due to study termination by the Sponsor.
Secondary
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
Population: Data were not collected as pre-specified in Outcome Measure 15 due to study termination by the Sponsor.
Secondary
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
Population: Data were not collected as pre-specified in Outcome Measure 12 due to study termination by the Sponsor.
Secondary
Tumor Antigen Expression
Evaluation of pre-treatment tumor tissue for antigen expression
Time frame: At screening
Population: Data were not collected as pre-specified in Outcome Measure 13 due to study termination by the Sponsor.
Secondary
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
Population: Data were not collected as pre-specified in Outcome Measure 14 due to study termination by the Sponsor.