a phase 1/2 study of hs-410 in patients with non-muscle invasive bladder cancer after turbt

Conditions: Bladder Cancer

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.

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.

Eligibility criteria:
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

Keywords: turbt bladder cancer gp96 vaccine immunotherapy heat biologics bcg bacillus calmette-guerin bacillus calmette-guérin