An Expanded Access Program of Cretostimogene Grenadenorepvec for Treatment of NMIBC for Patients Unresponsive to BCG

An Expanded Access Program of Cretostimogene Grenadenorepvec in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG)

This is an open-label, expanded access trial designed to provide access to cretostimogene in patients with NMIBC (specifically CIS with or without HG Ta/T1) unresponsive to BCG.

All participants will be assigned the same treatment schedule. Participants will receive an induction course of 6 weekly treatments, and, if there is no disease recurrence at Week 13, participants will receive a cycle of 3 weekly treatments up to Week 15.

If there is persistent HG Ta and/or CIS at Week 13, participants may receive a second induction cycle.

If the participant has persistent but improved HG Ta and/or CIS at Week 25 or a later timepoint, the participant may receive a cycle of 3 weekly treatments of cretostimogene at the discretion of the Investigator provided that T1 or higher stage of urothelial carcinoma is not present.

If there is no disease present at Week 25 or a later timepoint, participants will receive a cycle of 3 weekly treatments every 12 weeks through Month 12.

After Month 12, participants will receive a cycle of 3 weekly treatments every 6 months through the last treatment cycle at Month 24, or until discontinuation from the study treatment.

Disease status will be assessed based on local standard of care (which may include urine cytology, cystoscopy, and directed TURBT/biopsy) every 12 weeks. CTU/MRU can be done per standard of care evaluation at investigator's discretion.

Inclusion Criteria:

1. Have pathologically confirmed BCG unresponsive CIS. There is no maximum limit to the amount of prior BCG treatment, but maintenance BCG should be administered on a schedule consistent with standard induction-maintenance protocols. Specifically, the definition of BCG unresponsive CIS will also require the following:

   • Pathologically confirmed relapsed or persistent CIS (with or without HG Ta or HG T1 disease)
   • Completion of qualifying BCG treatment (e.g., "5+2" minimum exposure) within 15 months of the initial qualifying dose of BCG.

2. Have all Ta and/or T1 disease and all CIS resected or fulgurated, as feasible, prior to study treatment

3. Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy according to Investigator assessment.

4. Acceptable baseline organ function

Exclusion Criteria:

1. Muscle invasive bladder cancer, locally advanced or metastatic bladder cancer.
2. Has had active autoimmune or inflammatory disease requiring systemic treatment within 4 weeks of Day 1. Replacement therapy is not considered an excluded form of systemic treatment and is allowed.
3. Has received systemic anticancer therapy, including investigational agents, within 4 weeks of Day 1
4. Is pregnant, currently breastfeeding or intending to breastfeed, beginning at Screening through 1 week after the last study treatment.