MP54-03: CORE1: Phase 2, Single Arm Study of CG0070 Combined with Pembrolizumab in Patients with Non Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG)

Roger Li*, Tampa, FL, Gary Steinberg, New York, NY, Donald Lamm, Phoenix, AZ, Ed M. Uchio, Orange, CA, Paras Shah, Rochester, MN, Ashish M. Kamat, Houston, TX, Nataliya Hnat, Irvine, CA, Michael J. Chisamore, Kenilworth, NJ, Paola Grandi, James Burke, Irvine, CA

Introduction: CG0070, is an Ad5-based oncolytic vaccine engineered to express GM-CSF and replicate selectively in tumor cells with mutated or deficient RB. The CG0070 mechanism of action includes cell lysis and immunogenic cell death which is enhanced in the presence of GM-CSF. In an open label ph. 2 study, an overall CR rate of 62% and a CR at 12 months (m) of 29% have been observed in pts with high risk NMIBC previously treated with BCG.IV pembrolizumab was recently approved by the FDA for patients with BCG-unresponsive CIS (with or without papillary tumors) with an overall complete RR of 41% and a 12 m CR rate of ~20%.  This ph. 2 study will assess the potential synergy of the two agents in the treatment of BCG-unresponsive NMIBC

Methods: 35 pts with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravesical CG0070 (1x1012 vp) in combination with pembrolizumab at a dose of 400 mg IV q6 weeks. CG0070 will be administered weekly x 6 as induction followed by weekly x 3 maintenance instillations at months 3, 6, 9, 12, and 18. Pts with persistent CIS or HG Ta at 3 m may receive re-induction with weekly x 6 of CG0070. Pembrolizumab will be administered up to 24 m. Assessment of response will include q 3 m cystoscopy with biopsy of areas suspicious for disease, urine cytology, CTU/MRU, and mandatory bladder mapping biopsies at 12 m. Recurrence of HG disease will be enumerated as disease recurrence.

The primary endpoint of the study is CR at 12 m. Secondary endpoints will include CR at any time, progression free survival, duration of response, cystectomy free survival and the safety of the combination. Correlate assessments will include changes in the tumor immune microenvironment, systemic immune induction, viral replication and transgene expression. Baseline expression of PD-L1, coxsackie adenovirus receptor, E2F transcription factor as well as anti-Ad5 Ab titer will be correlated with tumor response.

Results: 9 pts have reached the 3 m follow up time point with all 9 achieving a CR (100% CR rate).  Of these, 6 pts have reached the 6 m and 3 pts the 9 m landmarks with a CR achieved at all timepoints.  Treatment related AE have been limited to transient grade 1-2 urinary frequency.   No treatment-related grade 3 or higher AE or SAE have been observed.

Conclusions: The combination of CG0070 and pembrolizumab has been well tolerated with encouraging early efficacy data. An update on this ongoing trial will be provided at the time of presentation.

Source of Funding: CG Oncology