2022 The results of AACRCG0070 combined with pembrolizumab in the treatment of non-muscle invasive bladder cancer in stage II are encouraging

Introduction The 2022 American Association for Cancer Research Annual Meeting (AACR) will be held online from 4.
8-4.
13 local time
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As one of the largest cancer research conferences in the world, AACR brings together oncology research and clinical progress from around the world
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One of the phase II, single-arm studies of CG0070 in combination with pembrolizumab in non-muscle-invasive bladder cancer (NMIBC) patients who did not respond to Bacille Calmette-Guerin (BCG) has published preliminary data, let's take a look
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Background CG0070 is a genetically modified adenovirus type 5 (Ad5) oncolytic virus that expresses GM-CSF and can selectively replicate in tumor cells deficient in RB regulation
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The mechanism of action of CG0070 includes targeted lysis of tumor cells and expression of GM-CSF to promote immunogenic cell death
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In an open-label phase II study, patients with high-risk NMIBC who had previously received BCG had an overall complete response (CR) rate of 62% and a 12-month CR rate of 29%
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The US FDA approved intravenous pembrolizumab for the treatment of BCG-unresponsive patients with bladder carcinoma in situ (CIS, with or without papilloma), with an overall CR rate of 41% and a 12-month CR rate of 20%
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This phase II study will evaluate the potential synergistic effects of these two drugs in the treatment of BCG-unresponsive NMIBC patients
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 Figure 1 Mechanism of action of CG0070 A total of 35 patients with BCG non-response, CIS, with or without Ta or T1 disease received intravesical infusion of CG0070 (1×1012vp) combined with intravenous pembrolizumab (400mg/6 weeks)
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Patients first received CG0070 once a week for a total of 6 induction doses; then at 3, 6, 9, 12, and 18 months, they received CG0070 maintenance therapy (once a week, a total of 3 times)
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Patients with CIS or high-grade (HG) Ta may need to re-induction therapy with CG0070 once a week for a total of 6 times at 3 months
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Pembrolizumab was used for up to 24 months
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Efficacy assessments included cystoscopy every 3 months, biopsy of suspicious areas, urine cytology, CTU/MRU, and mandatory bladder biopsy at 12 months
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HG disease recurrence is considered a disease recurrence
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The primary study endpoint was CR at 12 months
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Secondary endpoints included CR at any time, progression-free survival, duration of response, survival after cystectomy, and safety of combination therapy
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Relevant assessments include alterations in the tumor immune microenvironment, induction of systemic immunity, viral replication, and expression of transgenes
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PD-L1 expression, coxsackievirus adenovirus receptor, E2F transcription factor, and anti-Ad5 antibody titers at baseline correlated with tumor response
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Figure 2 Results of study design A total of 18 patients had an overall CR rate of 88.
9% (16/18) at 3 months and 75% (6/8) at 12 months
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Figure 3.
Patient response.
Treatment-related adverse events are limited to grade 1-2 localized genitourinary adverse events, and no grade 3 or 4 treatment-related adverse events have been reported
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Figure 4 Conclusion of treatment-related adverse events The preliminary efficacy and safety data of the combination of CG0070 and pembrolizumab in BCG-unresponsive NMIBC patients are encouraging
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The follow-up results of the study are worth looking forward to
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Reference: Roger Li, Gary Steinberg, Paras Shah et al.
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).
AACR Annual Meeting .
CT036.
Editor: LR Reviewer: Mia Execution: LR