AACR 2022: 100% CR rate in 3 months!

CG0070 is an engineered adenovirus type 5 (Ad5) oncolytic virus drug developed by CG Oncology

In the BOND2 trial, CG0070 achieved significantly better CR than drug K, the 3-month CR rate of CG0070 was 46.

A total of 35 BCG-unresponsive CIS patients (with or without Ta or T1 disease) received intravesical CG0070 (1x10 ¹² vp) combined with intravenous pembrolizumab (400 mg IV, q6w)

Efficacy assessments will include cystoscopy every 3 months, biopsy of suspicious lesions, urine cytology, CTU/MRU, and mandatory bladder mapping biopsy at 12 months

The primary endpoint of this study was CR at 12m

RESULTS: So far, 10 patients can be evaluated for efficacy at 3 months

Treatment-related adverse events were limited to transient grade 1-2 local genitourinary adverse events, and no grade 3 or 4 treatment-related adverse events were reported

Conclusions: Preliminary data on the efficacy and safety of CG0070 in combination with pembrolizumab in BCG-unresponsive NMIBC are encouraging

▌ References:

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).

Bladder cancer is one of the common malignant tumors in urology

At present, the treatment methods for NMIBC are very limited.

CG0070 is an engineered adenovirus type 5 (Ad5) oncolytic virus drug developed by CG Oncology
.
CG0070 is based on an engineered adenovirus type 5 (Ad5) backbone, including a tumor-specific promoter E2F-1 and a granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene, with the modified Ad5 selectable It replicates in tumor cells deficient in Rb regulation and eventually lyses tumor cells
.
The ruptured cancer cells will further release tumor antigens and GM-CSF, stimulate the systemic anti-tumor immune response, and achieve the dual effects of cytolysis and enhanced immunogenic cell death
.

On November 13, 2021, CG Oncology disclosed the very eye-catching phase II clinical trial data of its oncolytic virus drug CG0070 combined with K drug
.
Results of the trial showed that of 9 patients with non-muscle-invasive bladder cancer (NMIBC) who were evaluable for efficacy in non-muscle invasive bladder cancer (NMIBC) non-responsive to BCG The CR rate of patients at the monthly and 9-month assessment nodes also remained at 100%
.

In the BOND2 trial, CG0070 achieved significantly better CR than drug K, the 3-month CR rate of CG0070 was 46.
2% (40.
6% in the K drug group), and the 12-month CR rate was 29.
2% (18.
7% in the K drug group)
.
The FDA recently approved intravenous pembrolizumab for the treatment of patients with Bacille Calmette-Guerin (BCG) unresponsive bladder carcinoma in situ (CIS, with or without papillary tumors), with an overall complete RR of 41% for pembrolizumab,12 The monthly CR rate is about 20%
.
This phase 2 study (CORE1) will evaluate the potential synergy of the two drugs in the treatment of BCG-unresponsive NMIBC
.

A total of 35 BCG-unresponsive CIS patients (with or without Ta or T1 disease) received intravesical CG0070 (1x10 ¹² vp) combined with intravenous pembrolizumab (400 mg IV, q6w)
.
The usage of CG0070 is as follows: induction perfusion is performed first, that is, once a week for a total of 6 times; then maintenance perfusion is performed at 3, 6, 9, 12 and 18 months, that is, once a week for a total of 3 times
.
Patients with persistent CIS or high-grade Ta lesions (HG-Ta) at 3 months received weekly reinduction with CG0070 for a total of 6 times
.
Pembrolizumab can be used for up to 24 months
.

Efficacy assessments will include cystoscopy every 3 months, biopsy of suspicious lesions, urine cytology, CTU/MRU, and mandatory bladder mapping biopsy at 12 months
.
A recurrence of HG disease will be considered a disease recurrence
.

The primary endpoint of this study was CR at 12m
.
Secondary endpoints included CR at any time, progression-free survival, duration of response, cystectomy-free survival, and safety of the combination
.
Relevant assessments will include changes in the tumor immune microenvironment, induction of systemic immunity, viral replication, and transgene expression
.
Correlation of baseline expression of PD-L1, coxsackie adenovirus receptor, E2F transcription factor, and anti-Ad5 antibody titers with tumor response
.

RESULTS: So far, 10 patients can be evaluated for efficacy at 3 months
.
Evaluation of these 10 patients showed a 100% CR rate at 3 months
.
Of these 10 patients, 6 maintained CR at 6 months and 2 maintained CR at 12 months
.

Treatment-related adverse events were limited to transient grade 1-2 local genitourinary adverse events, and no grade 3 or 4 treatment-related adverse events were reported
.

Conclusions: Preliminary data on the efficacy and safety of CG0070 in combination with pembrolizumab in BCG-unresponsive NMIBC are encouraging
.

Domestic Lepu Bio has the authorization to develop, manufacture and commercialize this product in China
.
A few days ago (November 12, 2021), Lepu Bio has also obtained the domestic clinical approval and has been approved to conduct clinical trials for non-muscle invasive bladder cancer
.
(CG0070 is the world's first and only oncolytic virus product in Phase III clinical stage for the treatment of NMIBC)

Lepu Bio is also currently planning to initiate a clinical trial of CG0070 in combination with its core product HX008 for advanced NMIBC patients (Putlimumab (HX008) is an anti-PD-1 monoclonal antibody product of Lepu Bio, which The new drug marketing application for the treatment of melanoma and MSI-H/dMMR solid tumors has been accepted by the State Food and Drug Administration, and the marketing application for MSI-H/dMMR solid tumors was officially included in priority review by CDE on November 4, 2021 )
.
In addition to bladder cancer, Lepu Bio also plans to further develop CG0070Other indication areas such as colorectal cancer , liver cancer and breast cancer
.

▌ References:

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).
AACR 2022.
abstr.
CT036