Innovent Biologics presented Phase I clinical data for the monotherapy of solid tumors with IBI351 (KRAS G12C inhibitor) at the 2022 Chinese Society of Clinical Oncology (CSCO) Annual Meeting

Innovent Biopharmaceutical Group (^HKEx stock code: 01801), a biopharmaceutical company dedicated to the development, production and sales of innovative drugs in the field of major diseases such as oncology, autoimmunity, metabolism, ophthalmology, etc.
, presented an oral presentation at the 2022 Chinese Society of Clinical Oncology (CSCO) Annual Meeting (NCT05005234) in the form of an oral report (NCT05005234) The result of the update
.

Report: Update on Phase IA study results of IBI351 monotherapy in patients with advanced solid tumors

IBI351 (GFH925), a specific covalent and irreversible inhibitor of KRAS G12C, is a Phase I clinical study to evaluate the safety, tolerability, and preliminary efficacy
of IBI351 monotherapy in subjects with advanced malignancies who have failed or intolerated standard therapy and have KRAS^G12C mutations 。 As of July 29, 2022, a total of 67 subjects with advanced malignancy who had previously failed or were intolerant to standard therapy were enrolled in this study, including 61 cases of non-small cell lung cancer, 5 cases of bowel cancer, and 1 case of pancreatic cancer
.
Nearly 50% of the subjects had previously received 2 lines or more of treatment, and 37.
7% of lung cancer patients had brain metastases
at baseline.

The results of the study showed:

● Among the 55 patients with non-small cell lung cancer whose efficacy could be assessed, the objective response rate (ORR) was 50.
9% and the disease control rate (DCR) was 92.
7%.

The vast majority of patients in remission are still on ongoing treatment
.
Sustained tumour remission was shown in the low-dose group, with a maximum duration of 8.
9 months (450 mg QD dose), and ongoing treatment
.
Neither the median duration of response nor the median progression-free survival were achieved
.

● The 600mg BID dose group (RP2D recommended dose) showed better efficacy, with objective response rates (ORR) and disease control rates (DCRs) of 61.
9% (13/21) and 100%
respectively in 21 evaluable subjects.

● A total of 5 subjects with advanced colorectal cancer received IBI351 treatment, of which 3 subjects achieved partial remission, with an objective response rate (ORR) and disease control rate (DCR) of 60%.

One pancreatic cancer subject achieved partial remission at the first tumor evaluation and was still on treatment before the deadline
.

● In terms of safety, as of the date of data analysis, the overall tolerability was good, no DLT events were observed in each dose group, and MTD was not reached
.
A total of 92.
5% (62/67) of participants experienced drug-related adverse events (TRAEs), mostly grade 1 to 2, with the most common TRAE being anemia, elevated aminotransferases, elevated bilirubin, pruritus, and fatigue
.
Grade ≥3 TRAEs occurred in 19.
4% of participants, with no TRAEs leading to death or treatment termination
.

IBI351 monotherapy has demonstrated good safety, tolerability and encouraging efficacy signals in patients with advanced lung, colorectal and pancreatic cancer with KRAS^G12C mutations who have failed or are intolerant to previous standard therapy
.
The single-arm registration study of IBI351 monotherapy for advanced non-small cell lung cancer carrying the KRAS^G12C mutation is ongoing, and relevant clinical results will be presented
at future medical meetings.

Professor Wu Yilong of Guangdong Provincial People's Hospital said: "As one of the earliest oncogenes discovered, KRAS has become a hot direction
for research and development.
IBI351 (GFH925), a specific covalent and irreversible KRAS^G12C inhibitor, presented preliminary efficacy and safety data
at this year's ASCO Annual Meeting.
The results updated at this CSCO conference further demonstrate that IBI351 (GFH925) monotherapy has demonstrated a good safety profile and encouraging efficacy
in advanced solid tumors with KRAS^G12C mutation.
We look forward to more positive and ongoing updates on the results of this study
.
"

Dr.
Hui Zhou, Senior Vice President, Innovent Biopharmaceutical Group, said, "We are pleased to share the updated results of the IBI351 clinical development program at this year's CSCO Annual Meeting, IBI351 monotherapy has shown encouraging efficacy and safety signals in Phase Ia clinic, single-arm registration studies for advanced non-small cell lung cancer with KRAS^G12C mutations are ongoing, and we look forward to advancing monotherapy and combination therapies of this high-potential molecule in lung cancer, pancreatic cancer, and Further development
in the field of high-incidence cancers such as colorectal cancer.
As immuno-oncology enters the next level, we will continue to uphold our mission of developing high-quality biologic drugs that are affordable to the public to benefit more patients
in need.
"

About IBI351/GFH925 (KRAS^G12C inhibitor)

As a highly effective oral novel molecular entity compound, IBI351 effectively inhibits the protein-mediated GTP/GDP exchange by covalently and irreversibly modifying cysteine residues of KRAS^G12C protein mutants, thereby downregulating the activation level of KRAS protein.
Preclinical cysteine selectivity testing also showed the high selective inhibition of IBI351 for this mutation site
.
In addition, IBI351 can inhibit the downstream signaling pathway after inhibiting KRAS protein, effectively inducing tumor cell apoptosis and cell cycle arrest, and achieving anti-tumor effect
.

In September 2021, Innovent and GenFleet announced a global exclusive licensing agreement under which Innovent acquired the development and commercialization rights of GFH925 (Innovent R&D code: IBI351) in China (including Chinese mainland, Hong Kong, Macau and Taiwan) as an exclusive partner, with the option of global development and commercialization rights
.