On January 4, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI351 (GFH925) for the treatment of advanced non-small cell lung cancer patients with KRASG12C mutation that have received at least one prior line of systemic therapy (Press release, Innovent Biologics, JAN 4, 2023, View Source [SID1234625839]).

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The NMPA BTD for IBI351 was based on the results from a phase I/II trial (CDE Registration No. CTR20211933). This study aims to evaluate the safety, tolerability and efficacy of IBI351 monotherapy in patients with advanced solid tumors who failed or intolerant to standard of care treatment.

The latest results of IBI351 from the phase I study were presented at the 2022 Chinese Society of Clinical Oncology (CSCO) Annual Meeting. As data cutoff (29 July 2022), of 55 evaluable NSCLC patients, the investigator assessed objective response rate (ORR) was 50.9% and disease control rate (DCR) was 92.7%. Of 21 patients with NSCLC treated at 600mg BID (the recommended phase 2 dose), better efficacy signal was observed, with investigator assessed ORR 61.9% and DCR 100%. Median duration of response (DOR) and median progression free survival (PFS) were not reached yet.

As data cutoff date, IBI351 was well tolerated. No DLT was reported and MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 92.5% (62/67) patients and the most common TRAEs were anemia, transferase increased, bilirubin increased, pruritus and fatigue. The majority of the TRAEs were grade 1-2 with 19.4% (13/67) of patients reporting grade 3 or higher TRAEs. There were no grade 5 TRAEs or TRAEs led to treatment discontinuation.

Favorable safety and tolerability and promising antitumor activity of IBI351 monotherapy were observed. The single-arm registrational trial of IBI351 monotherapy in previously-treated advanced non-small cell lung cancer patients with KRASG12C mutation is ongoing. Relevant updated study results will be published at an upcoming medical conference in 2023.

"We are glad to see the NMPA grants Breakthrough Therapy Designation based on the results of Phase I data of IBI351," said Dr. Hui Zhou, Senior Vice President of Innovent. "KRASG12C mutated NSCLC patients have limited treatment options. IBI351 demonstrated encouraging efficacy and safety data in Phase I study. A single arm registrational trial of IBI351 monotherapy in previously-treated advanced NSCLC is ongoing. We are working to advance into late stage clinical development to explore the potential of IBI351 as monotherapy and in combo-therapy."

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify a drug candidate to receive status for rapid review by the CDE, but it will also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace. Click here for the published list of drugs which have been granted BTD by NMPA.

About Non-small Cell Lung Cancer

Lung cancer is one of the malignancies with the highest incidence and mortality worldwide, among which non-small cell lung cancer (NSCLC) is the most common pathological type, accounting for about 85% of all lung cancers. KRAS mutations are common driver gene mutations in NSCLC, most of which occur in lung adenocarcinoma. KRAS mutations rarely co-exist with driver mutations such as EGFR and ALK, and patients with advanced NSCLC with KRASG12C mutations are often unable to benefit from the multiple drugs already on the market that target these mutations or rearrangements. After the progress of first-line standard treatment in this population, there are limited second-line treatment options with low effective rate and poor prognosis.

About IBI351/GFH925(KRASG12C Inhibitor)

Discovered by GenFleet Therapeutics, GFH925 (Innovent R&D code: IBI351) is a novel, orally active, potent KRASG12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRASG12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of IBI351 towards KRASG12C. Subsequently, IBI351 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.

In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of IBI351 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.