Innovent Presents at the 2024 ASCO Annual Meeting on Clinical Data of anti-CLDN18.2 ADC (IBI343) in Patients with Advanced Pancreatic Cancer or Biliary Tract Cancer

Rhea-AI Summary

Innovent Biologics presented Phase 1 clinical data of IBI343 (TOPOi anti-CLDN18.2 ADC) for advanced pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) at the 2024 ASCO Annual Meeting. The study involved 35 patients, with 25 undergoing at least one post-baseline tumor evaluation. Results showed a 28% objective response rate (ORR) and an 80% disease control rate (DCR). In the 6 mg/kg dose group, the ORR was 38.5% and DCR was 84.6%. Treatment-related adverse events (TRAEs) affected 80% of subjects, with anemia being the most common. No TRAEs led to death.

Positive

• IBI343 showed a 28% objective response rate (ORR) in patients with PDAC and BTC.
• The disease control rate (DCR) was high at 80%.
• Specifically, in the 6 mg/kg dose group, the ORR was 38.5% and DCR was 84.6%.
• No treatment-related adverse events (TRAEs) led to death.
• IBI343 showed a promising safety profile, with only 25.7% of participants developing grade 3 or higher TRAEs.
• The trial indicated potential for IBI343 as a second-line treatment where options are

Negative

• 80% of subjects experienced treatment-related adverse events (TRAEs).
• Common TRAEs included anemia (42.9%), neutrophil count decreased (28.6%), nausea (25.7%), vomiting (25.7%), and white blood cell count decreased (22.9%).
• 25.7% of participants developed grade 3 or higher TRAEs.
• Disease control and overall survival data are not yet mature.
• The clinical benefit is based on preliminary Phase 1 data, which may not predict long-term outcomes.

SAN FRANCISCO, U.S. and SUZHOU, China , June 1, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, presented Phase 1 clinical data of IBI343 (TOPOi anti-CLDN18.2 ADC) for the treatment of advanced pancreatic ductal adenocarcinoma or biliary tract cancer at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (NCT05458219). In addition, clinical data of the treatment for advanced gastric or gastroesophageal tumors from this Phase 1 trial will be published in oral presentation at the ESMO Gastrointestinal Cancers Congress 2024 this month.

Dr. Hui Zhou, Senior Vice President of Innovent Biologics, said, "We are excited to share the latest clinical development updates on IBI343 at ASCO. As an innovative TOPOi ADC, IBI343 showed a positive clinical signal in subjects with advanced pancreatic cancer and the incidence of grade 3 or above gastrointestinal adverse events is low. It is the first CLDN18.2 ADC to achieve a breakthrough in this difficult-to-treat cancer and shed light on the exploring directions to this therapeutic field. We will continue to follow up on the clinical data update of IBI343. As one of the few biopharmaceutical companies with leading R&D capabilities in both immunotherapy (IO) and antibody-drug conjugates (ADCs), we will also explore combination therapy of IBI343 and its therapeutic potential in other solid tumors such as gastric cancer for the benefit of more patients."

Safety and efficacy of IBI343 (anti-CLDN18.2 ADC) in patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer: preliminary results from a Phase I study

Abstract#:3037

This Phase I study is conducted in China and Australia, aiming to evaluate the safety, tolerability and preliminary efficacy of IBI343 in subjects with advanced solid tumors. Data on patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer were presented at this congress. As of December 19, 2023, a total of 35 patients with advanced pancreatic ductal adenocarcinoma (PDAC) or biliary tract cancer (BTC) were enrolled, and all subjects had received at least one prior systemic treatment, with a median of 2 lines of treatment.

The results showed that:

• As of January 15, 2024, 25 subjects had performed at least one post-baseline tumor evaluation. 7 subjects achieved partial response (PR), 5 of which were PDAC patients, 2 were BTC patients. The objective response rate (ORR) was 28.0% (95% CI: 12.1-49.4), and the disease control rate (DCR) was 80.0% (95% CI: 59.3-93.2).
• In the 6 mg/kg dose group, 13 subjects with CLDN18.2 1/2/3+≥60% had at least one post-baseline tumor assessment, of which 5 achieved PR with an ORR of 38.5% (95%CI: 13.9-68.4) and a DCR of 84.6% (95% CI：54.6-98.1).  Among the 10 subjects with advanced PDAC in this subgroup, the ORR was 40% (95% CI: 12.2-73.8). DoR and PFS data are not mature yet.
• In terms of safety, 80.0% of subjects experienced treatment-related adverse events (TRAEs). Common TRAEs were anemia (42.9%), neutrophil count decreased (28.6%), nausea (25.7%), vomiting (25.7%) and white blood cell count decreased (22.9%). 25.7% of participants developed ≥ grade 3 TRAEs. No TRAE led to death.

Professor Xianjun Yu, Fudan University Shanghai Cancer Center, said: "Advanced pancreatic cancer and biliary tract cancer progress rapidly while the clinical course is initially insidious. Most patients are often not diagnosed until advanced stages with poor prognosis. Currently, chemotherapy remains a mainstay of the first-and-second line treatments for advanced pancreatic cancer and bile duct cancer. The clinical options for second-line treatment are particularly limited and cannot bring significant clinical benefits to patients. FOLFOX is used as a second-line standard of care for advanced biliary tract cancer with an ORR of 5%, a median overall survival OS of 6.2 months ^[1]. In the second-line treatment of pancreatic cancer, the response rate to chemotherapy is only 6%~16%, and the median survival time is only about 3~6 months ^[2].

CLDN18.2 has become a promising target for the treatment of patients with digestive malignancies, which has a high expression rate in pancreatic cancer and biliary tract cancer. The expression rate in pancreatic cancer patients is 50%~70% ^[3], and 52% of biliary tract cancer ^[4]. Promising clinical benefit of the novel TOPOi anti-CLDN18.2 ADC IBI343 has been observed in subjects with advanced pancreatic cancer and biliary tract cancer. Particularly in advanced pancreatic cancer participants with high CLDN18.2 expression, it showed encouraging efficacy signals and a tolerable safety profile, which may bring patients novel and effective treatment options."

About IBI343（Anti CLDN18.2 ADC）

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization will occur and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect".

As an innovative TOPOi ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in this phase I clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric cancer and pancreatic cancer. In May 2024, The National Medical Products Administration (NMPA) of China granted breakthrough therapy designation (BTD) to IBI343 for use as a single agent in patients with claudin 18.2–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who experienced disease progression following 2 prior lines of systemic treatment. The multi-center Phase 3 trial of IBI343 for this indication is in preparation.

About Innovent Biologics

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 10 products in the market. It has 4 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, 'Start with Integrity, Succeed through Action,' Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Disclaimer: Innovent does not recommend any unapproved drugs/indications.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics, Inc. ("Innovent" or "Company"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

References

[1]	Lamarca A, Palmer DH, Wasan HS, et al. Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May; 22(5):690-701.
[2]	Vaccaro V, Sperduti I, Vari S, et al. Metastatic pancreatic cancer: Is there a light at the end of the tunnel?. World J Gastroenterol. 2015; 21(16):4788-4801.
[3]	Wu YY, Fan L, Liao XH, et al. Claudin 18.2 is a potential therapeutic target for zolbetuximab in pancreatic ductal adenocarcinoma. World J Gastrointest Oncol. 2022 Jul 15; 14(7):1252-1264.
[4]	Yan P, Dong Y, Zhang F, Zhen T, Liang J, Shi H, Han A. Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts. J Clin Pathol. 2024 Mar 28:jcp-2023-209268.

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SOURCE Innovent Biologics

FAQ

What were the results of Innovent's IBI343 Phase 1 trial presented at ASCO 2024?

The Phase 1 trial of IBI343 for advanced pancreatic ductal adenocarcinoma and biliary tract cancer showed a 28% objective response rate and 80% disease control rate. In the 6 mg/kg dose group, the ORR was 38.5%.

What is the significance of IBI343's 28% objective response rate?

The 28% ORR indicates that 7 out of 25 evaluated patients experienced a reduction in tumor size, suggesting potential efficacy for IBI343 in treating advanced pancreatic and biliary tract cancers.

What adverse events were observed in the IBI343 Phase 1 trial?

80% of subjects experienced treatment-related adverse events, with the most common being anemia (42.9%), decreased neutrophil count (28.6%), nausea (25.7%), vomiting (25.7%), and decreased white blood cell count (22.9%).

How effective was IBI343 in high CLDN18.2 expression pancreatic cancer patients?

In the 6 mg/kg dose group, 40% of advanced PDAC patients with high CLDN18.2 expression achieved a partial response.

What were the disease control and objective response rates for the 6 mg/kg dose group in the IBI343 trial?

In the 6 mg/kg dose group, the objective response rate was 38.5%, and the disease control rate was 84.6%.

What is the safety profile of IBI343 based on the Phase 1 trial?

While 80% of subjects experienced treatment-related adverse events, no TRAEs led to death, and only 25.7% developed grade 3 or higher TRAEs, indicating a tolerable safety profile.

What further research is needed for IBI343?

Additional research is needed to mature the duration of response and progression-free survival data to confirm the long-term efficacy and safety of IBI343.