IBI343 for Cancer

Recruiting at 38 trial locations

Overseen By Suhua Dong

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Must not be taking: CYP3A4 inhibitors, Live vaccines

Disqualifiers: Infections, CNS metastases, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

470 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate a new treatment, IBI343, for individuals with advanced solid tumors that cannot be surgically removed or have metastasized. The primary goal is to assess the treatment's safety and determine the optimal dose for future studies. Potential participants include those with specific cancers such as pancreatic, biliary, or gastric cancer, whose cancer has not responded to standard treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received antineoplastic therapy within 4 weeks or certain other medications like strong CYP3A4 inhibitors within 2 weeks before starting the study drug.

Is there any evidence suggesting that IBI343 is likely to be safe for humans?

Research has shown that IBI343 has a good safety record in clinical studies. These studies found that patients with advanced cancer generally tolerate IBI343 well. For instance, tests on individuals with advanced pancreatic cancer showed positive safety results. Additionally, in patients with a specific type of stomach cancer, IBI343 was well tolerated and demonstrated early signs of effectiveness against the cancer. While side effects can occur, as with any treatment, current data suggest that IBI343 is a promising option for certain types of advanced cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pancreatic cancer, which often involve chemotherapy drugs like gemcitabine and nab-paclitaxel, IBI343 works differently by targeting specific pathways that are crucial for cancer cell survival. Researchers are excited about IBI343 because it offers a novel mechanism of action that could potentially overcome resistance seen with conventional therapies. Additionally, the flexibility in dosing strategies, with phase 1a exploring optimal doses across different regions, allows for tailored treatment approaches that could maximize effectiveness and minimize side effects. This innovative approach offers hope for better outcomes for patients with pancreatic cancer.

What evidence suggests that IBI343 might be an effective treatment for cancer?

Research has shown that IBI343, a new treatment under study in this trial, shows promise in fighting certain cancers. Studies found that, on average, patients went about 6.8 months without their cancer worsening, indicating stability in many patients' conditions during this period. Additionally, IBI343 was generally well-tolerated, causing no severe side effects for most patients. Early results also suggest it could effectively treat advanced pancreatic cancer and some stomach cancers. This data indicates that IBI343 might offer hope for people with these difficult-to-treat cancers. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be surgically removed or have spread, and who don't respond to standard treatments. Participants must have at least one measurable tumor and good organ function. They should agree to use effective contraception.

Inclusion Criteria

My cancer is in the stomach or pancreas and cannot be removed by surgery.

I have an advanced cancer that can't be removed by surgery and standard treatments don't work or aren't suitable for me.

I have at least one tumor that can be measured.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

IBI343 is administered intravenously at different dose levels following accelerated titration and traditional 3+3 dose escalation design

21 days

Multiple visits for dose administration and monitoring

Dose Optimization

IBI343 is administered in parallel cohorts to determine the optimal dose for the PDAC indication

Varies

Regular visits for dose administration and monitoring

Dose Expansion

IBI343 is administered at dose levels equal to or lower than MTD to further evaluate safety and efficacy

Varies

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days after the last administration

What Are the Treatments Tested in This Trial?

Interventions

• IBI343

Trial Overview The study tests IBI343 in patients with specific types of advanced cancer. It's an early-phase trial aiming to find the safest dose with acceptable side effects (MTD) and see how well it works against the cancer.

How Is the Trial Designed?

Group I: Single arm Experimental Treatment 1 Intervention

Phase 1a Part 1 Dose Escalation: IBI343 will be administered intravenously (IV) at different dose levels following traditional 3+3 dose escalation design for following levels. Phase 1a Part 1 Dose Expansion: IBI343 will be administered at dose levels which is equal or lower than MTD. Each dose level contains no more than 30 subjects (including subjects in dose escalation) Phase 1a Part 2 Dose Optimization: IBI343 will be administered in parallel cohorts (randomized 1:1 ratio) to determine the optimal dose for the PDAC indication across China, Australia and the US (n=40). Dose levels 4.5mg/kg and 6mg/kg will be studied. Phase 1b Dose Extension: IBI343 will be administered at RP2D.

Group II: 3 arms Experimental Treatment 3 Interventions

Phase 1a Part 3: For monotherapy: 6 mg/kg Q3W was confirmed as the optimal dosing regimen for balancing clinical benefits and potential risks. In 1L G/GEJ AC and 1L PDAC cohort of the Phase Ia (Part 3) study, IBI343 combination therapy is proposed to be administered at doses of 4 mg/kg (Dose level 1) Q2W or 5 mg/kg (Dose level 2) Q2W in participants with G/GEJ AC and PDAC for the randomized study.

IBI343 is already approved in China for the following indications:

Approved in China as IBI343 for:

• Advanced gastric/gastro-esophageal junction adenocarcinoma

Who Is Running the Clinical Trial?

Innovent Biologics (Suzhou) Co. Ltd.

Lead Sponsor

Trials

184

Recruited

28,300+

Dr. Michael Yu

Innovent Biologics (Suzhou) Co. Ltd.

Chief Executive Officer since 2011

PhD in Molecular Biology

Dr. Nageatte Ibrahim

Innovent Biologics (Suzhou) Co. Ltd.

Chief Medical Officer

MD

Innovent Biologics, Inc.

Collaborator

Trials

7

Recruited

4,400+

TigerMed

Collaborator

Trials

4

Recruited

1,100+

Fortvita Biologics (USA)Inc.

Industry Sponsor

Trials

1

Recruited

80+

TigerMed

Industry Sponsor

Trials

4

Recruited

1,100+

Published Research Related to This Trial

In a study of 473 breast cancer patients, activating mutations in the PIK3CA gene were found in 12.3% of tumors, with a notable increase in mutation frequency as the disease progressed from early to late stages (2.4% to 28.7%).

The presence of these PIK3CA mutations was associated with significantly reduced relapse-free survival, particularly in patients with stage III cancer, indicating their potential role as a negative prognostic factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between the Prevalence of Somatic Mutations in PIK3CA Gene in Tumors and Clinical and Morphological Characteristics of Breast Cancer Patients. Filipenko, ML., Os'kina, NA., Oskorbin, IA., et al.[2022]

Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs) due to their mechanism of action, necessitating a multidisciplinary approach for effective patient management, as highlighted by 30 real-world pharmacovigilance studies.

These studies have provided valuable insights into the patterns, kinetics, and fatality rates of various irAEs, emphasizing the need for oncologists to understand both the strengths and limitations of this data for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance. Raschi, E., Gatti, M., Gelsomino, F., et al.[2021]

A large-scale analysis of 16,196 serious adverse drug reaction reports identified 36 potential safety signals associated with ibrutinib, including ischemic heart diseases and fractures, highlighting the need for careful patient monitoring.

The study found that over half of the reports resulted in hospitalization, indicating that while ibrutinib is a standard treatment for B-cell malignancies, its safety profile requires further investigation to confirm these findings in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. Allouchery, M., Tomowiak, C., Lombard, T., et al.[2021]

In a phase 2 study involving 96 patients with high-risk locally advanced squamous cell carcinoma of the head and neck, Debio 1143 combined with standard chemoradiotherapy showed significantly better locoregional control at 18 months (54% vs. 33% for placebo), indicating its potential to enhance treatment efficacy.

Despite a high incidence of grade 3 or worse adverse events in both groups (85% in Debio 1143 vs. 87% in placebo), no deaths due to adverse events occurred in the Debio 1143 group, suggesting a safety profile that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study. Sun, XS., Tao, Y., Le Tourneau, C., et al.[2020]

The study found that combining dual PI3K and MEK inhibitors with agents like ABT-263 and entinostat significantly increased the effectiveness of cancer treatment by enhancing cytotoxicity and inducing apoptosis in solid cancer cell lines.

Bcl-xl and Mcl-1 were identified as key proteins that help cancer cells avoid apoptosis, suggesting that targeting these anti-apoptotic factors could improve the response to PI3K and MEK inhibitors in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage. Jokinen, E., Koivunen, JP.[2019]

In a phase 2 trial involving 124 women with untreated triple-negative breast cancer, the addition of the AKT inhibitor ipatasertib to paclitaxel significantly improved median progression-free survival to 6.2 months compared to 4.9 months with placebo, indicating its potential efficacy in this patient population.

Ipatasertib was associated with some adverse events, notably diarrhea in 23% of patients, but no severe treatment-related complications or deaths were reported, suggesting a manageable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Kim, SB., Dent, R., Im, SA., et al.[2022]

A study analyzing post-marketing data from the FDA Adverse Event Reporting System identified 10 cardiovascular events associated with ibrutinib, including supraventricular tachyarrhythmias and cardiomyopathy, highlighting significant safety concerns.

This research revealed disorders of sinus node function as a potential new adverse effect of ibrutinib, emphasizing the need for careful monitoring of cardiovascular health in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Toxicities of Ibrutinib: A Pharmacovigilance Study Based on the United States Food and Drug Administration Adverse Event Reporting System Database. Zheng, Y., Guo, X., Chen, C., et al.[2023]

Bruton's tyrosine kinase inhibitors (BTKis) are effective in treating B-cell malignancies but are associated with cardiovascular side effects, particularly an increased risk of atrial fibrillation, bleeding, and hypertension.

Newer generations of BTKis may have a lower risk of cardiovascular issues, but long-term safety data is still lacking, highlighting the need for careful management of cardiovascular risk factors in patients undergoing BTKi treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and Management of Cardiovascular Effects of Bruton's Tyrosine Kinase Inhibitors. Aghel, N., Baro Vila, RC., Lui, M., et al.[2023]

The recommended phase II dose (RP2D) of Debio 1143 is 200 mg/day, which was found to be safe and manageable when combined with high-dose cisplatin chemoradiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck.

The addition of Debio 1143 resulted in an overall response rate of 85% and a progression-free survival rate of 74% at 24 months, indicating promising preliminary efficacy for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Debio 1143, an Antagonist of Inhibitor of Apoptosis Proteins, Combined with Cisplatin Chemoradiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck. Le Tourneau, C., Tao, Y., Gomez-Roca, C., et al.[2021]

Immunotherapy targeting PD-1/PD-L1 and CTLA-4 has shown increased survival benefits in treating metastatic non-small cell lung cancer (NSCLC), but it is also associated with significant cardiotoxicity, particularly high-grade conduction disorders like 3rd degree heart block.

A case study highlighted a patient who developed 3rd degree heart block 16 days after starting combination therapy with ipilimumab and nivolumab, emphasizing that over 75% of immunotherapy-related cardiotoxicity cases occur within the first 6 weeks, which underscores the need for early identification and monitoring of high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy-associated complete heart block in a patient with NSCLC: A case report and literature review. Vartanov, A., Kalotra, A., Varughese, J., et al.[2021]

Citations

1. nature.com nature.com/articles/s41591-025-03783-8

CLDN18.2–targeting antibody–drug conjugate IBI343 in ... The median PFS was 6.8 months (95% CI = 2.8–7.5); the median OS was not reached, with events occurring in 36.8% participants. Efficacy of IBI343 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3037

Safety and efficacy of IBI343 (anti-claudin18.2 antibody- ... 2 (CLDN18.2) has emerged as a potential target for anti-cancer treatment. Herein, we report preliminary safety and efficacy results of IBI343, ...

3. prnewswire.com prnewswire.com/news-releases/asco-2025-oral-presentation-innovent-biologics-announces-updated-data-of-ibi343-novel-anti-cldn18-2-adc-from-the-phase-1-clinical-study-in-patients-with-advanced-pancreatic-cancer-302470512.html

Innovent Biologics Announces Updated Data of IBI343 ... IBI343 is the first ADC candidate to show encouraging efficacy and a favorable safety profile in the treatment of advanced pancreatic cancer.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40670773/

CLDN18.2-targeting antibody-drug conjugate IBI343 in ... IBI343 was well tolerated, with a manageable safety profile and promising efficacy in G/GEJ adenocarcinoma. Further research is required to ...

5. onclive.com onclive.com/view/ibi343-is-safe-generates-preliminary-efficacy-in-cldn18-2-advanced-gastric-gej-adenocarcinoma

IBI343 Is Safe, Generates Preliminary Efficacy in CLDN18. ... IBI343 was well tolerated and demonstrated signs of efficacy in patients with CLDN18.2-positive advanced gastric/GEJ adenocarcinoma.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06770439

NCT06770439 | IBI343 Combined With Chemotherapy in ... This study is a phase II study to evaluate the safety, tolerability and efficacy of IBI343 combined with chemotherapy in patients with advanced pancreatic ...