IBI343 for Cancer

Recruiting in Palo Alto (17 mi)

+38 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Must not be taking: CYP3A4 inhibitors, Live vaccines

Disqualifiers: Infections, CNS metastases, Hypertension, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This is a Phase 1a/b, multicenter, open-label, first-in-human, dose escalation, expansion and extension study to evaluate the safety, tolerability, and DLTs to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and preliminary efficacy of IBI343 (study drug) in participants with locally advanced unresectable or metastatic solid tumors.

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.

What safety data exists for IBI343 in humans?

The safety data for Ibrutinib, which may be related to IBI343, shows that it can cause cardiovascular issues like heart rhythm problems and heart failure. These findings are based on large-scale safety databases and highlight the importance of monitoring for heart-related side effects. ^{1 2 3 4 5}

What makes the drug IBI343 unique for cancer treatment?

IBI343 may target specific mutations in the PIK3CA gene, which are associated with cancer progression and poor prognosis, potentially offering a novel approach compared to existing treatments that do not specifically address these genetic mutations. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

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 am 18 years old or older.

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

Trial Timeline

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

Treatment Details

Interventions

• IBI343 (Monoclonal Antibodies)

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.

Participant Groups

Group I: Phase 1b Experimental Treatment 1 Intervention

Phase 1b Dose Extension: IBI343 will be administered at RP2D.

Group II: Phase 1a Experimental Treatment 1 Intervention

Phase 1a Dose Escalation: IBI343 will be administered intravenously (IV) at different dose levels following accelerated titration for the first 2 dose levels and traditional 3+3 dose escalation design for following levels. Phase 1a 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=30-40). Dose levels 4.5mg/kg and 6mg/kg will be studied. Phase 1a Dose Expansion: IBI343 will be administered at dose levels which is equal or lower than MTD. Each dose level contains no more than 60 subjects (including subjects in dose escalation).

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+

TigerMed

Industry Sponsor

Trials

4

Recruited

1,100+

Findings from Research

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]

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]

References

1. France 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. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. [2021]

3. Switzerland 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Diagnosis and Management of Cardiovascular Effects of Bruton's Tyrosine Kinase Inhibitors. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Immunotherapy-associated complete heart block in a patient with NSCLC: A case report and literature review. [2021]

6. United States 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. [2022]

7. England 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. [2020]

8. United States 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. [2021]

9. Greece pubmed.ncbi.nlm.nih.gov

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

10. England 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. [2022]