IBI363 for Advanced Solid Cancers

Recruiting at 9 trial locations

Overseen By William Liu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Must not be taking: Chemotherapy, Monoclonal antibodies

Disqualifiers: Inadequate organ function, Major surgery, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

178 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IBI363 (a PD-1/IL-2α bispecific antibody fusion protein) for individuals with advanced solid cancers unresponsive to other treatments. The main goals are to evaluate the drug's effectiveness, safety, and patient tolerance. IBI363 is administered through an IV every 2 or 3 weeks. Suitable candidates have advanced cancer that no longer responds to standard treatments and a life expectancy of at least 3 months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain cancer treatments recently, like chemotherapy within 2 weeks or certain antibodies within 4 weeks before starting the study drug.

Is there any evidence suggesting that IBI363 is likely to be safe for humans?

Research shows that IBI363 has undergone testing in people before. In earlier studies, patients with advanced cancers such as non-small cell lung cancer and melanoma tolerated it well. These trials found no new safety issues, suggesting the treatment is generally safe. However, every treatment can have side effects, and responses can vary. Ongoing research aims to ensure the treatment's safety and effectiveness for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced solid cancers, which often involve chemotherapy or targeted therapies, IBI363 is unique because it is administered as an intravenous infusion, potentially allowing for more controlled delivery. Researchers are excited about IBI363 because it represents a new approach to targeting cancer cells, possibly with fewer side effects compared to traditional chemotherapy. This innovative method could offer a more effective and patient-friendly option for those battling advanced solid tumors.

What evidence suggests that IBI363 might be an effective treatment for advanced solid cancers?

Research has shown that IBI363, the investigational treatment in this trial, holds promise for treating advanced solid tumors. Studies have found that this treatment works well over time, particularly for patients with non-small cell lung cancer (NSCLC) and melanoma. IBI363 is a bispecific antibody, targeting two proteins, PD-1 and IL-2α, that aid cancer growth. This approach enhances the immune system's ability to fight cancer cells more effectively. Early results indicate that even patients with hard-to-treat cancers, such as mucosal melanomas, benefit from this treatment. In early studies, patients have generally tolerated this treatment well. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors that haven't responded to other treatments. Specific details on who can join are not provided, but typically participants need to meet certain health standards and have a type of cancer the study targets.

Inclusion Criteria

Anticipated life expectancy of ≥ 3 months

Subjects have the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have had major surgery recently or will have one during the study.

I have had cancer treatment within the required time frame.

My bone marrow and organs are not functioning properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IBI363 as an intravenous infusion every 2 or 3 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IBI363

Trial Overview The trial is testing IBI363, which is being evaluated for its effectiveness and safety in treating advanced solid malignancies. It's an open-label, multicenter study, meaning both the researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: IBI363 Experimental Treatment 1 Intervention

IBI363 will be administered as an intravenous (IV) infusion every 2 weeks or every 3 weeks.

IBI363 is already approved in United States, China for the following indications:

Approved in United States as IBI363 for:

• Advanced melanoma (Fast Track Designation)

Approved in China as IBI363 for:

• Under clinical investigation for advanced solid malignancies

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

Published Research Related to This Trial

The engineered bispecific antibody targeting CD28H and PD-L1 enhances tumor-specific immune responses by stimulating T-cell and NK-cell activity, potentially leading to more effective cancer treatments.

This approach works by reducing inhibitory signaling from PD-L1 and boosting T-cell receptor signaling, which may result in long-lasting antitumor effects while minimizing adverse events associated with traditional checkpoint blockade therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation of T- and NK-cell Responses by a Bispecific Antibody Targeting CD28 Homolog and PD-L1. Ramaswamy, M., Kim, T., Jones, DC., et al.[2022]

The bispecific antibody (BsAb) designed to target both c-MET and PD-1 effectively induces degradation of c-MET in cancer cells and inhibits their growth, migration, and survival, demonstrating its potential as a cancer treatment.

In animal studies, BsAb significantly reduced tumor growth and chronic inflammation, suggesting it could enhance T cell activation and improve immune response against solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel bispecific c-MET/PD-1 antibody with therapeutic potential in solid cancer. Sun, ZJ., Wu, Y., Hou, WH., et al.[2018]

A new bispecific molecule combining an anti-PD-1 antibody with a multimeric GITR ligand enhances T cell activation and memory differentiation, potentially improving cancer immunotherapy outcomes.

In mouse models, this bispecific approach showed dose-dependent tumor growth inhibition, indicating that it effectively targets and activates GITR+PD-1+ T cells to combat tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-PD-1-GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy. Chan, S., Belmar, N., Ho, S., et al.[2022]

Bispecific antibodies, which target two different antigens on separate cells, have shown promise in recruiting immune cells to attack tumors, but previous studies faced challenges like low efficacy and side effects.

Recent advancements in antibody engineering and a better understanding of immune cell biology have led to the development of new bispecific antibodies, with the first of these now undergoing clinical trials for treating B-cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant bispecific antibodies for cellular cancer immunotherapy. Müller, D., Kontermann, RE.[2007]

IBI323, a bispecific antibody targeting both PD-L1 and LAG-3, shows promising anti-tumor effects in preclinical models, demonstrating superior immune stimulation and anti-tumor activity compared to its parent antibodies.

In humanized mouse models, IBI323 not only effectively blocked key immune checkpoints but also enhanced the activation of tumor-specific T cells, suggesting it could be a valuable new approach for overcoming resistance to existing PD-1/PD-L1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity. Jiang, H., Ni, H., Zhang, P., et al.[2021]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

Bispecific antibodies, like Removab and Blincyto, have shown significant potential in immuno-oncology, leading to increased interest and investment from pharmaceutical companies.

Currently, over 30 bispecific molecules are in clinical trials, highlighting their growing role as immune effector cell engagers in cancer treatment, with promising strategies targeting various immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? Del Bano, J., Chames, P., Baty, D., et al.[2020]

The bispecific antibody IBI315, which targets both PD-1 and Her2, shows enhanced antitumor effects in Her2-positive gastric cancer by improving the interaction between tumor cells and T cells, as demonstrated in both in vitro and in vivo models.

IBI315 induces pyroptosis in tumor cells through gasdermin B, leading to T cell activation and a positive feedback loop that enhances immune response, making it a promising immunotherapy for patients with Her2-positive gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1/Her2 Bispecific Antibody IBI315 Enhances the Treatment Effect of Her2-Positive Gastric Cancer through Gasdermin B-Cleavage Induced Pyroptosis. Lin, W., Zhang, Y., Yang, Y., et al.[2023]

Bispecific antibodies targeting the EGF-receptor and immune effector cell receptors significantly enhance tumor cell killing compared to conventional monoclonal antibodies, indicating improved efficacy in treating renal cell carcinoma.

Using whole blood from patients treated with myeloid growth factors like G-CSF or GM-CSF, the bispecific antibodies showed the highest cytotoxicity, with granulocytes identified as the most effective immune cells in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma. Elsässer, D., Stadick, H., Stark, S., et al.[2018]

A novel bispecific antibody, BiAb-1, effectively targets both PD-L1 and TIGIT, showing enhanced binding and cytokine production, which may improve immune responses against tumors.

BiAb-1 demonstrated superior anti-tumor efficacy compared to traditional PD-1/PD-L1 inhibitors in multiple tumor models, suggesting it could be a promising new treatment option for cancer patients resistant to current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of a novel anti PD-L1 X TIGIT bispecific antibody for the treatment of solid tumors. Xiao, Y., Chen, P., Luo, C., et al.[2022]

FS118, a bispecific antibody targeting LAG-3 and PD-L1, was well tolerated in a phase 1 study with 43 patients who had advanced cancer resistant to anti-PD-(L)1 therapy, showing no serious adverse events or dose-limiting toxicities.

The study demonstrated a disease control rate of 46.5%, with a higher rate of 54.8% in patients receiving doses of 1 mg/kg or greater, indicating potential efficacy in this difficult-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. Yap, TA., LoRusso, PM., Wong, DJ., et al.[2023]

TSAxCD28 bispecific antibodies can enhance the effectiveness of anti-PD-1 therapy, enabling immune responses and long-term memory against tumors that typically do not respond to PD-1 blockers, as demonstrated in preclinical models.

These bispecifics show minimal toxicity compared to other T cell activators, making them a promising and safe addition to cancer immunotherapy regimens, potentially improving outcomes for patients with resistant tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. Waite, JC., Wang, B., Haber, L., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8509

First-in-class PD-1/IL-2 bispecific antibody IBI363 in ... Here, we report safety and efficacy results from a phase I, multicenter, first-in-human study (NCT05460767) of IBI363 in pts with advanced NSCLC ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT463030

First-in-class PD-1/IL-2 bispecific antibody fusion protein ... More updated data on safety and efficacy will be presented at the meeting. Conclusions: IBI363 showed promising and durable efficacy in pts with various solid ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2502

Efficacy and safety results of a first-in-class PD-1/IL-2α-bias ... Pts with acral and mucosal melanomas show limited benefit from current therapies. IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody ...

4. takeda.com takeda.com/newsroom/newsreleases/2025/innovent/

Takeda Announces Oncology Partnership with Innovent IBI363 has demonstrated encouraging activity preclinically and in early clinical data in solid tumors, including non-small cell lung cancer and ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)00679-3/fulltext

VP4-2024: First-in-class PD-1/IL-2 bispecific antibody ... Conclusions. IBI363 was well tolerated in all pts with encouraging efficacy in advanced NSCLC and melanoma. Clinical trial identification.

6. prnewswire.com prnewswire.com/news-releases/innovent-delivers-oral-presentation-on-phase-1-clinical-data-of-ibi363-first-in-class-pd-1il-2-bias-bispecific-antibody-fusion-protein-in-advanced-non-small-cell-lung-cancer-at-the-2024-wclc-302243870.html

Innovent Delivers Oral Presentation on Phase 1 Clinical ... IBI363 is a first-in-class PD-1/IL-2 α-bias bispecific antibody fusion protein developed independently by Innovent Biologics.