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

Trial Summary

What is the purpose of this trial?

This is a Phase 2, open-label, multicenter study designed to evaluate the efficacy, safety and tolerability of IBI363 (study drug) in subjects with advanced, refractory solid malignancies.

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.

What data supports the effectiveness of the drug IBI363 for advanced solid cancers?

Research on similar bispecific antibodies, like those targeting PD-1 and other immune checkpoints, shows they can enhance the body's immune response against tumors. These antibodies have been effective in preclinical models by activating immune cells to attack cancer cells, suggesting potential for IBI363 in treating solid cancers. ^{1 2 3 4 5}

What safety data exists for IBI363 or similar bispecific antibodies in humans?

There is no specific safety data available for IBI363, but similar bispecific antibodies like MEDI5752 have been reported to be well tolerated in early trials, suggesting a potential for safety in humans. ^{2 6 7 8 9}

What makes the drug IBI363 unique for treating advanced solid cancers?

IBI363 is unique because it is a bispecific antibody fusion protein that targets both PD-1, a protein that helps cancer cells evade the immune system, and IL-2α, which can enhance immune cell activity, potentially offering a more targeted and effective approach to treating advanced solid cancers compared to traditional therapies. ^{1 2 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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 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]

References

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

A novel bispecific c-MET/PD-1 antibody with therapeutic potential in solid cancer. [2018]

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

PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity. [2021]

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

Immunomodulation of T- and NK-cell Responses by a Bispecific Antibody Targeting CD28 Homolog and PD-L1. [2022]

4. United States 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. [2023]

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

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. [2021]

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? [2020]

8. England pubmed.ncbi.nlm.nih.gov

Discovery of a novel anti PD-L1 X TIGIT bispecific antibody for the treatment of solid tumors. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Recombinant bispecific antibodies for cellular cancer immunotherapy. [2007]

10. Germany 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

An anti-PD-1-GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy. [2022]

12. Greece pubmed.ncbi.nlm.nih.gov

Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma. [2018]