AI-081 Antibody for Advanced Cancer

(BiPAVE-001 Trial)

Recruiting at 18 trial locations

Overseen By Kazu Kai, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: OncoC4, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Brain metastases, Cardiovascular diseases, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: 2

204 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

BIPAVE-001 is a Phase 1-2 study for evaluating the safety, pharmacokinetics (PK), and efficacy of AI-081 in solid tumors.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does allow for certain supportive treatments like thyroxine, insulin, and steroid replacement. There is a 28-day washout period for treatments with monoclonal antibodies.

How does the AI-081 antibody treatment differ from other cancer treatments?

The AI-081 antibody treatment is unique because it likely involves a novel mechanism of action or target, similar to other antibodies that target specific proteins overexpressed in cancer cells, such as integrins or growth factor receptors, which can lead to targeted cell death and reduced tumor growth. ^{1 2 3 4 5}

What data supports the effectiveness of the AI-081 drug for advanced cancer?

The research on similar treatments, like the monoclonal antibody mAb 2F8, shows that targeting the epidermal growth factor receptor (EGF-R) can block cancer cell growth and engage the immune system to attack cancer cells. This suggests that AI-081, if it works similarly, might also be effective in treating advanced cancer by using these mechanisms. ^{4 5 6 7 8}

Who Is on the Research Team?

Kai He, MD, PhD

Principal Investigator

The Ohio State University James Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who can use birth control and have good organ function. They must be able to perform daily activities with minimal assistance (ECOG ≤1) and have measurable disease by RECIST 1.1 standards.

Inclusion Criteria

I can carry out all my self-care but cannot do heavy physical work.

Measurable disease as determined by RECIST 1.1

Patient has voluntarily agreed to participate by giving written informed consent

Exclusion Criteria

Patients who are pregnant, breastfeeding, planning pregnancy, or fathering a child during the study or within 6 months after the last dosing of study drug

I haven't had major heart issues, infections, or certain illnesses in the last 6 months.

Patients with conditions that might confound the study results or interfere with participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

First-in-human dose escalation study to determine the recommended Phase 2 dose (RP2D) of AI-081 monotherapy

3 weeks

1 visit every 3 weeks

Dose Optimization

Dose optimization trials comparing the safety and clinical activities of AI-081 at RP2D and RP2D-1, either as monotherapy or in combination with standard of care

9 weeks

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AI-081

Trial Overview AI-081, a bispecific antibody targeting PD-1 and VEGF, is being tested in two parts: Part A to find the safest dose, and Part B to compare that dose's safety and effectiveness alone or with standard treatments.

How Is the Trial Designed?

Group I: AI-081 Experimental Treatment 1 Intervention

AI-081 will be given by IV infusion in designated dose, q3w.

Who Is Running the Clinical Trial?

OncoC4, Inc.

Lead Sponsor

Trials

8

Recruited

1,800+

Published Research Related to This Trial

The monoclonal antibody 2F8 effectively blocks EGF-R signaling and inhibits the growth of EGF-R-overexpressing cancer cells, demonstrating its potential as a targeted therapy for tumors with high EGF-R levels.

2F8 also induces antibody-dependent cell-mediated cytotoxicity (ADCC) at low concentrations, suggesting that it can effectively combat tumors even with lower doses, highlighting its dual mechanism of action in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual mode of action of a human anti-epidermal growth factor receptor monoclonal antibody for cancer therapy. Bleeker, WK., Lammerts van Bueren, JJ., van Ojik, HH., et al.[2019]

PF-04605412 (PF-5412) is a fully human IgG1 monoclonal antibody that effectively neutralizes integrin α5β1, showing strong antitumor efficacy in animal studies, particularly in tumors with high α5 expression.

The antibody enhances antibody-dependent cellular cytotoxicity (ADCC) by engaging natural killer (NK) cells and macrophages, and its combination with sunitinib significantly boosts antitumor effects, indicating its potential for treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual functional monoclonal antibody PF-04605412 targets integrin alpha5beta1 and elicits potent antibody-dependent cellular cytotoxicity. Li, G., Zhang, L., Chen, E., et al.[2018]

The chimeric antibody mAb 806 (ch806) specifically targets tumor cells with overexpressed or mutant forms of the epidermal growth factor receptor (EGFR), showing excellent tumor site targeting in patients without affecting normal tissues.

In clinical studies, ch806 demonstrated no significant toxicity, highlighting its potential as a safe and effective treatment option for various cancers compared to other EGFR-targeting antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors. Scott, AM., Lee, FT., Tebbutt, N., et al.[2022]

The study developed a one-time application of a genetically engineered immune checkpoint inhibitor (ICI) using a recombinant adeno-associated vector (rAAV) that targets PD-L1, showing significant protection against tumor growth in mouse models of colorectal and breast cancer.

This approach led to enhanced CD8+ T-cell function and a favorable shift in the tumor microenvironment, indicating that rAAV-PD-L1-scFv could be a safer and more effective alternative to traditional monoclonal antibodies in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Checkpoint Blockade by PD-L1 Single-Chain Antibody Confers Potent Antitumor Immunity and Long-term Survival. Wang, H., Khattar, V., Hensel, JA., et al.[2023]

The human IgG1 antibody adecatumumab shows significantly lower anti-tumor activity in mouse models due to reduced binding affinity to murine Fc-gamma receptors, highlighting the importance of species compatibility in antibody therapies.

By genetically fusing the variable domains of adecatumumab to a murine IgG2a backbone, the resulting mu-adecatumumab demonstrated much higher anti-tumor efficacy in preventing lung metastases in mice, suggesting that using species-appropriate antibody formats can enhance therapeutic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exchanging human Fcgamma1 with murine Fcgamma2a highly potentiates anti-tumor activity of anti-EpCAM antibody adecatumumab in a syngeneic mouse lung metastasis model. Lutterbuese, P., Brischwein, K., Hofmeister, R., et al.[2019]

The monoclonal antibody PR81, which targets the MUC1 protein overexpressed in breast tumors, demonstrated high immunoreactivity and significant tumor growth inhibition (up to 80%) in vitro against the MCF7 breast cancer cell line.

In vivo studies in BALB/c mice showed that the radiolabeled PR81 had a favorable biodistribution profile with no significant accumulation in vital organs, and it effectively visualized tumors with high sensitivity, indicating its potential as a promising radioimmunotherapeutic agent for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new radiopharmaceutical compound (131I-PR81) for radioimmunotherapy of breast cancer: labeling of antibody and its quality control. Mohammadnejad, J., Rasaee, MJ., Babaei, MH., et al.[2019]

The hybridoma clone C3A8 produces a specific IgM monoclonal antibody that strongly binds to MCF7 breast cancer and HT29 colon cancer cells, while showing minimal reactivity with HeLa cells, indicating its potential for targeted cancer research.

MAb C3A8 can detect a specific 55 kDa protein in cancer cell extracts and has shown positive reactions in human breast and colon cancer tissues, but not in normal tissues, suggesting its utility in distinguishing cancerous from healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mouse IgM monoclonal antibody recognizes breast and colon cancer. Bakar, AF., Alitheen, NB., Keong, YS., et al.[2009]

The cT84.66 minibody, an engineered antibody construct, successfully targeted tumors in 7 out of 8 patients with colorectal cancer who had not received prior treatment, indicating its potential as an effective imaging agent.

The minibody demonstrated a mean serum residence time of 29.8 hours with no drug-related adverse reactions, suggesting it is well tolerated and has favorable pharmacokinetics compared to traditional antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot trial evaluating an 123I-labeled 80-kilodalton engineered anticarcinoembryonic antigen antibody fragment (cT84.66 minibody) in patients with colorectal cancer. Wong, JY., Chu, DZ., Williams, LE., et al.[2007]

Citations

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

Dual mode of action of a human anti-epidermal growth factor receptor monoclonal antibody for cancer therapy. [2019]

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

Dual functional monoclonal antibody PF-04605412 targets integrin alpha5beta1 and elicits potent antibody-dependent cellular cytotoxicity. [2018]

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

A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors. [2022]

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

Systemic Checkpoint Blockade by PD-L1 Single-Chain Antibody Confers Potent Antitumor Immunity and Long-term Survival. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Exchanging human Fcgamma1 with murine Fcgamma2a highly potentiates anti-tumor activity of anti-EpCAM antibody adecatumumab in a syngeneic mouse lung metastasis model. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A new radiopharmaceutical compound (131I-PR81) for radioimmunotherapy of breast cancer: labeling of antibody and its quality control. [2019]

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

A mouse IgM monoclonal antibody recognizes breast and colon cancer. [2009]

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

Pilot trial evaluating an 123I-labeled 80-kilodalton engineered anticarcinoembryonic antigen antibody fragment (cT84.66 minibody) in patients with colorectal cancer. [2007]