AI-081 Antibody for Advanced Cancer

(BiPAVE-001 Trial)

Recruiting at 19 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?

This trial tests a new treatment called AI-081, an antibody therapy for individuals with advanced solid tumors, to assess its safety and effectiveness. Participants receive the treatment through an IV infusion every three weeks. Those diagnosed with advanced or spreading solid tumors who can engage in daily activities might be suitable candidates. The trial aims to learn more about AI-081's effects on the body and its efficacy against cancer. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in humans.

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.

Is there any evidence suggesting that AI-081 is likely to be safe for humans?

Research has shown that AI-081 is very safe in early testing. Studies found that even at the smallest dose tested (1 mg/kg), AI-081 was well-tolerated, with most patients experiencing no serious side effects. This treatment is a bispecific antibody, targeting two proteins in the body, PD-1 and VEGF, which are involved in cancer growth.

The current trials are in Phase 1-2, indicating they are still in the early stages of testing to assess the treatment's safety and mechanism in the body. Although more testing is needed to fully understand its safety, early results are promising for people with advanced cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AI-081 because it represents a novel approach to treating advanced cancer. Unlike traditional cancer treatments that often rely on chemotherapy or radiation to kill cancer cells, AI-081 is an antibody designed to specifically target and bind to cancer cells, potentially sparing healthy cells and reducing side effects. This targeted mechanism of action could offer a more precise and effective treatment option. Additionally, AI-081 is administered via IV infusion every three weeks, which might offer a more convenient dosing schedule compared to some existing therapies.

What evidence suggests that AI-081 might be an effective treatment for advanced cancer?

Research has shown that AI-081, a new treatment under study in this trial, could aid in managing advanced solid tumors. It targets two key cancer areas: PD-1 and VEGF, which assist tumors in growing and evading the immune system. Early studies found that AI-081 blocks these areas more effectively than similar treatments. Even at low doses, patients responded well, indicating the treatment's effectiveness. This makes AI-081 a promising option for treating challenging cancers. ^{1 2 3 4 6}

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

My organ functions are within normal ranges according to recent tests.

Exclusion Criteria

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

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.

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 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 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]

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 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 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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06635785

Safety, Pharmacokinetics, and Efficacy of AI-081, a ...

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

2.

oncoc4.com

oncoc4.com/press-releases/oncoc4-doses-first-patient-with-potential-best-in-class-pd-1-vegf-bispecific-antibody-ai-081-in-phase-2-portion-of-bipave-001-trial-for-advanced-solid-tumors-in-us/

OncoC4 Doses First Patient with Potential Best-in-Class ...

Excellent safety observed across initial dose escalation with objective response at the lowest dose tested (1 mg/kg of AI-081).

3.

withpower.com

withpower.com/trial/phase-2-neoplasms-11-2024-5cc82

AI-081 Antibody for Advanced Cancer (BiPAVE-001 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 ...

4.

curetoday.com

curetoday.com/view/new-trials-advance-treatments-for-lymphoma-lung-cancer-and-sarcomas

New Trials Advance Treatments for Lymphoma, Lung ...

Preclinical studies showed AI-081 binds both targets strongly and works better than similar drugs by enhancing PD-1 blockade while blocking VEGF ...

5.

clin.larvol.com

clin.larvol.com/trial-detail/NCT06635785

Safety, Pharmacokinetics, and Efficacy of AI-081, a ...

Safety, pharmacokinetics, and efficacy of AI-081, a bispecific antibody for PD-1 and VEGF in advanced solid tumors.

6.

synapse.patsnap.com

synapse.patsnap.com/article/fda-clears-oncoc4s-ind-for-pd-1vegf-bispecific-ai-081-in-advanced-tumors

FDA Clears OncoC4's IND for PD-1/VEGF Bispecific AI-081 ...

This study focuses on the safety, pharmacokinetics, and efficacy of AI-081 monotherapy in patients with advanced solid tumors. AI-081 ...