HB0045 Injection for Advanced Solid Cancers

Recruiting at 2 trial locations

Overseen By Nashat Gabrail, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shanghai Huaota Biopharmaceutical Co., Ltd.

Must not be taking: Corticosteroids, Immunosuppressants, Antibiotics, others

Disqualifiers: CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 6

71 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of HB0045, an injection designed to treat advanced solid cancers. The study aims to determine patient tolerance and assess whether the treatment can shrink or control tumors. Researchers seek participants with advanced solid tumors, such as pancreatic, colorectal, or ovarian cancer, who have not responded to standard treatments. Individuals with these cancers and no remaining treatment options may qualify. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain treatments like anticancer therapy or major surgery within a specific time frame before starting the trial. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that HB0045 Injection is likely to be safe for humans?

Research has shown that HB0045, a new cancer drug, targets a protein called CD73 found on cancer cells. Studies have found that HB0045 attaches to two parts of this protein, potentially slowing tumor growth. Although specific safety details from these studies aren't provided, the drug is currently in early trials. Researchers are primarily assessing its safety and tolerability.

In these early trials, participants receive close monitoring to detect any side effects or adverse reactions. While HB0045 isn't approved for any use yet, its testing indicates some confidence in its potential safety. Participants will be carefully observed for any signs of harm or other side effects to ensure maximum safety. ^{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, HB0045 Injection is unique because it utilizes a novel mechanism of action. This innovative treatment is administered intravenously every three weeks, potentially offering a more manageable dosing schedule compared to daily oral therapies. Researchers are particularly excited about HB0045 because it targets cancer cells in a way that could potentially reduce side effects and improve effectiveness, offering new hope for patients with these challenging conditions.

What evidence suggests that HB0045 Injection might be an effective treatment for advanced solid cancers?

Research has shown that HB0045 Injection could be a promising treatment for advanced solid cancers. HB0045 targets CD73, a protein that helps cancer cells evade the immune system. Early lab studies demonstrated that HB0045 can slow tumor growth. Initial human trials suggested that HB0045 might shrink tumors in some patients, particularly those with no other treatment options. Although more research is needed, these early results offer hope for its effectiveness in treating advanced cancers. ^{1 3 6 7 8}

Who Is on the Research Team?

Yongmin Yang

Principal Investigator

Shanghai Huaota Biopharmaceutical Co., Ltd.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors who've tried all standard treatments without success are eligible for this trial. They must understand the study, be willing to follow procedures, and have a life expectancy of at least 12 weeks. Key requirements include proper organ function, no recent severe bowel issues or surgeries, and controlled prior treatment side effects (except hair loss and mild neuropathy). Specific cancer types like pancreatic, colorectal, ovarian among others are included.

Inclusion Criteria

Coagulation function i. International normalized ratio (INR) or prothrombin time (PT)≤ 1.5×ULN (unless the patient is on stable dose of oral anticoagulant) ii. Activated partial thromboplastin time (APTT)≤ 1.5×ULN

I have not had any surgery to create an opening in my intestine in the last 3 months.

I have a tumor that can be measured by scans.

Exclusion Criteria

I haven't had cancer, except for specific types, in the last 5 years.

I have stable brain or spinal cord cancer and am on low-dose steroids or none.

I haven't had a stroke, heart attack, severe heart failure, or serious heart rhythm problems in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive HB0045 as a monotherapy at escalating doses to evaluate safety and tolerability

Up to 3 months

Every 3 weeks (in-person)

Phase II Treatment

Evaluation of safety and preliminary efficacy of HB0045 at the RP2D in specific cancer cohorts

Up to 24 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• HB0045 Injection

Trial Overview The HB0045 drug is being tested in patients with various advanced solid tumors to assess its safety, tolerability, how it affects the body (pharmacokinetics/pharmacodynamics), immune response it triggers (immunogenicity), potential biomarkers for effectiveness and its ability to fight cancer.

How Is the Trial Designed?

Group I: HB0045 Experimental Treatment 1 Intervention

HB0045 IV every 3 weeks (q3w)

Who Is Running the Clinical Trial?

Shanghai Huaota Biopharmaceutical Co., Ltd.

Lead Sponsor

Trials

12

Recruited

810+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Gabrail Cancer Center Research

Collaborator

Trials

3

Recruited

160+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

CD73 is significantly overexpressed in colorectal cancer (CRC) tissues compared to normal tissues, with high expression found in approximately 44.8% to 50.4% of patients in two independent cohorts.

High levels of CD73 are associated with poorer overall survival rates and serve as an independent prognostic biomarker for CRC, indicating its potential role in predicting patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. Wu, XR., He, XS., Chen, YF., et al.[2022]

The monoclonal antibody (124)I huA33 effectively targets colorectal cancer, showing good localization in tumors with a median uptake significantly higher than in normal colon tissue, indicating its potential for cancer imaging and treatment.

The study found no significant toxicity associated with (124)I huA33, and the pharmacokinetics were consistent across different administration routes, confirming its safety and efficacy in patients with colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(124)I-huA33 antibody PET of colorectal cancer. Carrasquillo, JA., Pandit-Taskar, N., O'Donoghue, JA., et al.[2021]

The (177)Lu-labeled huA33 monoclonal antibody specifically targets colorectal cancer cells, showing a high tumor uptake of 134% ID/g at 72 hours post-injection, indicating its potential effectiveness in treating colorectal carcinoma.

The biodistribution study demonstrated low uptake in normal tissues and a high tumor-to-blood ratio (70) after 10 days, suggesting that (177)Lu-huA33 is stable and could be a promising candidate for radioimmunotherapy with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterization of 177Lu-huA33: a radioimmunoconjugate against colorectal cancer. Almqvist, Y., Steffen, AC., Tolmachev, V., et al.[2013]

Elevated CD73 expression is common in non-small cell lung cancer (NSCLC), particularly in tumors with RAS or RTK oncogenes, and is associated with immune tolerance and therapy resistance, indicating a potential target for new treatments.

The novel CD73-targeted antibody-drug conjugate (Hu001-MMAE) showed strong anti-tumor effects in mouse models of NSCLC, enhancing immune responses and effectively inhibiting tumor growth, suggesting it could be a promising therapy for advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Mechanisms of Novel CD73-Targeted Antibody and Antibody-Drug Conjugate in Inhibiting Lung Tumor Growth and Promoting Antitumor Immune-Effector Function. Jin, R., Liu, L., Xing, Y., et al.[2022]

CD73 is an important immune checkpoint that helps tumors grow by weakening the immune response and encouraging blood vessel formation, making it a key target for cancer treatment.

Combining CD73 inhibitors with other therapies, like immune checkpoint blockers, has shown enhanced antitumor effects in preclinical studies and promising results in patients with advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD73: an emerging checkpoint for cancer immunotherapy. Chen, S., Wainwright, DA., Wu, JD., et al.[2023]

The chimeric antibody B72.3-1-3 retains specific binding to LS174T tumor cells and shows similar biodistribution patterns to the native murine antibody B72.3, indicating it can effectively target tumors.

B72.3-1-3 significantly enhances the ability of human lymphocytes to kill LS174T tumor cells, suggesting that chimerization may improve therapeutic efficacy while potentially reducing immune responses against murine antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative biodistribution and antibody-dependent cellular cytotoxicity of native and heavy chain chimeric antibody. Gallinger, S., Papa, MZ., Reilly, RM., et al.[2016]

Targeting CD73 in cancer treatment can enhance the body's natural anti-tumor immune responses, potentially improving the effectiveness of cancer therapies.

Blocking CD73 may also reduce the ability of tumor cells to spread (metastasize), suggesting a dual benefit in both boosting immune response and limiting cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The double-edge sword effect of anti-CD73 cancer therapy. Stagg, J.[2021]

In a study of 198 breast cancer patients, CD73 was found to be expressed in 25.4% of all breast cancer cases, with a higher expression rate of 30.9% in invasive breast cancer, indicating its potential role in tumor progression.

CD73 expression was linked to more advanced disease characteristics, such as higher T-stage and node metastasis, but did not significantly affect disease-free survival or overall survival rates, suggesting it could serve as a prognostic marker and a target for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of CD73 is associated with tumor progression and intratumoral inflammation in breast cancer. Choi, HR., Oh, HK., Park, SH., et al.[2022]

In a phase I trial involving 15 patients with metastatic colorectal cancer, the maximum tolerated dose of the radioimmunotherapy 131I-huA33 was determined to be 40 mCi/m2, with effective tumor targeting observed in all patients.

While some hematologic toxicity was noted, including grade 4 neutropenia at higher doses, there were no acute infusion-related adverse events or gastrointestinal toxicity, suggesting a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of 131I-huA33 in patients with advanced colorectal carcinoma. Chong, G., Lee, FT., Hopkins, W., et al.[2014]

Monoclonal antibody B72.3 has been effectively used in clinical trials for identifying the TAG-72 antigen and localizing tumors in carcinoma patients, showing a 70% success rate in tumor localization from biopsy specimens.

The use of MAb B72.3 has significantly advanced the development of 'radioimmunoguided surgery', a new intraoperative technique that enhances the precision of tumor removal during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in the management of carcinoma patients. Roselli, M., Casciani, CU., Guadagni, F., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06056323

A Study of HB0045 Injection in Patients With Advanced ... In the phase II study, the safety and preliminary efficacy of HB0045 at the RP2D will be evaluated in cohorts of patients with pancreatic, colorectal, ovarian ...

2. withpower.com withpower.com/trial/phase-2-neoplasms-8-2023-1c4d5

HB0045 Injection for Advanced Solid Cancers This trial tests HB0045, a new cancer drug, on patients with advanced solid tumors who have no other treatment options.

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-cd73-monoclonal-antibody-hb0045

Clinical Trials Using Anti-CD73 Monoclonal Antibody ... Review the clinical trials studying anti-cd73 monoclonal antibody hb0045 on this list and use the filters to refine the results by age and location.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11685497/

An antibody cocktail targeting two different CD73 epitopes ... We evaluated tumor growth inhibition by comparing the efficacy of the HB0045 antibody cocktail to that of HB0038, HB0039, and Oleclumab. As ...

5. withpower.com withpower.com/trial/phase-2-neoplasms-7-2023-b147d

HB0045 Injection for Solid Tumors · Info for Participants The study aims to find the safest and most effective dose by giving the drug in gradually higher amounts and monitoring for side effects and tumor response.

6. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/anti-cd73-monoclonal-antibody-hb0045

Definition of anti-CD73 monoclonal antibody HB0045 Upon administration, anti-CD73 monoclonal antibody HB0045 targets and binds to two different epitopes of CD73 on tumor cells. HB0038 specifically binds to ...

7. nature.com nature.com/articles/s41467-024-55207-9

An antibody cocktail targeting two different CD73 epitopes ... These data suggest that HB0045-mediated internalization could efficiently decrease CD73 protein levels on the cell surface, particularly where ...

8. delta.larvol.com delta.larvol.com/Products/?ProductId=057da3a2-692d-4f71-9036-2f7673c1ab01

HB0045 / Zhejiang Huahai Pharma An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control. · A Study of HB0045 Injection in Patients With Advanced ...