ONC-841 for Cancer

Recruiting at 7 trial locations

Overseen By Imaan Khan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: OncoC4, Inc.

Must not be taking: Anticancer, Immune, Cytokine, others

Disqualifiers: Active brain metastases, Cardiovascular, Infections, others

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

Compensation: Varies

Number of Visits: 4

Duration: 84 days

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ONC-841 for individuals with advanced or spreading solid tumors. The primary goal is to determine a safe and effective dose by administering the treatment through an IV at varying levels. It suits those diagnosed with solid tumors that have spread or are at an advanced stage and are seeking new treatment options. Participants should manage daily activities with ease and have a measurable target tumor. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for cancer drugs: 5 half-lives or 21 days for chemotherapy, whichever is shorter, and 28 days for monoclonal antibody therapy. However, supportive care medications like thyroxine, insulin, and steroid replacement are allowed.

Is there any evidence suggesting that ONC-841 is likely to be safe for humans?

Research shows that ONC-841 is currently being tested in humans to assess its safety. This early research stage aims to determine the appropriate dose and identify any side effects. Since researchers are testing ONC-841 in people for the first time, its tolerability remains unknown. The main goal of such studies is to ensure the treatment's safety at various doses. If the treatment has few serious side effects and is well-tolerated, it may proceed to further testing. Detailed safety information for ONC-841 in humans is not yet available, but early studies like this are crucial for understanding the safety of new treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer, which often include chemotherapy and radiation, ONC-841 is unique because it is administered via IV infusion and operates on a potentially novel mechanism. Researchers are excited about this treatment because it could offer a more targeted approach, reducing damage to healthy cells and potentially minimizing side effects. Additionally, the infusion method allows for precise dosing, which may enhance the effectiveness and safety profile compared to some traditional treatments.

What evidence suggests that ONC-841 might be an effective treatment for cancer?

Research suggests that ONC-841, the investigational treatment in this trial, might help treat advanced solid tumors. It stops signals that usually prevent immune cells from attacking cancer cells. In early lab studies, ONC-841 enabled immune cells, such as macrophages and neutrophils, to "eat" cancer cells more effectively. These studies also showed that it improved the function of T cells, which are important for fighting tumors. Although limited information exists from human studies, these early results indicate that ONC-841 could help the immune system better find and destroy cancer cells. ^{1 2 4 6 7}

Who Is on the Research Team?

Tianhong Li

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who are relatively fit (ECOG score ≤ 1), weigh at least 40 kg, and have proper organ function. They must have a confirmed diagnosis with measurable disease and agree to use contraception. Participants will provide consent and may need to give tissue samples.

Inclusion Criteria

Must have measurable target lesion according to RECIST V1.1

Voluntary agreement to participate as evidenced by written informed consent

Agree to give archival or other diagnostic tissue recut slides or an optional new tumor biopsy

Exclusion Criteria

Patient with a different cancer other than the one treated under this protocol, which requires systemic treatments within 24 months prior to C1D1

Patients with known psychiatric or substance abuse disorders may interfere with cooperation with the requirements of the trial

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ONC-841 via IV infusion every 4 weeks, with dose escalation from 0.03 mg/kg to 30 mg/kg

84 days

Visits every 4 weeks for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ONC-841

Trial Overview The study tests different doses of ONC-841, an intravenous drug for treating advanced solid tumors. It's an early-phase trial (Phase I) that gradually increases the dose from 0.03 mg/kg to 30 mg/kg to find the safest and most effective level.

How Is the Trial Designed?

Group I: ONC-841 Experimental Treatment 1 Intervention

ONC-841 will be given by IV infusion in designated dose, q4w.

Who Is Running the Clinical Trial?

OncoC4, Inc.

Lead Sponsor

Trials

8

Recruited

1,800+

Published Research Related to This Trial

In a study of 30 pairs of gastric tissue samples from patients with gastric adenocarcinoma, SIX1 gene expression was found to be decreased in tumor samples overall, but significantly increased in diffuse-type gastric cancer, indicating a potential link between SIX1 expression and cancer type.

The research suggests that SIX1 gene expression could serve as a promising biomarker for predicting disease outcomes, particularly since higher expression levels were associated with more advanced tumor grades, especially between grade I and grade III, which correlates with poorer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SIX1 overexpression in diffuse-type and grade III gastric tumors: Features that are associated with poor prognosis. Emadi-Baygi, M., Nikpour, P., Emadi-Andani, E.[2022]

High levels of Six1 are linked to worse outcomes in luminal breast cancers, especially the luminal B subtype, and are enriched in tumor-initiating cell (TIC) populations, indicating its role in cancer progression.

Six1 promotes TIC characteristics by activating TGF-β and ERK signaling pathways, and using MEK1/2 inhibitors can effectively reduce tumor formation and metastasis in breast cancer cells with high Six1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways. Iwanaga, R., Wang, CA., Micalizzi, DS., et al.[2021]

The transcription factor Six1 is overexpressed in pancreatic ductal adenocarcinomas (PDAC) and its inhibition leads to decreased cancer cell motility and delayed tumor growth, suggesting its role in tumor progression.

Targeting Six1 may provide a new therapeutic strategy for pancreatic cancer, as its down-regulation resulted in significant changes in tumor characteristics and reduced the cancer stem cell phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Six1 affects tumour invasion and the expression of cancer stem cell markers in pancreatic cancer. Lerbs, T., Bisht, S., Schölch, S., et al.[2023]

The transcription factor SIX1 is found to be upregulated in human tumor tissues, and higher levels of SIX1 are associated with lower immune cell infiltration and poorer survival rates in cancer patients.

Deleting SIX1 in cancer cells leads to reduced tumor growth and improved antitumor immunity, suggesting that targeting SIX1 could enhance cancer immunotherapy by promoting immune cell activity in the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Homeoprotein SIX1 compromises antitumor immunity through TGF-β-mediated regulation of collagens. Liu, W., Gao, M., Li, L., et al.[2023]

In a review of 26 studies involving 3607 patients, the combination of PD-L1 inhibitors with CTLA-4 inhibitors resulted in a lower incidence of all-grade adverse events (67%) compared to the combination of PD-1 inhibitors with CTLA-4 inhibitors (89%).

This suggests that using PD-L1 inhibitors in combination therapy may offer a safer option with fewer treatment-related side effects than PD-1 inhibitors when paired with CTLA-4 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in clinical trials: a meta-analysis. Mi, Z., Zhang, Y., Feng, Z., et al.[2022]

Six1 is significantly upregulated in osteosarcoma cell lines compared to normal human osteoblastic cells, indicating its potential role in cancer development.

In osteosarcoma cells, Six1 promotes cell proliferation and migration while inhibiting apoptosis, suggesting it could be a key factor in tumor growth and a potential target for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Six1 promotes apoptosis, suppresses proliferation, and migration of osteosarcoma cells. Hua, L., Fan, L., Aichun, W., et al.[2021]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

A systematic review of 161 studies involving 17,197 patients revealed that combination therapies with PD-1 or PD-L1 inhibitors have high incidences of treatment-related adverse events, with chemotherapy combinations showing the highest overall incidence at 97.7%.

The most common all-grade adverse events across these therapies included anemia and fatigue, while grade 3 or higher adverse events were primarily neutropenia and hypertension, providing crucial safety information for clinicians managing cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis. Zhou, X., Yao, Z., Bai, H., et al.[2021]

In a network meta-analysis of six phase III clinical trials involving 4053 patients, PD-L1 inhibitor monotherapy was found to significantly reduce the risk of treatment-related adverse events (AEs) compared to platinum-based chemotherapy, with a risk ratio of 0.722 for any grade AEs and 0.406 for grade 3-5 AEs.

While PD-L1 inhibitors showed improved safety outcomes overall, they were associated with a higher risk of immune-related AEs compared to chemotherapy, indicating a need for careful monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis. García Campelo, MR., Arriola, E., Campos Balea, B., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06352359

Safety, Pharmacokinetics (PK), and Efficacy of ONC 841 in ... ONC-841 binds to Siglec10 to block the "do not eat me" signals that cancer cells give to immune system, which allow macrophages and neutrophils to "eat" the ...

2. oncoc4.com oncoc4.com/press-releases/oncoc4-announces-new-preclinical-data-highlighting-onc-841-a-novel-siglec-10-antibody-as-a-potential-new-class-of-therapeutics-for-alzheimers-disease/

SIGLEC 10 identified as a genetic driver for amyloid plaque ... The potential of ONC-841 to treat AD is supported by preclinical data from two mouse models showing normalization of microglia function and ...

3. nature.com nature.com/articles/s41591-024-03398-5

Prediction of checkpoint inhibitor immunotherapy efficacy ... In this study, we explored whether a machine learning system could predict ICI outcomes using routine blood tests and standard clinical variables.

4. synapse.patsnap.com synapse.patsnap.com/article/oncoc4-doses-first-patient-in-phase-1-trial-for-siglec10-inhibitor-onc-841-for-solid-tumors

OncoC4 Doses First Patient in Phase 1 Trial for SIGLEC10 ... In preclinical studies, ONC-841 increased phagocytosis of cancer cells and improved the function of tumor-infiltrating T cells and innate cells.

5. withpower.com withpower.com/trial/phase-1-solid-tumors-advanced-solid-tumors-5-2024-13e8c

ONC-841 for Cancer · Recruiting Participants for Phase ... This Phase 1 medical study run by OncoC4, Inc. is evaluating whether ONC-841 will have tolerable side effects & efficacy for patients with Solid Tumors.

6. synapse.patsnap.com synapse.patsnap.com/blog/oncoc4-initiates-phase-1-trial-of-siglec10-inhibitor-onc-841-for-solid-tumors

OncoC4 Initiates Phase 1 Trial of SIGLEC10 Inhibitor ONC- ... Preliminary data on the safety, pharmacokinetics, and clinical activity of ONC-841 monotherapy is anticipated in 2025. Dr. Hamm commented, “ ...

7. biospace.com biospace.com/press-releases/oncoc4-announces-first-patient-dosed-in-phase-1-trial-for-novel-siglec10-immune-checkpoint-inhibitor-onc-841-for-solid-tumors

OncoC4 Announces First Patient Dosed in Phase 1 Trial ... Initial data on the safety, pharmacokinetics, and clinical activity of ONC-841 monotherapy are expected in 2025. Dr. Hamm added, “It is very ...