ONC-841 for Cancer

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Tianhong Li

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: OncoC4, Inc.

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

Disqualifiers: Active brain metastases, Cardiovascular, Infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a Phase I open label, dose-escalation study of intravenous (IV) infusion of ONC-841 as a single agent in patients with advanced/metastatic solid tumors. The study will evaluate seven dose levels of ONC-841 starting from 0.03 mg/kg to 30 mg/kg.

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.

What safety data exists for ONC-841 or similar treatments?

The safety data for treatments similar to ONC-841, such as PD-1/PD-L1 inhibitors, show that while they can reduce the risk of some treatment-related side effects compared to chemotherapy, they may increase the risk of immune-related side effects. It's important to monitor for serious adverse events and work with healthcare providers to manage any side effects. ^{1 2 3 4 5}

How is the drug ONC-841 different from other cancer treatments?

ONC-841 is unique because it targets the transcription factor SIX1, which is involved in cancer progression by affecting tumor invasion, immune response, and cancer stem cell characteristics. This approach is novel as it aims to modulate the tumor environment and immune system, potentially offering a new avenue for cancer therapy. ^{6 7 8 9 10}

Research Team

Tianhong Li

Principal Investigator

University of California, Davis

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• ONC-841 (Virus Therapy)

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

2. India 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. [2020]

3. England 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. [2021]

4. England 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. [2022]

5. Switzerland 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. [2021]

6. India pubmed.ncbi.nlm.nih.gov

SIX1 overexpression in diffuse-type and grade III gastric tumors: Features that are associated with poor prognosis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Inhibition of Six1 affects tumour invasion and the expression of cancer stem cell markers in pancreatic cancer. [2023]

8. China pubmed.ncbi.nlm.nih.gov

Homeoprotein SIX1 compromises antitumor immunity through TGF-β-mediated regulation of collagens. [2023]

9. England 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. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibition of Six1 promotes apoptosis, suppresses proliferation, and migration of osteosarcoma cells. [2021]