JAB-30355 for Solid Tumors

Recruiting at 10 trial locations

Overseen By Jacobio Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Disqualifiers: Brain metastases, CNS tumor, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is to evaluate the efficacy and safety of JAB-30355 in adult participants with advanced solid tumors harboring TP53 Y220C mutation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What makes the drug JAB-30355 unique for treating solid tumors?

JAB-30355 is unique because it targets the Jab1/COPS5 protein, which is often overexpressed in various cancers and linked to poor prognosis. This drug may offer a novel approach by potentially interfering with cancer progression and resistance to other treatments, such as chemotherapy and radiotherapy, through its impact on DNA damage and repair pathways. ^{1 2 3 4 5}

Eligibility Criteria

Adults over 18 with advanced solid tumors that have a specific genetic change called TP53 Y220C can join. They must have at least one tumor that can be measured, good blood and organ function, and be able to take pills. Participants should have tried at least one other treatment before and be fairly active (ECOG score of 0 or 1).

Inclusion Criteria

I have at least one tumor that can be measured.

My cancer has a specific TP53 Y220C genetic mutation.

I am fully active or can carry out light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Multiple dose levels of JAB-30355 will be explored to determine the maximum tolerated dose (MTD)

Approximately 1 year

Dose Expansion

Further exploration of JAB-30355's clinical benefit and tolerability in selected dose levels

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JAB-30355

Trial Overview The trial is testing JAB-30355's effectiveness and safety in treating these tumors. It aims to see how well this new medication works for patients who carry the TP53 Y220C mutation.

Participant Groups

Group I: Dose expansion phase Experimental Treatment 1 Intervention

Dose Expansion Phase will explore JAB-30355's clinical benefit and optimal tolerability in selected dose level.

Group II: Dose escalation phase Experimental Treatment 1 Intervention

Multiple dose levels of JAB-30355 will be explored to determine the maximum tolerated dose (MTD)

Who Is Running the Clinical Trial?

Jacobio Pharmaceuticals Co., Ltd.

Lead Sponsor

Trials

21

Recruited

2,300+

Findings from Research

Jab1/COPS5 is identified as a high-risk gene associated with poor prognosis in various cancers, based on analysis of large clinical datasets including TCGA, GEO, and CPTAC, indicating its potential as a biomarker for cancer progression.

The study found that Jab1/COPS5 expression correlates with immune cell infiltration in certain tumors, suggesting it may play a role in the tumor microenvironment and could be targeted for therapeutic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pan-cancer analyses of Jab1/COPS5 reveal oncogenic role and clinical outcome in human cancer. Wang, L., Zeng, X., Yang, G., et al.[2023]

The study identifies Stat3 as an upstream regulator of Jab1/Csn5 expression in nasopharyngeal carcinoma (NPC), which contributes to the cancer's resistance to cisplatin treatment.

Silencing Stat3 in tumors reduces Jab1/Csn5 levels, making NPC cells more sensitive to cisplatin-induced apoptosis, suggesting that targeting this signaling pathway could improve treatment outcomes in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression. Pan, Y., Wang, S., Su, B., et al.[2019]

A meta-analysis of 27 studies involving 2609 cancer patients found that high levels of Jab1 expression are significantly associated with poor overall survival, indicating its potential role as a prognostic marker.

High Jab1 expression correlates with advanced cancer features such as clinical stage, lymphatic metastasis, and distant metastasis, suggesting it may contribute to cancer progression and could be targeted for therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic role of c-Jun activation domain-binding protein-1 in cancer: A systematic review and meta-analysis. Shi, D., Mu, S., Hu, B., et al.[2021]

In a study of 80 colorectal carcinoma (CRC) cases, Jab1 protein was found to be highly expressed in cancerous tissues (96.3% positive rate), indicating its potential role in the development of CRC.

The expression of Jab1 was significantly associated with important clinical features such as tumor differentiation, invasion depth, TNM stage, and lymph node metastasis, suggesting it could serve as a valuable diagnostic marker and therapeutic target for CRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression and significance of c-Jun activation domain binding protein 1 in human colorectal carcinoma]. Guo, Z., Lü, Q., Zhang, Y., et al.[2017]

Jab1/CSN5 protein is overexpressed in nasopharyngeal carcinoma (NPC) cell lines that are resistant to cisplatin and other DNA-damaging treatments, indicating its role in treatment resistance.

Knocking down Jab1 expression increases sensitivity to cisplatin and radiation, while enhancing Jab1 levels boosts resistance, suggesting that Jab1 regulates the DNA repair protein Rad51 and could serve as a biomarker for predicting treatment outcomes in NPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of Jab1/CSN5 induces radio- and chemo-sensitivity in nasopharyngeal carcinoma through changes to the DNA damage and repair pathways. Pan, Y., Zhang, Q., Atsaves, V., et al.[2021]

References

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

Pan-cancer analyses of Jab1/COPS5 reveal oncogenic role and clinical outcome in human cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Prognostic role of c-Jun activation domain-binding protein-1 in cancer: A systematic review and meta-analysis. [2021]

4. China pubmed.ncbi.nlm.nih.gov

[Expression and significance of c-Jun activation domain binding protein 1 in human colorectal carcinoma]. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Suppression of Jab1/CSN5 induces radio- and chemo-sensitivity in nasopharyngeal carcinoma through changes to the DNA damage and repair pathways. [2021]