JZP815 for Cancer

Recruiting at 7 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jazz Pharmaceuticals

Must not be taking: CYP3A4 inducers/inhibitors, PPIs, H2 antagonists

Disqualifiers: Uncontrolled brain metastases, Active infections, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

332 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing JZP815, a new drug, in patients with advanced or metastatic solid tumors that have specific genetic changes. The drug works by blocking signals that promote cancer growth.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as strong or moderate inducers or inhibitors of CYP3A4, at least 4 weeks before starting the study. You also need to stop using proton pump inhibitors and histamine-2 receptor antagonists at least 2 weeks before the first dose. If you are on cancer-directed therapy, a washout period of 28 days or 5 half-lives is required.

How is the drug JZP815 different from other cancer treatments?

JZP815 is unique because it targets the JNK signaling pathway, which is involved in cell growth and cancer progression. This pathway is not commonly targeted by existing cancer treatments, making JZP815 a novel approach for potentially inhibiting cancer cell proliferation and metastasis. ^{1 2 3 4 5}

Eligibility Criteria

Adults with advanced or metastatic solid tumors that have changes in the MAPK pathway can join this trial if they've tried all standard treatments without success, are not pregnant or breastfeeding, agree to use effective contraception, and have a life expectancy of at least 12 weeks. They must be able to undergo tumor biopsies and have good organ function.

Inclusion Criteria

A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 3 days before the first dose of study intervention

Expected life expectancy of at least 12 weeks

I am 18 years old or older.

Exclusion Criteria

I do not have any severe or uncontrolled health conditions.

I have not had any cancer other than non-spreading skin cancer, early-stage prostate cancer with low PSA, or in-situ cancers in the last 2 years.

I have serious heart issues, including recent stroke or heart attack.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration (Part A)

Characterize the safety and tolerability of JZP815, assess pharmacokinetics, and determine a recommended phase 2 dose

8-12 weeks

Multiple visits for dosing and PK assessments

Expansion (Part B)

Further investigate the recommended phase 2 dose and assess antitumor activity in various subsets of disease

12-24 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• JZP815 (MAPK Pathway Inhibitor)

Trial Overview The study is testing JZP815 oral capsules for safety, proper dosing levels, and initial effectiveness against tumors. It's an early-phase trial (phase 1) focusing on patients whose cancers involve alterations in the MAPK pathway.

Participant Groups

Group I: Expansion (Part B): JZP815 Experimental Treatment 1 Intervention

Participants with advanced or metastatic solid tumors who will receive JZP815 at the RP2D established in Dose Exploration (Part A).

Group II: Dose Exploration (Part A): JZP815 Experimental Treatment 1 Intervention

Participants will receive JZP815 with a starting dose of 20 mg twice daily (BID).

Who Is Running the Clinical Trial?

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

JIP-1 is identified as a specific inhibitor of the JNK signaling pathway, which plays a crucial role in regulating cell growth and proliferation.

By causing cytoplasmic retention of JNK, JIP-1 inhibits JNK-regulated gene expression and suppresses cellular proliferation, including transformation by the Bcr-Abl oncogene, highlighting its potential as a therapeutic target in cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cytoplasmic inhibitor of the JNK signal transduction pathway. Dickens, M., Rogers, JS., Cavanagh, J., et al.[2019]

JIP-1, a scaffolding protein in the JNK signaling pathway, is co-regulated with the IGF-II gene, which is known for its growth-stimulating effects, indicating a potential role in tumor growth.

In a study of six primary Wilms tumors from pigs, high co-expression of JIP-1 and IGF-II was observed, suggesting that JIP-1 may influence IGF-II-driven tumor cell proliferation, similar to patterns seen in human Wilms tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The expression of the insulin-like growth factor II, JIP-1 and WT1 genes in porcine nephroblastoma. Engström, W., Granerus, M.[2010]

MAPK8IP2 is highly expressed in prostate cancer tissues and its overexpression is linked to worse clinical outcomes and poor prognosis, suggesting it could be a significant biomarker for diagnosis and prognosis evaluation.

In laboratory studies, reducing MAPK8IP2 levels led to decreased prostate cancer cell proliferation, migration, and invasion, indicating that targeting MAPK8IP2 may be a promising therapeutic strategy for treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAPK8IP2 is a potential prognostic biomarker and promote tumor progression in prostate cancer. Zeng, Z., He, W., Jiang, Y., et al.[2022]

JMJD2A is overexpressed in endometrial carcinoma, indicating its potential role as an oncogene in this type of cancer, as confirmed by various laboratory techniques including immunohistochemistry and quantitative PCR.

Reducing JMJD2A levels significantly decreased the proliferation, invasion, and metastasis of endometrial carcinoma cells, suggesting that targeting JMJD2A could be a promising strategy for developing new cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression and effects of JMJD2A histone demethylase in endometrial carcinoma. Wang, HL., Liu, MM., Ma, X., et al.[2019]

Jazf1 is upregulated in human prostate cancer tissues and promotes cancer cell proliferation, migration, and invasion in prostate cancer cell lines, indicating its role in cancer progression.

The mechanism by which Jazf1 enhances prostate cancer progression involves the activation of the JNK/c-Jun signaling pathway, leading to increased expression of Slug, which is associated with tumor growth and metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Jazf1 promotes prostate cancer progression by activating JNK/Slug. Sung, Y., Park, S., Park, SJ., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A cytoplasmic inhibitor of the JNK signal transduction pathway. [2019]

2. Greece pubmed.ncbi.nlm.nih.gov

The expression of the insulin-like growth factor II, JIP-1 and WT1 genes in porcine nephroblastoma. [2010]

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

MAPK8IP2 is a potential prognostic biomarker and promote tumor progression in prostate cancer. [2022]

4. Thailand pubmed.ncbi.nlm.nih.gov

Expression and effects of JMJD2A histone demethylase in endometrial carcinoma. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Jazf1 promotes prostate cancer progression by activating JNK/Slug. [2019]