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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called JZP815 for individuals with advanced or metastatic solid tumors. The researchers aim to determine the safety of JZP815, identify the optimal dosage, and assess its initial effectiveness against tumors. The trial consists of two parts: one to explore doses and another to expand on the results. Ideal candidates for this trial have a solid tumor with specific changes in the MAPK pathway and have exhausted all standard treatments without success. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that JZP815 is likely to be safe for humans?

In earlier studies, JZP815 showed promising results in animals, slowing down and even reversing tumor growth in mice. While encouraging, it's important to note that the study is still in the early stages for humans. Currently, researchers are focusing on the safety of JZP815 for people and how well the body tolerates it. As this trial is in its first phase, the drug is being administered to humans for the first time to identify any side effects. Although there is limited information on human reactions, this phase will provide crucial safety data as testing continues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about JZP815 for cancer treatment because it targets specific genetic mutations in cancer cells, potentially offering a more personalized approach than traditional chemotherapy or radiation. Unlike most treatments that attack both healthy and cancerous cells, JZP815 aims to inhibit the abnormal proteins driving tumor growth, which could lead to fewer side effects and improved outcomes. This precision targeting is a significant advancement in treating advanced or metastatic solid tumors, offering hope for patients who may not respond to existing therapies.

What evidence suggests that JZP815 might be an effective treatment for cancer?

Research has shown that JZP815, a pan-RAF inhibitor, may help treat solid tumors. In studies with mice, JZP815 significantly slowed tumor growth and even caused some tumors to shrink. This drug targets specific genetic changes in tumors, particularly those related to the MAPK pathway, which plays a role in cancer growth. JZP815 has proven effective against certain tumors with KRAS and NRAS mutations, suggesting it could potentially treat these cancers. These early results are promising and indicate that JZP815 might work in humans with similar tumors. Participants in this trial will receive JZP815, with some in the Dose Exploration phase and others in the Expansion phase, to further evaluate its effectiveness and safety. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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

Must have measurable disease by RECIST v1.1

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• JZP815

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. investor.jazzpharma.com investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-presents-pre-clinical-data-pan-raf

Jazz Pharmaceuticals Presents Pre-Clinical Data for Pan-RAF ... JZP815 significantly inhibited tumor growth, including inducing tumor regression, as a single agent in multiple mouse xenograft solid tumor ...

2. prnewswire.com prnewswire.com/news-releases/jazz-pharmaceuticals-presents-pre-clinical-data-for-pan-raf-inhibitor-jzp815-including-pharmacokinetic-properties-and-efficacy-in-multiple-solid-tumor-types-301520973.html

Jazz Pharmaceuticals Presents Pre-Clinical Data for Pan ... JZP815 significantly inhibited tumor growth, including inducing tumor regression, as a single agent in multiple mouse xenograft solid tumor ...

3. withpower.com withpower.com/trial/phase-1-tumors-solid-8-2022-f1382

JZP815 for Cancer · Recruiting Participants for Phase ... This trial is testing JZP815, a new drug, in patients with advanced or metastatic solid tumors that have specific genetic changes.

4. researchgate.net researchgate.net/publication/391001068_Abstract_6830_JZP815_a_potent_and_selective_pan-RAF_inhibitor_is_effective_against_a_spectrum_of_mutant_KRAS_and_NRAS_solid_tumor_cancers_as_monotherapy_and_in_combination_generating_a_gene_expression

Abstract 6830: JZP815, a potent and selective pan-RAF ... JZP815, a potent and selective pan-RAF inhibitor, is effective against a spectrum of mutant KRAS and NRAS solid tumor cancers, as monotherapy ...

5. investor.jazzpharma.com investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-present-pan-raf-inhibitor-pre-clinical-data

Jazz Pharmaceuticals to Present Pan-RAF Inhibitor Pre ... The Jazz presentation abstract – titled, "JZP815, a potent and selective pan-RAF inhibitor, demonstrates efficacy in RAF and RAS mutant tumor ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/pan-raf-inhibitor-jzp815?pn=1

Clinical Trials Using pan-RAF Inhibitor JZP815 - NCI A Study of JZP815 Oral Capsules in Adult Participants With Advanced or Metastatic Solid Tumors ... Safety, Dosing, and Antitumor Activity of JZP815. Status ...

7. clinicaltrial.be clinicaltrial.be/en/details/14505?per_page=100&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

A Study of JZP815 Oral Capsules in Adult Participants Wit... This first-in-human study will consist of two parts: Part A and Part B. Part A will characterize the safety and tolerability of JZP815, ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10167

A Study of JZP815 Oral Capsules in Adult Participants ... This phase 1 study will investigate the safety, dosing, and initial antitumor activity of JZP815 in participants with advanced or metastatic solid tumors.