JZP815 / Jazz, Redx - LARVOL DELTA

Phase I, open-label, first-in-human (FIH) study of JZP815 in advanced or metastatic solid tumors harboring mitogen-activated protein kinase (MAPK) alterations (ESMO 2023) - P1 | "2022; 82:2677. https://doi.org/10.1158/1538-7445.AM2022-2677"

Clinical • Metastases • P1 data • Melanoma • Oncology • Solid Tumor • BRAF • NRAS

A Study of JZP815 Oral Capsules in Adult Participants With Advanced or Metastatic Solid Tumors Harboring Mitogen Activated Protein Kinase (MAPK) Pathway Alterations to Investigate the Safety, Dosing, and Antitumor Activity of JZP815 (clinicaltrials.gov) - P1 | N=98 | Active, not recruiting | Sponsor: Jazz Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=332 ➔ 98

Enrollment change • Enrollment closed • First-in-human • Colorectal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • NRAS

Evaluating a novel pan-RAF inhibitor in RAS mutant and BRAF/MEK inhibitor-resistant anaplastic thyroid carcinoma (AHNS 2026) - "Mice with MDA-ATC1-R, were treated with V, 30 mg/kg QD dabrafenib + 0.5 mg/kg QD trametinib (DT), DT QD + J BID (DTJ), or DT alone QD followed by introduction of J BID as salvage (s) therapy once tumors reached 500mm3 (DTJs). This is one of the first reported studies to evaluate and compare a novel pan-RAF inhibitor JZP815 to SoC therapy for ATC in a pre-clinical setting. We demonstrated strong therapeutic potential in both NRAS_Q61K mutant and BRAFm ATC tumors that have acquired resistance to BRAF/MEK inhibitors. This work warrants further investigation and remains promising for translation to early-phase clinical trials in ATC."

Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

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 profile of MAPK inhibition (AACR 2025) - P1 | "JZP815 elicits a clinically verified PD profile that could be used to confirm target engagement in patients. JZP815 is currently in phase 1 testing (NCT05557045)."

Gene expression profiling • Monotherapy • Melanoma • Oncology • Solid Tumor • BRAF • KRAS • NRAS

Preclinical evaluation of the pan-RAF inhibitor JZP815 in Anaplastic Thyroid Carcinoma cell lines and Patient-derived Xenografts (ATA 2025) - "Although BRAF/MEK inhibition (dabrafenib and trametinib) drastically improved OS in patients with BRAFV600E-mutant (BRAFm) tumors, the latter only comprise 40% of ATC cases. We report on one of the first effective uses of a pan-RAF inhibitor in established ATC PDX models harboring either a BRAF or RAS driver mutation, with minimal in vivo toxicity. By targeting the RAF protein complex, the broadly applicable therapeutic potential for JZP815, through its promising antitumor activity, warrants continued preclinical evaluation in ATC."

Preclinical • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • KRAS • PI3K • TERT • TP53

Jazz Pharmaceuticals to Showcase Growing Impact in Solid Tumor Oncology Research at ESMO 2023 (PRNewswire) - "Jazz Pharmaceuticals plc...today announced that the company, along with partners, will present six abstracts including data from trials of bispecific antibody zanidatamab and Zepzelca^® (lurbinectedin), as well as the study design for a Phase 1 trial of the pan-RAF inhibitor JZP815, at the European Society for Medical Oncology (ESMO) Congress 2023, taking place in Madrid, Spain, from October 20-24, 2023."

Clinical data • Clinical protocol • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study of JZP815 Oral Capsules in Adult Participants With Advanced or Metastatic Solid Tumors Harboring Mitogen Activated Protein Kinase (MAPK) Pathway Alterations to Investigate the Safety, Dosing, and Antitumor Activity of JZP815 (clinicaltrials.gov) - P1 | N=320 | Recruiting | Sponsor: Jazz Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

A Study of JZP815 Oral Capsules in Adult Participants With Advanced or Metastatic Solid Tumors Harboring Mitogen Activated Protein Kinase (MAPK) Pathway Alterations to Investigate the Safety, Dosing, and Antitumor Activity of JZP815 (clinicaltrials.gov) - P1 | N=320 | Not yet recruiting | Sponsor: Jazz Pharmaceuticals

New P1 trial • Oncology • Solid Tumor

"#JazzPharmaceuticals and #Redx Announce #PanRAFInhibitor #JZP815 to Enter Clinical Development $JAZZ https://t.co/OYF7RvsEGi" (,@1stOncology)

Clinical

Jazz Pharmaceuticals and Redx Announce Pan-RAF Inhibitor JZP815 to Enter Clinical Development (Jazz Pharma Press Release) - "Jazz Pharmaceuticals...and Redx...announce the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for JZP815, a pan-RAF inhibitor for the treatment of solid tumors and hematologic malignancies that contain mutations in the MAPK pathway, enabling Jazz to proceed with initiating a clinical trial for JZP815. As a result, a milestone payment of USD $5 million from Jazz payable to Redx has been triggered. The milestone payment was triggered under the Agreement in which Jazz acquired Redx's pan-RAF inhibitor programme, announced on 10 July 2019....Jazz to initiate clinical development of JZP815 as a drug candidate for several types of difficult-to-treat solid tumours."

Financing • IND • Oncology • Solid Tumor

JZP815, a potent and selective pan-RAF inhibitor, demonstrates efficacy in RAF and RAS mutant tumor pre-clinical models (AACR 2022) - "JZP815 demonstrated enhanced activity when combined with inhibitors of other MAPK pathway components in both class 2 and class 3 mutant BRAF patient-derived tumor cells ex vivo, and KRAS mutant NSCLC and CRC xenografts in vivo. In summary, JZP815 is a potent and selective pan-RAF inhibitor that is orally bioavailable in multiple preclinical species with a well-behaved safety profile and pharmacokinetic properties predicted to provide drug exposure required for target engagement in humans, and therefore suitable for advancing into first-in-human trials."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ARAF • KRAS

"#JazzPharmaceuticals Nasdaq: $JAZZ + #RedxPharma LSE: $REDX announced that JZP815 significantly inhibited tumour▲, incl. inducing regression. #ACFview https://t.co/40BSQE9vBS @RedxPharma @JazzPharma @Scandion" (,@ACFER01)

Oncology

Jazz Pharmaceuticals Presents Pre-Clinical Data for Pan-RAF Inhibitor JZP815, including Pharmacokinetic Properties and Efficacy in Multiple Solid Tumor Types (PRNewswire) - "Jazz Pharmaceuticals...and collaboration partner Redx Pharma...presented data showing the pan-RAF kinase inhibitor, JZP815, was active in multiple RAF- and RAS-mutant tumor pre-clinical models, with a pharmacokinetic profile that may provide drug exposure required for target engagement in humans....Novel, investigational drug JZP815 inhibited tumor growth in several RAS- and BRAF-mutated solid tumor models, and demonstrated enhanced activity when combined with other MAPK pathway inhibitors. Jazz plans to submit an investigational new drug application (IND) for JZP815 this year."

IND • Preclinical • Oncology • Solid Tumor

Jazz Pharmaceuticals to Present Pan-RAF Inhibitor Pre-Clinical Data at American Association for Cancer Research (AACR) 2022 Annual Meeting (PRNewswire) - "Jazz Pharmaceuticals plc...announced that pre-clinical data on JZP815, an investigational, next-generation pan-RAF kinase inhibitor, will be presented as a poster at the American Association for Cancer Research (AACR) 2022 Annual Meeting from April 8-13, 2022....'Together with our pre-clinical collaboration partner, Redx Pharma, we look forward to presenting at AACR our first pre-clinical data on JZP815, which demonstrated that it selectively and potently inhibits mutant A, B and CRAF kinases, and demonstrated anti-tumor activity in RAS- and RAF-mutant xenograft models'...Jazz plans to submit an IND for JZP815 this year."

IND • Preclinical • Hematological Malignancies • Oncology • Solid Tumor