A Phase 1 Study of LY5830966 in Participants With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i)
Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company
Phase
Phase 1
Started
2024-10-23
Last updated
2026-09-17
Condition(s) studied
Primary Myelofibrosis
Investigational drug(s) / intervention(s)
LY5830966
LY5830966: Type II JAK2 Inhibitor
Study summary
J8G-MC-JDIA (AJX-101) is a first-in-human (FIH), phase 1, non-randomized, multi-center, open-label clinical trial designed to investigate the safety, tolerability, pharmacokinetics (PK), clinical activity and changes in biomarkers of an orally administered type II Janus Kinase 2 (JAK2) inhibitor, LY5830966, in participants with primary or secondary myelofibrosis previously treated with at least one type I JAK2 inhibitor.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Diagnosis of PMF, post-PV MF, or post-ET MF.
* Dynamic International Prognostic Scoring System (DIPSS) Intermediate-1, Intermediate-2 or High-risk MF with less than or equal to (≤)10% blasts, regardless of JAK2 mutation status.
* Estimated spleen volume greater than or equal to (≥)450 cubic centimeter (cm ³)
* Myelofibrosis Symptom Assessment Form, version 4.0 (MFSAF v.4.0) TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
* Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1, 2, or 3.
* Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response.
* Absolute neutrophil count greater than or equal to 1,000 per microliter of blood (ANC ≥1.0×10\^9/L).
* Platelet count ≥75×10\^9/L.
* Estimated glomerular filtration rate greater than or equal to 45 milliliters per minute per 1.73 square meters (eGFR ≥45 mL/min/1.73m²).
* Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit normal (ULN).
* QTcF ≤470 msec.
Polycythemia vera (PV) Only
* Confirmed diagnosis of PV
* Participants must have high-risk disease as defined by 60 years of age or older and/or have prior history of thrombotic event
* R/R or intolerant to at least one line of prior therapy including but not limited to interferon-based therapies, ruxolitinib, or hydroxyurea (HU) as defined by European LeukemiaNet (ELN) criteria
Exclusion Criteria:
* Prior splenectomy or splenic irradiation within 3 months.
* Ongoing use of systemic corticosteroids at dose equivalent to greater than (\>) 20 milligrams per day (mg/day) of prednisone.
* Active, uncontrolled systemic infection or active Hepatitis B or C
* Chemotherapy in the previous 4 weeks or prior JAK2 inhibitor not discontinued per required washout prior to first dose
* Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
* Pregnant or breastfeeding: males planning to father a child during treatment and for 3 months after last dose.
* Requirement for therapy with a medication that is a strong Cytochrome P450 3A4 CYP3A4 inhibitor as a concomitant medication.
* Currently on an interventional therapeutic trial in the treatment phase.
* Significant cardiovascular disease
* Active second primary malignancy (or diagnosed within 2 years) at high risk of progression, with standard exceptions (treated skin cancer, in situ cervical cancer, curatively treated localized breast/prostate cancer)
* Prolongation of the corrected QTcF ≥470 millisecond during screening
* Individual with a history of (noninfectious) pneumonitis/interstitial lung disease.
First line (1L) MF only:
* Prior treatment with JAK2 inhibitors
High-risk R/R PV only:
* Prior PV-directed therapy without required washout
* Active or chronic bleeding within 2 months prior to enrollment
* Clinically significant thrombosis (e.g., pulmonary embolism, deep vein thrombosis, or splenic vein thrombosis) within 2 months prior to enrollment
* Requires phlebotomy at hematocrit levels \<45%.
Primary outcome measure(s)
Number of patients with treatment-emergent adverse events (TEAEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0). — Baseline through study completion, an average of 1 year Treatment Emergent AEs will be assessed during routine study visits and compared to Baseline to continuously evaluate safety and tolerability of LY5830966.
Number of patients with Dose Limiting Toxicities (DLTs) — Baseline through study completion, an average of 1 year Protocol-defined potential DLTs will be assessed by the Safety Review Committee at routine intervals.
To establish the maximum tolerated dose (MTD) and/or recommended phase 3 dose (RP3D) of LY5830966 — Baseline through study completion, an average of 1 year Safety evaluations will occur consistently for each patient and across patients to assess MTD or RP3D. See description of safety evaluations described in outcomes 1 and 2 mentioned above.
Trial sites (21)
Facility
City
Region
Status
Stanford Cancer Institute
Palo Alto
California
Recruiting
Moffitt Cancer Cancer Center
Tampa
Florida
Recruiting
University of Kansas Medical Center
Kansas City
Kansas
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana Farber Cancer Institute
Boston
Massachusetts
Recruiting
University of Michigan
Ann Arbor
Michigan
Recruiting
Washington University School of Medicine
St Louis
Missouri
Recruiting
David H. Koch Center for Cancer Care at Memorial Sloan Kettering
New York
New York
Recruiting
Icahn School of Medicine at Mount Sinai
New York
New York
Recruiting
Levine Cancer Institute
Charlotte
North Carolina
Recruiting
University of Cincinnati
Cincinnati
Ohio
Recruiting
The Ohio State University Comprehensive Cancer Center
Columbus
Ohio
Recruiting
MD Anderson Cancer Center
Houston
Texas
Recruiting
AP-HP Hopital Saint-Louis
Paris
France
Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
Bologna
Italy
Not Yet Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
Italy
Not Yet Recruiting
Hospital General Universitario Gregorio Maranon
Madrid
Spain
Recruiting
Hospital Clinic Barcelona
Barcelona
Spain
Recruiting
Hospital Universitario Ramon y Cajal
Madrid
Spain
Recruiting
Guy's Hospital
London
UK
Not Yet Recruiting
Genesis Cancer Care UK Limited - Oxford
Oxford
UK
Not Yet Recruiting
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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