Primary MyelofibrosisPhase 1NCT06343805
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)
A Phase 1 study testing LY5830966 in people with Primary Myelofibrosis, run by Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company at 21 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Myelofibrosis
- What is being tested?
- LY5830966
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 256 participants
- Where
- 21 sitesin 5 countries
- Study dates
- 3 Oct 2024to Dec 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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%.
Trial locations and contacts
21 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 5 countries
United States13 sites, 13 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Kristen Pettit, MD, 734-647-2829
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Gabriela Hobbs, MD, 617-724-1124
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Jacqueline Garcia, MD, 617-632-1906
- Recruiting
Levine Cancer Institute
Charlotte, North Carolina, 28204
Michael Grunwald, MD, 980-442-4363
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45221
Eric Vick, MD, 513-213-3203
- Recruiting
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Uma Borate, MD, 614-685-9828
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Prithviraj Bose, MD, 713-792-7747
- Recruiting
University of Kansas Medical Center
Kansas City, Kansas, 66160
Abdulraheem Yacoub, MD
- Recruiting
David H. Koch Center for Cancer Care at Memorial Sloan Kettering
New York, New York, 10021
Raajit Rampal, MD
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
John Mascarenhas, MD, 212-241-8839
- Recruiting
Stanford Cancer Institute
Palo Alto, California, 94304
William Shomali, MD, 650-498-6000
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Stephen Oh, MD, 314-362-8814
- Recruiting
Moffitt Cancer Cancer Center
Tampa, Florida, 33612
Andrew Kuykendall, MD, 813-745-4639
Spain3 sites, 3 recruiting
- Recruiting
Hospital Clinic Barcelona
Barcelona
Ana Moreno Triguero
- Recruiting
Hospital General Universitario Gregorio Maranon
Madrid
Santiago Osorio-Prendes, MD, 0034915868443
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid
Valentin Garcia-Gutierrez
Italy2 sites, 2 recruiting
- Not yet recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
Bologna
Francesca Palandri, MD
- Not yet recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
Francesco Passamonti, MD
United Kingdom2 sites, 2 recruiting
- Not yet recruiting
Guy's Hospital
London, UK
Claire Harrison, MD, 07939059512
- Not yet recruiting
Genesis Cancer Care UK Limited - Oxford
Oxford, UK
Adam Mead, MD
France1 site, 1 recruiting
- Recruiting
AP-HP Hopital Saint-Louis
Paris
Jean-Jacques Kiladjian
About this study
Official title: A Phase 1, Open-Label Study of LY5830966, a Type II JAK2 Inhibitor, in Patients With Myelofibrosis Previously Treated With a Type I JAK2 Inhibitor, JAK2 Inhibitor-Naïve Myelofibrosis, or High-risk Relapsed/Refractory Polycythemia Vera
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.
Read the detailed description
This is a phase 1, non-randomized, open-label study utilizing a 3+3 sequential dose escalation design followed by an expansion phase. The primary objective will be to evaluate the safety and tolerability of LY5830966 and establish a Maximally Tolerated Dose (MTD) and/or inform the establishment of a candidate Recommended Phase 3 dose (RP3D). The RP3D may be the maximally tolerated dose (MTD) or may be a dose below the MTD. The candidate RP3D will be based on adverse event (AE) pattern, pharmacokinetics (PK) and biomarker information, in addition to all available safety and efficacy data. Expansion cohorts will be enrolled to gather additional safety and efficacy information and to further refine input for future RP3D discussions. Eligible participants will have PMF, PPV-MF or PET-MF and will have either have relapsed after a response, or be refractory to, at least one prior type I JAK2 inhibitor therapy, either administered as monotherapy or in combination with another drug.
- Conditions
- Primary Myelofibrosis
- Being tested
- LY5830966
- Keywords
- Post-Essential Thrombocythemia Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, PMF, PPV-MF, PET-MF
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY5830966Drug
Also called AJ1-11095
Type II JAK2 Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Dose A of LY5830966 taken orally by participants. Receives: Drug: LY5830966 |
| Cohort 2 | Experimental | Dose B of LY5830966 taken orally by participants. Receives: Drug: LY5830966 |
| Cohort 3 | Experimental | Dose C of LY5830966 taken orally by participants. Receives: Drug: LY5830966 |
| Cohort 4 | Experimental | Dose D of LY5830966 taken orally by participants. Receives: Drug: LY5830966 |
| Cohort 5 | Experimental | Dose E of LY5830966 taken orally by participants. Receives: Drug: LY5830966 |
| Dose Expansion Cohort 1 | Experimental | Candidate RP3D of LY5830966 taken orally by participants. Receives: Drug: LY5830966 |
| Dose Expansion Cohort 2 | Experimental | Alternative candidate RP3D of LY5830966 taken orally by participants. Receives: Drug: LY5830966 |
| Dose Exploration Cohort 1 | Experimental | Dose F of LY5830966 taken orally by participants Receives: Drug: LY5830966 |
| Dose Exploration Cohort 2 | Experimental | Dose G of LY5830966 taken orally by participants Receives: Drug: LY5830966 |
| Dose Exploration Cohort 3 | Experimental | Dose H of LY5830966 taken orally by participants[ Receives: Drug: LY5830966 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Treatment Emergent AEs will be assessed during routine study visits and compared to Baseline to continuously evaluate safety and tolerability of LY5830966.
Measured: Baseline through study completion, an average of 1 year
Number of patients with Dose Limiting Toxicities (DLTs)
Protocol-defined potential DLTs will be assessed by the Safety Review Committee at routine intervals.
Measured: Baseline through study completion, an average of 1 year
To establish the maximum tolerated dose (MTD) and/or recommended phase 3 dose (RP3D) of LY5830966
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.
Measured: Baseline through study completion, an average of 1 year
Secondary outcomes (8)
To assess clinical response to LY5830966 evaluated by the Total Symptom Score (TSS).
Number and proportion of patients with an improvement of ≥50% from Baseline in Total TSS as well as time to TSS response and duration of TSS response using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. The TSS is a 7 question assessment form with lower scores indicating better outcomes.
Measured: Baseline through Week 24
To assess clinical response to LY5830966 evaluated by spleen volume assessments.
Spleen volume reduction (SVR) of ≥35% from Baseline measured by magnetic resonance imaging (MRI) or computed tomography (CT).
Measured: Baseline through Week 24
To assess clinical response to LY5830966 evaluated by spleen length assessments.
Proportion of subjects with ≥50% reduction in length of spleen assessed by palpation.
Measured: Baseline through Week 24
To assess clinical response to LY5830966 evaluated through spleen size improvement.
Time to spleen size improvement response measured by patient and across all patients.
Measured: Baseline through Week 24
To evaluate the Area Under the Curve (AUC) of LY5830966
AUC time curve from 0 to 24 hrs post dose and percent difference between intervals will be evaluated.
Measured: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the Cmax of LY5830966
The maximum observed plasma concentration will be evaluated.
Measured: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the Tmax of LY5830966
The duration of time taken to reach Cmax will be evaluated.
Measured: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the half-life of LY5830966
The depletion of AJ1-00195 in the body will be observed over time.
Measured: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2024
- Study start3 Oct 2024
- Primary completionJun 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary MyelofibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This dose escalation study will follow a 3+3 cohort design until the RP3D and/or MTD is determined.
- Masking
- None (open label)
- Enrolment
- 256 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Mascarenhas, M.D., Principal investigator, Mt. Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06343805
- Sponsor's protocol ID
- 27978
- Other IDs
- 2025-522033-64-00, J8G-MC-JDIA, AJX-101, 2025
- Status last verified
- Oct 2026
- First submitted
- 13 Mar 2024
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No