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NCT06343805PHASE1Recruiting

A Phase 1 Study of AJ1-11095 in Patients 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.

Start Date

10/23/2024

Completion Date

2/15/2027

Summary

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 JAK2 inhibitor, AJ1-11095, in subjects with primary or secondary myelofibrosis previously treated with at least one type I JAK2 inhibitor.

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 AJ1-11095, and establish a Maximally Tolerated Dose (MTD) and/or inform the establishment of a candidate Recommended Phase 2 dose (RP2D). The RP2D may be the maximally tolerated dose (MTD) or may be a dose below the MTD. The candidate RP2D will be based on AE pattern, 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 RP2D 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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. 18 years of age or older. 2. Diagnosis of PMF, post-PV MF, or post-ET MF. 3. DIPSS Intermediate-2 or High-risk MF with ≤10% blasts, regardless of JAK2 mutation status. 4. Estimated spleen volume ≥450cm3. 5. MFSAF v.4.0 TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3. 6. ECOG PS of 0, 1, 2, or 3. 7. Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response. 8. ANC ≥1.0×10\^9/L. 9. Platelet count ≥75×10\^9/L. 10. eGFR ≥45 mL/min/1.73m2. 11. Serum total bilirubin ≤2.0 × upper limit of normal (ULN). 12. AST and ALT ≤3.0 × ULN. 13. QTcF ≤480 msec. Exclusion Criteria: 1. Prior splenectomy. 2. Splenic irradiation within 3 months prior to first dose of study drug. 3. Ongoing use of systemic corticosteroids at dose equivalent to \>10mg/day of prednisone. 4. Uncontrolled intercurrent illness such as an acute infection. 5. Chronic active or acute hepatitis B or C infection. 6. Chemotherapy in the previous 4 weeks prior to first dose of study drug (Hydrea is permitted until 5 days before starting protocol therapy). 7. Use of a Type I JAK2 inhibitor must have been discontinued for at least 5 days or 5 half-lives prior to dosing (whichever is longer). 8. Use of erythropoiesis stimulating agents (unless stable for \>8 weeks). 9. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0). 10. Unable or unwilling to undergo CT or MRI for spleen size imaging. 11. Pregnant or breastfeeding. 12. Requirement for therapy with a medication that is a strong CYP3A4 inhibitor as a concomitant medication.

Interventions

DRUG

AJ1-11095

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Conditions

Primary MyelofibrosisPost-Essential Thrombocythemia MyelofibrosisPost-Polycythemia Vera MyelofibrosisPMFPPV-MFPET-MF

Locations

Stanford Cancer Institute

Palo Alto, California 94304

United States

Moffitt Cancer Cancer Center

Tampa, Florida 33612

United States

University of Kansas Medical Center

Kansas City, Kansas 66160

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02115

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

David H. Koch Center for Cancer Care at Memorial Sloan Kettering

New York, New York 10021

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

Levine Cancer Institute

Charlotte, North Carolina 28204

United States

University of Cincinnati

Cincinnati, Ohio 45221

United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

AP-HP Hopital Saint-Louis

Paris,

France

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola

Bologna, Italy

Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Italy

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Spain

Hospital Clinic Barcelona

Barcelona,

Spain

Hospital Universitario Ramon y Cajal

Madrid,

Spain

Guy's Hospital

London, UK

United Kingdom

Genesis Cancer Care UK Limited - Oxford

Oxford, UK

United Kingdom