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)

NCT06343805 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AJX-101
• Study Type: interventional
• Target: 76
• Locations: 3 countries
• Sites: 16

Brief 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.

Conditions

Post-Polycythemia Vera Myelofibrosis; PPV-MF; PET-MF; Primary Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis; PMF

Outcome Measures

Primary Outcomes (3)

• Number of patients with treatment-emergent adverse events as assessed by 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 AJ1-11095.

  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.

  Baseline through study completion, an average of 1 year

• To establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AJ1-11095

  Safety evaluations will occur consistently for each patient and across patients to assess MTD or RP2D. See description of safety evaluations described in outcomes 1 and 2 mentioned above.

  Baseline through study completion, an average of 1 year

Secondary Outcomes (8)

• To assess clinical response to AJ1-11095 evaluated by the Total Symptom Score (TSS).

  Baseline through Week 24

• To assess clinical response to AJ1-11095 evaluated by spleen volume assessments.

  Baseline through Week 24

• To assess clinical response to AJ1-11095 evaluated by spleen length assessments.

  Baseline through Week 24

• To assess clinical response to AJ1-11095 evaluated through spleen size improvement.

  Baseline through Week 24

• To evaluate the Area Under the Curve (AUC) of AJ1-11095

  Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).

Study Arms (7)

Cohort 1

EXPERIMENTAL

Dose A of AJ1-11095 taken orally by patients.

Drug: AJ1-11095

Cohort 2

EXPERIMENTAL

Dose B of AJ1-11095 taken orally by patients.

Drug: AJ1-11095

Cohort 3

EXPERIMENTAL

Dose C of AJ1-11095 taken orally by patients.

Drug: AJ1-11095

Cohort 4

EXPERIMENTAL

Dose D of AJ1-11095 taken orally by patients.

Drug: AJ1-11095

Cohort 5

EXPERIMENTAL

Dose E of AJ1-11095 taken orally by patients.

Drug: AJ1-11095

Dose Expansion Cohort 1

EXPERIMENTAL

Candidate RP2D of AJ1-11095 taken orally by patients.

Drug: AJ1-11095

Dose Expansion Cohort 2

EXPERIMENTAL

Alternative candidate RP2D of AJ1-11095 taken orally by patients.

Drug: AJ1-11095

Interventions

AJ1-11095 DRUG

Type II JAK2 Inhibitor

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Dose Expansion Cohort 1; Dose Expansion Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• Diagnosis of PMF, post-PV MF, or post-ET MF.
• DIPSS Intermediate-2 or High-risk MF with ≤10% blasts, regardless of JAK2 mutation status.
• Estimated spleen volume ≥450cm3.
• MFSAF v.4.0 TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
• 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.
• ANC ≥1.0×10\^9/L.
• Platelet count ≥75×10\^9/L.
• eGFR ≥45 mL/min/1.73m2.
• Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
• AST and ALT ≤3.0 × ULN.
• QTcF ≤480 msec.

You may not qualify if:

• Prior splenectomy.
• Splenic irradiation within 3 months prior to first dose of study drug.
• Ongoing use of systemic corticosteroids at dose equivalent to \>10mg/day of prednisone.
• Uncontrolled intercurrent illness such as an acute infection.
• Chronic active or acute hepatitis B or C infection.
• Chemotherapy in the previous 4 weeks prior to first dose of study drug (Hydrea is permitted until 5 days before starting protocol therapy).
• 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).
• Use of erythropoiesis stimulating agents (unless stable for \>8 weeks).
• Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
• Unable or unwilling to undergo CT or MRI for spleen size imaging.
• Pregnant or breastfeeding.
• Requirement for therapy with a medication that is a strong CYP3A4 inhibitor as a concomitant medication.

Sponsors & Collaborators

• Ajax Therapeutics, Inc.: lead

Study Sites (16)

Stanford Cancer Institute

Palo Alto, California, 94304, United States

RECRUITING

Moffitt Cancer Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

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

New York, New York, 10021, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45221, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

AP-HP Hopital Saint-Louis

Paris, France

RECRUITING

Hospital Clinic Barcelona

Barcelona, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, Spain

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• John Mascarenhas, M.D.

  Mt. Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Steensma, M.D.

CONTACT

917-410-7250; david@ajaxtherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This dose escalation study will follow a 3+3 cohort design until the RP2D and/or MTD is determined.

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: April 3, 2024
• Study Start: October 23, 2024
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): February 15, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); ES (2); US (13)