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)

Phase 1RecruitingNCT06343805

Ajax Therapeutics, Inc.76 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Myelofibrosis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (13)

Stanford Cancer Institute

Palo Alto, California, United States

RECRUITING

Moffitt Cancer Cancer Center

Tampa, Florida, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

RECRUITING

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

New York, New York, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, United States

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline through study completion, an average of 1 year

Secondary Outcomes

To assess clinical response to AJ1-11095 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.

Time frame: Baseline through Week 24

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

Spleen volume reduction (SVR) of ≥35% from Baseline measured by magnetic resonance imaging (MRI) or computed tomography (CT).

Time frame: Baseline through Week 24

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

Proportion of subjects with ≥50% reduction in length of spleen assessed by palpation.

Time frame: Baseline through Week 24

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

Time to spleen size improvement response measured by patient and across all patients.

Time frame: Baseline through Week 24

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

AUC time curve from 0 to 24 hrs post dose and percent difference between intervals will be evaluated.

Time frame: 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).

To evaluate the Cmax of AJ1-11095

The maximum observed plasma concentration will be evaluated.

Time frame: 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).

To evaluate the Tmax of AJ1-11095

The duration of time taken to reach Cmax will be evaluated.

Time frame: 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).

To evaluate the half-life of AJ1-11095

The depletion of AJ1-00195 in the body will be observed over time.

Time frame: 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).

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)

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts