Clinical trial NCT06343805: 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)
Official title: A Multicenter, Open-Label, Phase 1 Study of AJ1-11095 Administered as Oral Monotherapy 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Primary Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
PMF
PPV-MF
PET-MF
Lead sponsor: Ajax Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-03
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This dose escalation study will follow a 3+3 cohort design until the RP2D and/or MTD is determined.
Primary purpose: TREATMENT

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.

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: 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 JAK2 inhibitor in the previous 10 days.
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.

Primary outcomes:
measure: Number of patients with treatment-emergent adverse events as assessed by CTCAE v 5.0.
timeFrame: Baseline through study completion, an average of 1 year
measure: Number of patients with Dose Limiting Toxicities (DLTs)
timeFrame: Baseline through study completion, an average of 1 year
measure: To establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AJ1-11095
timeFrame: Baseline through study completion, an average of 1 year
Secondary outcomes:
measure: To assess clinical response to AJ1-11095 evaluated by the Total Symptom Score (TSS).
timeFrame: Baseline through Week 24
measure: To assess clinical response to AJ1-11095 evaluated by spleen volume assessments.
timeFrame: Baseline through Week 24
measure: To assess clinical response to AJ1-11095 evaluated by spleen length assessments.
timeFrame: Baseline through Week 24
measure: To assess clinical response to AJ1-11095 evaluated through spleen size improvement.
timeFrame: Baseline through Week 24
measure: To evaluate the Area Under the Curve (AUC) of AJ1-11095
timeFrame: 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).
measure: To evaluate the Cmax of AJ1-11095
timeFrame: 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).
measure: To evaluate the Tmax of AJ1-11095
timeFrame: 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).
measure: To evaluate the half-life of AJ1-11095
timeFrame: 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).
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Cancer Center
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Mt. Sinai
name: John Mascarenhas, M.D.
role: PRINCIPAL_INVESTIGATOR
References: