Clinical trial NCT06950034: A Phase 1 Study of STX-0712 in Patients With Advanced Hematological Malignancies (CMML and AML)
Official title: A Phase 1, Open-Label, Dose Escalation and Expansion Study of STX-0712 in Patients With Advanced Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Myelomonocytic Leukemia
Chronic Myelomonocytic Leukemia (CMML)
Chronic Myelomonocytic Leukemia-1
Chronic Myelomonocytic Leukemia-2
Refractory Chronic Myelomonocytic Leukemia
CMML
Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML)
Acute Myeloid Leukemia Post Cytotoxic Therapy
Acute Myeloid Leukemias
Refractory Acute Myeloid Leukemia (AML)
Acute Monocytic Leukemia
Keywords: refractory/resistant CMML
CMML
AML
monocytic AML
Relapsed/refractory AML
monocytic-predominant AML
Chronic Myelomonocytic Leukemia
Acute Myeloid Leukemia
Refractory Chronic Myelomonocytic Leukemia
Refractory Acute Myeloid Leukemia
Lead sponsor: Solu Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2025-04-29
Enrollment: 105
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 is a Dose Escalation and Dose expansion study testing STX-0712 in 2 indications: CMML (Cohort 1) and Monocytic and/or monocytic predominant AML (Cohort 2).
Primary purpose: TREATMENT

Brief summary: This is a first-in-human, multicenter, open-label, phase 1 study to evaluate the safety, PK, PD and preliminary efficacy of STX-0712 in patients with advanced CMML and AML for whom there are no further treatment options known to confer clinical benefit.

Detailed description: This is an open-label, non-randomized phase 1 trial to assess the safety and preliminary efficacy of STX-0712 in refractory/resistant CMML and relapsed/refractory monocytic or monocytic-predominant AML. The study will be conducted in two parts: Dose Escalation (Part 1) and Dose Expansion (Part 2). Dose Escalation will accrue CMML and AML patients across 2 cohorts using the BOIN adaptive design, followed by Dose Expansion in both cohorts using Simon's 2-Stage Design. Cohort 1 will enroll approximately 3-6 CMML patients at each dose level. After at least two dose levels have been deemed safe in Cohort 1, the Sponsor may decide to open Cohort 2 to enroll AML patients. Approximately 20 patients will be enrolled in each Dose Expansion cohort. All eligible participants will be administered the study drug, STX-0712, as a single intravenous (IV) infusion every 21 days. Patients will remain on study therapy until treatment discontinuation criteria are met.

Eligibility criteria: Inclusion Criteria:

* Refractory/resistant CMML, defined as: Diagnosis of CMML 1 or 2; and has not responded to at least 4 cycles of hypomethylating agents (HMAs)(for myeloproliferative CMML - HMAs or hydroxyurea) or discontinued prior to 4 cycles due to toxicity or has progressive disease OR
* Relapsed/refractory monocytic or monocytic predominant AML. Monocytic predominant AML is defined as ≥50% monocytes and/or monocytic precursors (promonocytes/monoblasts) and expressing at least two monocytic markers including CD4, CD11c, CD14, CD36, or CD64; and peripheral blood white blood cell (WBC) \<30,000/µL (microliters) and \<20% circulating blasts.
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
* Life expectancy of \>2 months and stable enough to complete two cycles of STX-0712, in the opinion of the Investigator.
* Adequate organ function.
* Both females of child-bearing potential and males must agree to use acceptable contraceptive methods for the duration of time in the study and to continue to use acceptable contraceptive methods for 90 days after last STX-0712 infusion.
* Able to understand and willing to sign a written informed consent form.
* Willing and able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

* Has any of the following disease-specific conditions: For CMML: Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes other than CMML. For AML: Acute Promyelocytic Leukemia (APL) or Isolated extramedullary disease.
* Eligible for an immediate allogenic stem cell transplant (alloSCT).
* Current active use of nicotine products including tobacco, nicotine patches or vaping products.
* Prior bone marrow transplant (BMT) within 6 months of date of consent; or transplanted patients who received the last dose of immunosuppressive therapies within 3 months of date of consent.
* Has active autoimmune condition requiring immunosuppressive treatment or is receiving immunosuppressive therapy for the treatment of autoimmune disorders, allergies, or other clinical symptoms. Systemic steroids \<10 mg (milligrams) daily of prednisone equivalent are allowed; and intermittent use of bronchodilators or inhaled steroids, local steroid injections, topical steroids are allowed.
* Received treatment with chemotherapy, biologic therapy, or wide-field radiation within 14 days of consent. Exceptions for hydroxyurea: For CMML and AML participants, hydroxyurea may be continued up to 72 hours prior to first dose of STX-0712. Hydroxyurea will also be permitted for first cycle of STX-0712 treatment for participants with proliferative CMML or AML with high white blood count (WBC ≥25,000/µL).
* Received an investigational treatment within 30 days prior to dosing with STX-0712.
* Received Granulocyte Colony Stimulating Factor \[G-CSF\], Granulocyte Macrophage Colony Stimulating Factor \[GM-CSF\], erythropoietin, romiplostim, or other growth factors within 2 weeks prior to first dose of STX- 0712.
* Received a live or live attenuated vaccine within 30 days before the first dose of STX-0712.
* Clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure, uncontrolled or unstable chest pain, history of heart attack(s), or stroke within 6 months prior to consent, uncontrolled high blood pressure, or clinically significant arrhythmias not controlled by medication).
* QT interval corrected by Fridericia's formula (QTcF) \>470 msec for both men and women on Screening electrocardiogram(s) (ECG). Patients with a bundle branch block must have QT interval corrected for bundle branch block.
* Other than AML or CMML, active malignancy and/or cancer history that requires active therapy. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, or organ-confined prostate cancer with no evidence of progressive disease.
* Active, uncontrolled bacterial, fungal, or viral infection.
* Known human immunodeficiency virus (HIV).
* Active or chronic hepatitis B or hepatitis C infection.
* Evidence of any other severe or uncontrolled systemic diseases, any other serious and/or unstable pre-existing medical conditions, psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator.

Primary outcomes:
measure: To determine the maximum tolerated dose (MTD) and/or minimum effective dose (MED)
timeFrame: Until the end of Dose Escalation (approximately 12 months)
Secondary outcomes:
measure: To evaluate the overall safety and tolerability of STX-0712
timeFrame: Until the end of the study (approximately 24 months)
measure: To evaluate the initial anti-tumor activity of STX-0712 in the CMML and AML cohorts
timeFrame: Until the end of the study (approximately 24 months)
measure: To evaluate the initial anti-tumor activity of STX-0712 in the CMML and AML cohorts
timeFrame: Until the end of the study (approximately 24 months)
measure: Pharmacokinetics of STX-0712: maximum concentration (Cmax)
timeFrame: Until the end of the study (approximately 24 months)
measure: Pharmacokinetics of STX-0712: time to reach maximum concentration (Tmax)
timeFrame: Until the end of the study (approximately 24 months)
measure: Pharmacokinetics of STX-0712: area under the curve (AUC)
timeFrame: Until the end of the study (approximately 24 months)
measure: Pharmacokinetics of STX-0712: half-life (t½)
timeFrame: Until the end of the study (approximately 24 months)
measure: To characterize the PD profile of STX-0712 after single and repeat-dose administration
timeFrame: Until the end of the study (approximately 24 months)
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Solu Therapeutics
name: Chief Medical Officer, MD, MSc, MBA
role: STUDY_DIRECTOR
References: