Safety and Effectiveness of ABM-168 in Adults with Advanced Solid Tumors.

Stopped early · Phase 1

Conditions studied: Advanced Solid Tumor, RAS Mutation, RAF Mutation, NF1 Mutation

In brief

This is a Phase 1, First-in-Human (FIH), open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ABM-168 in adult patients with RAS or RAF or NF-1 mutated advanced solid tumors as ABM-168 may have a significant effect in inhibiting cell growth.

Key facts

Study ID

NCT05831995

Run by

ABM Therapeutics Corporation

People needed

12

Starts

2023-03-30

Expected to finish

2024-06-30

Last updated by the study team

2024-12-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male and female subjects age 18 years and older who are able to sign informed consent and comply with the protocol
• Patients with histologically or cytologically documented, locally advanced, or metastatic solid tumor malignancy that has either:
• failed prior standard therapy; or
• exhausted all existing standard therapy; or
• standard therapy is not considered appropriate per subject and/or investigator. No limitation on the lines of previous standard therapy received.
• Patients with asymptomatic or symptomatic but stable brain metastases or CNS primary malignancies who meet following criteria specifically:
• Asymptomatic, brain metastases or primary CNS tumors;
• Stable symptomatic brain metastases or CNS primary tumors not requiring steroids treatment or receiving steroids treatment (dexamethasone or equivalent) with total daily dosage no more than 4 mg, with a stable or reduced dosage of steroids within 2 weeks prior to the planned first dose
• ECOG performance score of 0 or 1, or Karnofsky performance score of ≥ 70.
• ≥ 3 months life expectancy
• Receiving no blood transfusions or granulocyte colony-stimulating factor (G-CSF) or other hematopoietic stimulating factors within 2 weeks prior to the planned first dosing. Adequate organ function confirmed at screening as evidenced by:
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L
• Hemoglobin (Hgb) ≥ 90 g/dL
• Platelets (Plt) ≥ 75 ×10\^9/L
• AST/ALT ≤ 2.5 × Upper Limit of Normal (ULN) or ≤ 5.0 × ULN if liver metastases are present
• Total bilirubin ≤ 1.5 × ULN, or direct bilirubin < ULN (for patients with total bilirubin levels >1.5 ×ULN)
• Calculated creatinine clearance ≥ 60 mL/min
• International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, if received no anti-coagulation medication(s); INR ) ≤ ULN, if received anti-coagulation medication(s).
• Average QTcF ≤ 470 ms per Fridericia formula
• Negative Hepatitis B Surface Antigen (HBsAg) at screening, or positive HBsAg with HBV DNA below LLN.
• Notes: Manage HBsAg positive subject according to the institutional standard practices (i.e., monitor HBV DNA, prescribe anti-HBV therapy as needed, etc.)
• Hepatitis C Virus (HCV) viral load below limit of quantification at screening, or positive HCV antibody with negative HCV-RNA.
• Notes: Only conduct HCV antibody and/or HCV-RNA assay in the subjects with prior history of HCV infection.
• Negative HIV at screening, or patients with prior history of HIV infection, CD4+ T-cell (CD4+) counts ≥ 350 cells/μL and without a history of AIDS-defining opportunistic infections.
• Negative serum pregnancy test within 72 hours before starting study treatment in all pre-menopausal women and women < 12 months after the onset of menopause

You may not qualify if…

• Women who are pregnant or breast-feeding.
• Have leptomeningeal disease (LMD).
• Have a history of stroke within 6 months prior to the first dose.
• Have impaired cardiac function or clinically significant cardiovascular disease(s) including but not limited to any of the following:
• Left ventricular ejection fraction (LVEF) < 50% as determined by cardiac ultrasound.
• Congenital long QT syndrome.
• Grade 2 type II AV block or grade 3 AV block.
• Unstable angina within 6 months prior to the first dose.
• Acute myocardial infarction within 6 months prior to the first dose.
• ≥ Class III heart failure per New York Heart Association (NYHA) functional classification within 6 months prior to the first dose.
• ≥ CTCAE Grade 2 ventricular arrhythmia within 6 months prior to study initiation.
• Have uncontrolled hypertension at screening, with systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg after receiving anti-hypertension treatment.
• Have unresolved ≥ CTCAE Grade 2 diarrhea at the time of the first dose; or have gastrointestinal impairment conditions or diseases that significantly alter ABM-168 absorption at screening per investigator (e.g., ulcerative disease, poorly controlled nausea, vomiting, malabsorption syndrome, or small intestine dissection)
• Have ≥ CTCAE Grade 2 eye diseases at screening, such as conjunctival mixed cellular inflammation, corneal ulcer.
• Have severe chronic or active infection requiring intravenous antibiotic treatment(s) within 2 weeks prior to the first dose, including but not limited to hospitalization due to infection complications, bacteremia, severe pneumonia or active tuberculosis.
• Notes:
• Subjects with topical fungal infection of the skin or nails are eligible for study enrollment.
• Subjects receiving prophylactic antibiotics (e.g., to prevent urinary tract infections or exacerbations of chronic obstructive pulmonary disease), except for the antibiotics prohibited per protocol, are eligible for study enrollment.
• Received solid organ or hematopoietic bone marrow/stem cell transplantation within 5 years prior to the screening.
• Received chemotherapy, targeted therapy or immunotherapy within 4 weeks prior to the first dose, except for fluorouracil or small molecule target therapy.
• Notes: Fluorouracil or small molecule target therapy received within five half-life or 2 weeks (whichever is longer) prior to the first dose is not allowed.
• Received anti-tumor Chinese herbal medicines or proprietary Chinese medicines within 2 weeks prior to the first dose.
• Received extensive prior radiotherapy to more than 30% of bone marrow reserves; or received Whole Brain Radiation Therapy (WBRT) within 4 weeks prior to the first dose; or received palliative radiotherapy for non-target lesions (e.g., bone radiotherapy for pain relief), including stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) within 2 weeks prior to the first dose.
• Have adverse reactions related to previous anti-tumor therapy that have not recovered to ≤ CTCAE Grade 1 or previous baseline at screening.
• Notes: Subjects with alopecia, or ≤ CTCAE Grade 2 peripheral neuropathy, or hypothyroidism stabilized by hormone replacement therapy, etc. are allowed for the enrollment.

Where it is running

• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States
• Indiana University Simon and Bren Simon Comprehensive Cancer Center — Indianapolis, Indiana, United States
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• Next Oncology — Irving, Texas, United States
• Huntsman Cancer Institute, University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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