Safety and Tolerability of ABM-1310 in Patients With Advanced Solid Tumors

Not Recruiting

Trial ID: NCT04190628


This is a Phase I, First-In-Human, open label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer activity of ABM-1310 in adult patients with locally advanced or metastatic solid tumors who have no effective standard treatment options available, as monotherapy in patients with documented BRAF V600 mutation, or in combination with cobimetinib (Cotellic®) in adult patients who have documented BRAF mutation and progressive disease or intolerance to at least one prior line of systemic therapy.

Official Title

A Phase I, First-In-Human, Multicenter, Open-Label Dose Escalation and Dose Expansion Study of ABM-1310, as a Monotherapy and a Combination Therapy, Administered Orally in Adult Patients With Advanced Solid Tumors Harboring BRAF Mutations

Stanford Investigator(s)

Seema Nagpal, MD
Seema Nagpal, MD

Clinical Professor, Neurology & Neurological Sciences Clinical Professor (By courtesy), Neurosurgery


Inclusion Criteria:

   1. Male and female subjects age 18 years and older who are able to sign informed consent
   and to comply with the protocol

   2. Patients with histologically or cytologically-documented, locally advanced, or
   metastatic solid tumor malignancy that has either (a) progressed on at least one line
   of prior standard systemic therapy, (b) for which no standard therapy exists, or (c)
   standard therapy is not considered appropriate by the patient or treating physician.
   There is no limit to the number of prior treatment regimens

      - Part A: Patients with advanced or metastatic solid tumors with documentation of
      positive BRAF V600E mutation, or any other BRAF V600 mutation is required for

      - Part B: Patients with advanced or metastatic solid tumors with documentation of
      any BRAF mutation.

      - Part C:

         1. C-1: Patients with primary central nervous system (CNS) tumors and
         documentation of positive BRAF V600 mutation

         2. C-2: Patients with advanced or metastatic solid tumors and documentation of
         positive BRAF V600 mutation excluding primary CNS tumor

         3. C-3: Patients with advanced or metastatic solid tumors and documentation of
         positive BRAF mutation including primary CNS tumors but excluding melanoma
         with brain metastasis

         4. C-4: Patients with melanoma with brain metastasis and documentation of
         positive BRAF mutation

   Patients with active or stable brain metastasis that are asymptomatic, or that are
   symptomatic treated with a total daily dose of no more than 4 mg of dexamethasone (or
   equivalent) that is stable or tapering for at least 2 weeks prior to first treatment
   are eligible for enrollment. Patients with neurologic signs and symptoms who are not
   being treated with steroids are eligible and should have no experience of seizure
   within 2 weeks prior to first treatment.

   3. Must have at least one measurable lesion as defined by RECIST V1.1 criteria for solid
   tumors or the RANO criteria for primary CNS tumors, such as gliomas.

      - For solid tumor with Brain Metastases:

      - Measurable brain lesions that are 0.5 - 3 cm in longest diameter as defined by
      the modified RECIST V1.1 criteria are allowed.

      - Brain lesion size > 3 cm is not eligible.

   4. ECOG performance status of 0 or 1 or Karnofsky performance status of ≥ 70

   5. Adequate organ function confirmed at screening and within 28 days of initiating
   treatment, as evidenced by:

      - Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/L

      - Hemoglobin (Hgb) ≥ 9 g/dl

      - Platelets (Plt) ≥ 100 x 10^9/L

      - AST/ALT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases
      are present

      - Total bilirubin ≤ 1.5 x ULN, or direct bilirubin
      bilirubin levels >1.5 ULN

      - Serum creatinine <1.5 x ULN or measured or calculated (per institutional
      standard) creatinine clearance of > 60 mL/min.

   6. Negative pregnancy test within 72 hours before starting study treatment in all
   pre-menopausal women and women <12 months after the onset of menopause

   7. Male and female subjects must agree to take sufficient contraceptive methods to avoid
   pregnancy before first dose of study treatment, during the study, and for at least 3
   months after ceasing study treatment

Exclusion Criteria:

   1. Women who are pregnant or breast-feeding

   2. Women of child-bearing potential (WOCBP) who does not use adequate birth control

   3. Patients with any hematologic malignancy. This includes leukemia, lymphoma, and
   multiple myeloma

   4. Have a second primary malignancy that, in the judgment of the investigator, may affect
   the interpretation of results

   5. Patients with carcinomatous meningitis (leptomeningeal disease (LMD))

   6. Patients with history of stroke ≤ 6 months prior to starting study drug

   7. Patients who have had an experience of seizure within 14 days prior to first treatment

   8. Impaired cardiac function or clinically significant cardiac diseases, including but
   not limited to any of the following:

      - Left Ventricular Ejection Fraction (LVEF) < 45% as determined by MUGA scan or

      - Congenital long QT syndrome

      - QTcF ≥ 450 msec (mean) on screening (Triplicate 12-Lead ECG)

      - Unstable angina pectoris ≤ 6 months prior to starting study drug

      - Acute myocardial infarction ≤ 6 months prior to starting study drug

      - Use of pacemaker

   9. Patients with

      - Unresolved diarrhea ≥ CTCAE Grade 2, or

      - Impairment of gastrointestinal (GI) function, or

      - GI disease or conditions that may significantly alter the absorption of ABM-1310
      (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
      malabsorption syndrome, or small bowel resection)

10. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
   uncontrolled hypertriglyceridemia [triglycerides >500 mg/dL], active or uncontrolled
   infection) that could cause unacceptable safety risks or compromise compliance with
   the protocol

11. Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone
   marrow/stem cell transplantation within 5 years

12. Patients who have received chemotherapy, targeted therapy or immunotherapy ≤ 4 weeks
   prior to starting study drug or who have not recovered from side effects of such
   therapy, except:

      - ≤ 6 weeks for nitrosourea or mitomycin-C

      - ≤ 5 half-lives or 2 weeks for small molecule inhibitor treatment, whichever is

13. Patients who have received wide field radiotherapy ≤ 4 weeks, limited field radiation
   for palliation ≤ 2 weeks, prior whole-brain radiotherapy (WBRT) ≤ 4 weeks or
   stereotactic radiosurgery (SRS) ≤ 2 weeks (one week for patients with primary CNS
   tumor such as GBM or with brain metastasis) prior to starting study drug or patients
   who have not recovered from side effects of such therapy

14. Patients who have undergone major surgery ≤ 4 weeks in general prior to starting study
   drug or who have not recovered from side effects of such therapy. However, a minimum
   of 2 weeks recovery time from major surgery prior to starting study drug is acceptable
   if in investigator's opinion the patient has recovered from surgery.

15. Patients who are currently receiving treatment with therapeutic doses of warfarin
   sodium or any other coumarin-derivative anticoagulants

16. Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study
   drug or who have not recovered from the side effects of such treatment. Therapeutic
   doses of corticosteroids up to 4 mg/day of dexamethasone, or equivalent are allowed.
   Note: Patients that are taking replacement doses of steroids are eligible

17. Patients who are currently receiving treatment with medication that has known risk to
   prolong the QT interval, and the treatment cannot either be discontinued or switched
   to a different medication prior to starting study drug

18. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
   mandatory; patients with well controlled HIV might be enrolled per investigator's

19. Known history of active infection with Hepatitis B (e.g., HBsAg reactive), or
   Hepatitis C (e.g., S RNA (qualitative) is detected)

20. History of alcohol or drug abuse ≤ 3 months prior to first dose

21. Has a history or current evidence of any condition, therapy, or laboratory abnormality
   that, in the opinion of the investigator, might confound the results of the trial,
   interfere with the patient's participation and compliance in the trial


drug: ABM-1310

drug: Cobimetinib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Priya Yerraballa

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