Safety of ABM-1310 in Patients With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase I, First-In-Human, open label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer activity of ABM-1310 in adult patients with documented BRAF V600 mutation and locally advanced or metastatic solid tumors who have no effective standard treatment options available, as monotherapy in Part A, or in combination with cobimetinib (Cotellic®) in Part B in adult patients who also have documented progressive disease or intolerance to previous combination treatment of BRAF and MEK inhibitors. A "3+3" design will be used to determine MTD and RP2D.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ABM Therapeutics, Inc.

Criteria

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) failed prior standard 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.

• Documentation of positive BRAF V600E mutation, or any other BRAF V600 mutation is required for enrollment.

• Patients with stable brain metastasis that are asymptomatic, or that are symptomatic but on a stable low dose up to 4 mg of dexamethasone (or equivalent) per day of corticosteroids for at least 2 weeks prior to screening, are eligible for enrollment. (Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology- Friends of Cancer Research Brain Metastases Working Group 2017).

• Part B: patients with documented progressive disease on or intolerance to previous combination treatment of BRAF and MEK inhibitors.

3. Must have at least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors

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

• Brain lesion size > 3 cm is not eligible.

4. ECOG performance status of 0 or 1

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 bilirubinbilirubin 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 60 days 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 (any form), 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 ECHO

• 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 longer

13. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks, prior whole-brain radiotherapy (WBRT) ≤ 4 weeks or stereotactic radiosurgery (SRS) ≤ 2 weeks 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 is 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 discretion)

19. Known history of active infection with Hepatitis B (e.g., HBsAg reactive), or Hepatitis C (e.g., HCV 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