Clinical Trials /

Safety of ABM-1310 Monotherapy in Patients With Advanced Solid Tumors

NCT04190628

Description:

This is a Phase I, First-In-Human, open label, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of ABM-1310. A "3+3" design will be used to determine MTD and RP2D.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety of ABM-1310 Monotherapy in Patients With Advanced Solid Tumors
  • Official Title: A Phase I, First-In-Human, Multicenter, Open-Label Study of ABM-1310, Administered Orally in Adult Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ABM1310X1101
  • NCT ID: NCT04190628

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
ABM-1310ABM1310Dose Escalation

Purpose

This is a Phase I, First-In-Human, open label, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of ABM-1310. A "3+3" design will be used to determine MTD and RP2D.

Detailed Description

      This is a first-in-human, phase I clinical study with ABM-1310, an investigational, oral,
      small molecule B-Raf inhibitor in patients with documented BRAF V600 mutation and locally
      advanced or metastatic solid tumors such as melanoma, colorectal cancer, glioblastoma,
      cholangiocarcinoma, non-small cell lung cancer, thyroid cancer, or ovarian carcinoma who have
      no effective standard treatment options available. The primary objective of this study is to
      determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase II Dose (RP2D).

      The starting dose of ABM-1310 is 25 mg po bid, and dose escalation will be guided by a "3+3"
      design. ABM-1310 will be administered twice daily on a continuous schedule. Each treatment
      cycle consists of 28 days.

      Dose limiting toxicity (DLT) will be evaluated and managed per the pre-defined DLT criteria
      and rules specified in the protocol. MTD and/or RP2D will be confirmed in a dose confirmation
      cohort.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalA classic "3+3" design will be used to determine MTD and RP2D. Three to six patients per treatment cohort will be assigned to receive sequentially higher oral doses of ABM-1310 on a twice daily schedule (bid) for 28-day cycles, starting at a dose of 25 mg bid. Patients will receive twice daily oral doses of ABM-1310 until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.
  • ABM-1310
MTD/RP2D ConfirmationExperimentalPatients will receive twice daily oral doses of ABM-1310 in 28-day treatment cycles until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
  • ABM-1310

Eligibility 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 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 B-Raf V600 mutation
                  is required for enrollment.

               -  Patients with active brain metastasis are not eligible for enrollment

               -  Patients with asymptomatic or stable brain metastasis are allowed for enrollment
                  if there is strong scientific rationale for likelihood of benefit on the basis of
                  molecular pathways per PI's judgment and discussed with SMC (Modernizing Clinical
                  Trial Eligibility Criteria: Recommendations of the American Society of Clinical
                  Oncology-Friends of Cancer Research Brain Metastases Working Group 2017).

                    -  Stable brain metastasis is defined as patients are on a stable (unchanged)
                       dose of corticosteroids for more than one month, or patients are off
                       corticosteroid for at least 2 weeks. (Investigators are encouraged to
                       communicate with the medical monitor case by case for those
                       steroids-dependent patients with brain metastases.)

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

          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:

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

               2. Hemoglobin (Hgb) ≥ 9 g/dl

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

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

               5. Total bilirubin ≤ 1.5 x ULN, or direct bilirubin <ULN for patients with total
                  bilirubin levels >1.5 ULN

               6. 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

               1. A history of primary central nervous system tumors or

               2. Carcinomatous meningitis

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

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

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

               2. Congenital long QT syndrome

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

               4. Unstable angina pectoris ≤ 6 months prior to starting study drug

               5. Acute myocardial infarction ≤ 6 months prior to starting study drug

               6. Use of pacemaker

          8. Patients with

               1. Unresolved diarrhea ≥ CTCAE Grade 2, or

               2. Impairment of gastrointestinal (GI) function, or

               3. 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)

          9. 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

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

         11. Patients who have received chemotherapy, targeted therapy or immunotherapy ≤ 4 weeks
             (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not
             recovered from side effects of such therapy

         12. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field
             radiation for palliation ≤ 2 weeks prior to starting study drug or who have not
             recovered from side effects of such therapy

         13. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or
             who have not recovered from side effects of such therapy

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

         15. 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

         16. 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

         17. 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)

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

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

         20. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine Maximum Tolerated Dose (MTD) / Recommended Phase 2 Dose (RP2D)
Time Frame:End of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation (an average of 6 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:Up to 30 days from treatment discontinuation
Safety Issue:
Description:Safety and tolerability of ABM-1310 as a single agent
Measure:Number of participants with abnormal laboratory values
Time Frame:Up to 30 days from treatment discontinuation
Safety Issue:
Description:Safety and tolerability of ABM-1310 as a single agent
Measure:Area under the concentration time curve (AUC)
Time Frame:Up to Day 1 of Cycle 2 (each cycle is 28 days)
Safety Issue:
Description:Pharmacokinetic (PK) profile of ABM-1310 as a single agent
Measure:Maximum plasma concentration (Cmax)
Time Frame:Up to Day 1 of Cycle 2 (each cycle is 28 days)
Safety Issue:
Description:Pharmacokinetic (PK) profile of ABM-1310 as a single agent
Measure:Steady-state concentration (Css)
Time Frame:Up to Day 1 of Cycle 2 (each cycle is 28 days)
Safety Issue:
Description:Pharmacokinetic (PK) profile of ABM-1310 as a single agent
Measure:Time to maximum plasma concentration (Tmax)
Time Frame:Up to Day 1 of Cycle 2 (each cycle is 28 days)
Safety Issue:
Description:Pharmacokinetic (PK) profile of ABM-1310 as a single agent
Measure:Half-life (T1/2)
Time Frame:Up to Day 1 of Cycle 2 (each cycle is 28 days)
Safety Issue:
Description:Pharmacokinetic (PK) profile of ABM-1310 as a single agent
Measure:Objective Response Rate (ORR)
Time Frame:Up to study discontinuation (an average of 1 year)
Safety Issue:
Description:Preliminary efficacy of ABM-1310 as a single agent
Measure:Disease Control Rate (DCR)
Time Frame:Up to study discontinuation (an average of 1 year)
Safety Issue:
Description:Preliminary efficacy of ABM-1310 as a single agent
Measure:Duration of Response (DOR)
Time Frame:Up to study discontinuation (an average of 1 year)
Safety Issue:
Description:Preliminary efficacy of ABM-1310 as a single agent

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:ABM Therapeutics, Inc.

Trial Keywords

  • Melanoma
  • Colorectal Cancer
  • Glioblastoma
  • Cholangiocarcinoma
  • Non-small Cell Lung Cancer
  • Thyroid Cancer
  • Ovarian Cancer

Last Updated

December 4, 2019