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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04190628
Recruitment Status : Recruiting
First Posted : December 9, 2019
Last Update Posted : August 19, 2020
Sponsor:
Information provided by (Responsible Party):
ABM Therapeutics, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor BRAF V600 Mutation Drug: ABM-1310 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation arm and MTD/RP2D Dose Confirmation arm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, First-In-Human, Multicenter, Open-Label Study of ABM-1310, Administered Orally in Adult Patients With Advanced Solid Tumors
Actual Study Start Date : June 16, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Dose Escalation
A 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.
Drug: ABM-1310
Starting dose at 25 mg po bid. Dose formulations are 25 mg and 100 mg capsules.
Other Name: ABM1310

Experimental: MTD/RP2D Confirmation
Patients 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.
Drug: ABM-1310
Starting dose at 25 mg po bid. Dose formulations are 25 mg and 100 mg capsules.
Other Name: ABM1310




Primary Outcome Measures :
  1. 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) ]

Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to 30 days from treatment discontinuation ]
    Safety and tolerability of ABM-1310 as a single agent

  2. Number of participants with abnormal laboratory values [ Time Frame: Up to 30 days from treatment discontinuation ]
    Safety and tolerability of ABM-1310 as a single agent

  3. Area under the concentration time curve (AUC) [ Time Frame: Up to Day 1 of Cycle 2 (each cycle is 28 days) ]
    Pharmacokinetic (PK) profile of ABM-1310 as a single agent

  4. Maximum plasma concentration (Cmax) [ Time Frame: Up to Day 1 of Cycle 2 (each cycle is 28 days) ]
    Pharmacokinetic (PK) profile of ABM-1310 as a single agent

  5. Steady-state concentration (Css) [ Time Frame: Up to Day 1 of Cycle 2 (each cycle is 28 days) ]
    Pharmacokinetic (PK) profile of ABM-1310 as a single agent

  6. Time to maximum plasma concentration (Tmax) [ Time Frame: Up to Day 1 of Cycle 2 (each cycle is 28 days) ]
    Pharmacokinetic (PK) profile of ABM-1310 as a single agent

  7. Half-life (T1/2) [ Time Frame: Up to Day 1 of Cycle 2 (each cycle is 28 days) ]
    Pharmacokinetic (PK) profile of ABM-1310 as a single agent

  8. Objective Response Rate (ORR) [ Time Frame: Up to study discontinuation (an average of 1 year) ]
    Preliminary efficacy of ABM-1310 as a single agent

  9. Disease Control Rate (DCR) [ Time Frame: Up to study discontinuation (an average of 1 year) ]
    Preliminary efficacy of ABM-1310 as a single agent

  10. Duration of Response (DOR) [ Time Frame: Up to study discontinuation (an average of 1 year) ]
    Preliminary efficacy of ABM-1310 as a single agent


Other Outcome Measures:
  1. Exploratory preliminary efficacy in patients by types of BRAF V600 mutation [ Time Frame: Up to study discontinuation (an average of 1 year) ]
    Preliminary efficacy of ABM-1310 as a single agent

  2. Exploratory progression free survival (PFS) [ Time Frame: Up to study discontinuation (an average of 1 year) ]
    Preliminary efficacy of ABM-1310 as a single agent



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 stable brain metastasis or with active brain metastasis that are asymptomatic, or that are symptomatic but requiring a stable or decreasing dose of steroids for at least 2 weeks, are allowed for enrollment. (Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology- Friends of Cancer Research Brain Metastases Working Group 2017).
    • Active, symptomatic brain metastasis: patients with nerologic signs and symptoms may be 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. 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. ECOG performance status of 2 will be allowed in the RP2D Dose Confirmation Cohort.
  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 bilirubin <ULN for patients with total 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 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 FDA approved BRAF and MEK inhibitor treatment, whichever is shorter
  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 patietns who have not recovered from side effects of such therapy
  14. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04190628


Contacts
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Contact: Charles Zhao, M.D. 858-666-5491 czhao@abmtx.com

Locations
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United States, Michigan
Henry Ford Cancer Institute Recruiting
Detroit, Michigan, United States, 48202
Contact: Liping Zhu       Lzhu1@hfhs.org   
Principal Investigator: Ding Wang, M.D.         
United States, Nevada
Comprehensive Cancer Centers of Nevada (CCCN) Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Christine Zades       christine.zades@usoncology.com   
Principal Investigator: Fadi Braiteh, M.D.         
Sub-Investigator: Nicholas J Vogelzang, M.D.         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Rabia Khan       rkhan@mdanderson.org   
Principal Investigator: Sarina A. Piha-Paul, M.D.         
Sponsors and Collaborators
ABM Therapeutics, Inc.
Investigators
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Principal Investigator: Sarina A Piha-Paul, M.D. M.D. Anderson Cancer Center
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Responsible Party: ABM Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04190628    
Other Study ID Numbers: ABM1310X1101
First Posted: December 9, 2019    Key Record Dates
Last Update Posted: August 19, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ABM Therapeutics, Inc.:
Melanoma
Colorectal Cancer
Glioblastoma
Cholangiocarcinoma
Non-small Cell Lung Cancer
Thyroid Cancer
Ovarian Cancer
Additional relevant MeSH terms:
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Neoplasms