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Advanced Solid TumorPhase 1NCT04190628

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

A Phase 1 study testing ABM-1310 and Cobimetinib in people with Advanced Solid Tumor and BRAF V600 Mutation, run by ABM Therapeutics Corporation at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor, BRAF V600 Mutation
What is being tested?
ABM-1310 and Cobimetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
8 sitesUnited States
Study dates
16 Jun 2020to 5 Apr 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female subjects age 18 years and older who are able to sign informed consent and to comply with the protocol
  • 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 enrollment
  • Part B: Patients with advanced or metastatic solid tumors with documentation of any BRAF mutation.
  • Part C:
  • C-1: Patients with primary central nervous system (CNS) tumors and documentation of positive BRAF V600 mutation
Show all 24Show fewer
  • C-2: Patients with advanced or metastatic solid tumors and documentation of positive BRAF V600 mutation excluding primary CNS tumor
  • 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
  • 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.
  • 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.
  • ECOG performance status of 0 or 1 or Karnofsky performance status of ≥ 70
  • 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.
  • Negative pregnancy test within 72 hours before starting study treatment in all pre-menopausal women and women <12 months after the onset of menopause
  • 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

Who cannot join

  • Women who are pregnant or breast-feeding
  • Women of child-bearing potential (WOCBP) who does not use adequate birth control
  • Patients with any hematologic malignancy. This includes leukemia, lymphoma, and multiple myeloma
  • Have a second primary malignancy that, in the judgment of the investigator, may affect the interpretation of results
  • Patients with carcinomatous meningitis (leptomeningeal disease (LMD))
  • Patients with history of stroke ≤ 6 months prior to starting study drug
Show all 32Show fewer
  • Patients who have had an experience of seizure within 14 days prior to first treatment
  • 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
  • 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)
  • 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
  • Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years
  • 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
  • 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
  • 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.
  • Patients who are currently receiving treatment with therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulants
  • 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
  • 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
  • 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)
  • Known history of active infection with Hepatitis B (e.g., HBsAg reactive), or Hepatitis C (e.g., S RNA (qualitative) is detected)
  • History of alcohol or drug abuse ≤ 3 months prior to first dose
  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Robert H. Lurie Comprehensive Cancer Center (Northwestern University)

    Chicago, Illinois, 60611

  • Henry Ford Cancer Institute

    Detroit, Michigan, 48202

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • UTHealth Science Center Houston Department of Neurosurgery

    Houston, Texas, 77030

  • University of Miami Hospital Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Columbia University Medical Center

    New York, New York, 10032

  • University of California- San Francisco

    San Francisco, California, 94158

  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

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

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.

Read the detailed description

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. The primary objectives of this study are to determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase II Dose (RP2D) of both single agent and combination treatment and to assess the safety and tolerability of ABM-1310 as a monotherapy and in combination.

Study consists of three Parts:

Part A: 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.

Part B: The starting dose of ABM-1310 will be a dose below the MTD that has been demonstrated to be safe in Part A Monotherapy. A classic "3+3" design will guide the dose escalation. At each dose level, ABM-1310 will be administered in combination with 60 mg cobimetinib (Cotellic ®) once daily (qd) for the first 21 days of each 28-day treatment cycle.

Part C:

  • In C-1 (Monotherapy - Primary CNS Tumors) and C-2 (Monotherapy - Advanced or Metastatic solid tumors excluding Primary CNS tumors with or without Brain Metastasis), continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part A until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.
  • In C-3 (Combination therapy - Advanced/Metastatic Solid Tumors including Primary CNS Tumors but excluding Melanoma with Brain Metastsis) and C-4 (Combination therapy - Melanoma with Brain Metastasis), continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part B, in combination with cobimetinib (Cotellic®) 60 mg administered the first 21 days of each 28-day treatment cycle until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.

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.

Being tested
ABM-1310, Cobimetinib
Keywords
Melanoma, Colorectal Cancer, Glioblastoma, Cholangiocarcinoma, Non-small Cell Lung Cancer, Thyroid Cancer, Ovarian Cancer
Medical subject headings
Melanoma, Colorectal Neoplasms, Glioblastoma, Cholangiocarcinoma, Carcinoma, Non-Small-Cell Lung, Thyroid Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABM-1310Drug

    Also called ABM1310

    Part A: Starting dose at 25 mg by mouth twice daily.

    Part B: Starting dose at a dose below the MTD( Maximum Tolerated Dose) that has been demonstrated to be safe in Part A.

    Part C-1 and C-2: Continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part A until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.

    Part C-3 and C-4: Continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part B until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.

  • CobimetinibDrug

    Also called Cotellic®

    Part B: orally administered once daily.

    Part C-3 and C-4: Continuous once daily oral dose from Part B, administered the first 21 days of each 28-day treatment cycle until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.

    Dose formulation is 60 mg capsules.

Study groups in NCT04190628
Study groupRoleWhat they receive
Monotherapy 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 continuously until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.
Receives: Drug: ABM-1310
Combination Therapy Dose EscalationExperimentalA classic "3+3" design will guide the dose escalation in Part B. At each dose level, ABM-1310 will be administered in combination with cobimetinib (Cotellic ®) once daily (qd) for the first 21 days of each 28-day treatment cycle. The starting dose of ABM-1310 will be a dose below the MTD that has been demonstrated to be safe in Part A Monotherapy.
Receives: Drug: ABM-1310; Drug: Cobimetinib
Monotherapy Therapy Dose Expansion-1Experimental- In C-1(Monotherapy - Primary CNS Tumors), continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part A until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.
Receives: Drug: ABM-1310
Monotherapy Therapy Dose Expansion-2Experimental- In C-2 (Monotherapy - Advanced or Metastatic Solid Tumors excluding Primary CNS Tumor with or without Brain Metastasis), continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part A until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.
Receives: Drug: ABM-1310
Combination Therapy Dose Expansion-1Experimental- In C-3 (Combination therapy - Advanced/Metastatic Solid Tumors including Primary CNS tumors but excluding Melanoma with Brain metastasis), continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part B, in combination with cobimetinib (Cotellic®) 60 mg administered the first 21 days of each 28-day treatment cycle until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.
Receives: Drug: ABM-1310; Drug: Cobimetinib
Combination Therapy Dose Expansion-2Experimental- In C-4 (Combination therapy - Melanoma with Brain Metastasis), continuous twice daily oral doses of ABM-1310 at the recommended phase 2 dose (RP2D) from Part B, in combination with cobimetinib (Cotellic®) 60 mg administered the first 21 days of each 28-day treatment cycle until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.
Receives: Drug: ABM-1310; Drug: Cobimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

    Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) as a monotherapy and in combination therapy in Part A and Part B

    Measured: End of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation (an average of 6 months)

  2. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Safety and tolerability of ABM-1310 as a monotherapy and in combination therapy at Part A and Part B's Recommended Phase 2 dose (RP2D) in Part C

    Measured: Up to study discontinuation (an average of 1 year)

  3. Number of participants with abnormal laboratory values

    Safety and tolerability of ABM-1310 as a monotherapy and in combination therapy at Part A and Part B's Recommended Phase 2 Dose (RP2D) in Part C

    Measured: Up to study discontinuation (an average of 1 year)

Secondary outcomes (13)

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Safety and tolerability of ABM-1310 as a single agent and in combination therapy in Part A and Part B

    Measured: Up to 30 days from treatment discontinuation

  2. Number of participants with abnormal laboratory values

    Safety and tolerability of ABM-1310 as a single agent and in combination therapy in Part A and Part B

    Measured: Up to 30 days from treatment discontinuation

  3. Area under the concentration time curve (AUC)

    Pharmacokinetic (PK) profile of ABM-1310 as a single agent and in combination therapy

    Measured: Up to Day 1 of Cycle 2 (each cycle is 28 days)

  4. Maximum plasma concentration (Cmax)

    Pharmacokinetic (PK) profile of ABM-1310 as a single agent and in combination therapy

    Measured: Up to Day 1 of Cycle 2 (each cycle is 28 days)

  5. Steady-state concentration (Css)

    Pharmacokinetic (PK) profile of ABM-1310 as a single agent and in combination therapy

    Measured: Up to Day 1 of Cycle 2 (each cycle is 28 days)

  6. Time to maximum plasma concentration (Tmax)

    Pharmacokinetic (PK) profile of ABM-1310 as a single agent and in combination therapy

    Measured: Up to Day 1 of Cycle 2 (each cycle is 28 days)

  7. Half-life (T1/2)

    Pharmacokinetic (PK) profile of ABM-1310 as a single agent and in combination therapy

    Measured: Up to Day 1 of Cycle 2 (each cycle is 28 days)

  8. Objective Response Rate (ORR)

    Preliminary efficacy of ABM-1310 as a single agent and in combination therapy

    Measured: Up to study discontinuation (an average of 1 year)

  9. Disease Control Rate (DCR)

    Preliminary efficacy of ABM-1310 as a single agent and in combination therapy

    Measured: Up to study discontinuation (an average of 1 year)

  10. Duration of Response (DOR)

    Preliminary efficacy of ABM-1310 as a single agent and in combination therapy

    Measured: Up to study discontinuation (an average of 1 year)

  11. Progression free survival (PFS)

    Preliminary efficacy of ABM-1310 as a single agent and in combination therapy

    Measured: Up to study discontinuation (an average of 1 year)

  12. Overall Survival (OS)

    Preliminary efficacy of ABM-1310 as a single agent and in combination therapy

    Measured: Up to study discontinuation (an average of 1 year)

  13. Time to Response (TTR)

    Preliminary efficacy of ABM-1310 as a single agent and in combination therapy

    Measured: Up to study discontinuation (an average of 1 year)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2019
  2. Study start16 Jun 2020
  3. Primary completion5 Apr 2024
  4. Study completion5 Apr 2024

Why it stopped: Not related to safety concerns or lack of efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Study consists of Three Parts: Part A: ABM-1310 Dose Escalation and MTD/RP2D Dose Confirmation Part B: Combination agent (ABM-1310 and cobimetinib (Cotellic®)) Dose Escalation and MTD/RP2D Dose Confirmation Part C: Dose Expansion (ABM-1310 Monotherapy/Combination Therapy)
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04190628
Sponsor's protocol ID
ABM1310X1101
Status last verified
May 2024
First submitted
3 Dec 2019
Last updated
21 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABM-1310 and Cobimetinib in people with Advanced Solid Tumor and BRAF V600 Mutation, run by ABM Therapeutics Corporation at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Not related to safety concerns or lack of efficacy). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) and/or 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04190628.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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