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

NCT04190628 | Terminated Phase 1 FDA Drug

• 1 other identifier: ABM1310X1101
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 8

Brief 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, 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.

Conditions

Advanced Solid Tumor; BRAF V600 Mutation

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

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

• 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

  Up to study discontinuation (an average of 1 year)

• 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

  Up to study discontinuation (an average of 1 year)

Secondary Outcomes (13)

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

  Up to 30 days from treatment discontinuation

• Number of participants with abnormal laboratory values

  Up to 30 days from treatment discontinuation

• Area under the concentration time curve (AUC)

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

• Maximum plasma concentration (Cmax)

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

• Steady-state concentration (Css)

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

Other Outcomes (2)

• Exploratory preliminary efficacy in patients by types of BRAF V600 mutation

  Up to study discontinuation (an average of 1 year)

• Identification of major metabolite of ABM-1310 in patients who receive ABM-1310 monotherapy in Part C

  Up to study discontinuation (an average of 1 year)

Study Arms (6)

Monotherapy Dose Escalation

EXPERIMENTAL

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 continuously until disease progression, unacceptable toxicity, or a clinical observation satisfying another withdrawal criterion is met.

Drug: ABM-1310

Combination Therapy Dose Escalation

EXPERIMENTAL

A 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.

Drug: ABM-1310; Drug: Cobimetinib

Monotherapy Therapy Dose Expansion-1

EXPERIMENTAL

\- 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.

Drug: ABM-1310

Monotherapy Therapy Dose Expansion-2

EXPERIMENTAL

\- 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.

Drug: ABM-1310

Combination Therapy Dose Expansion-1

EXPERIMENTAL

\- 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.

Drug: ABM-1310; Drug: Cobimetinib

Combination Therapy Dose Expansion-2

EXPERIMENTAL

\- 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.

Drug: ABM-1310; Drug: Cobimetinib

Interventions

ABM-1310 DRUG

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.

Also known as: ABM1310

Combination Therapy Dose Escalation; Combination Therapy Dose Expansion-1; Combination Therapy Dose Expansion-2; Monotherapy Dose Escalation; Monotherapy Therapy Dose Expansion-1; Monotherapy Therapy Dose Expansion-2

Cobimetinib DRUG

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.

Also known as: Cotellic®

Combination Therapy Dose Escalation; Combination Therapy Dose Expansion-1; Combination Therapy Dose Expansion-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• ABM Therapeutics Corporation: lead

Study Sites (8)

University of California- San Francisco

San Francisco, California, 94158, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Miami Hospital Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Robert H. Lurie Comprehensive Cancer Center (Northwestern University)

Chicago, Illinois, 60611, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

UTHealth Science Center Houston Department of Neurosurgery

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Melanoma; Colorectal Neoplasms; Glioblastoma; Cholangiocarcinoma; Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Ovarian Neoplasms

Interventions

cobimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders

Study Officials

• Sarina A Piha-Paul, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 9, 2019
• Study Start: June 16, 2020
• Primary Completion: April 5, 2024
• Study Completion: April 5, 2024
• Last Updated: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)