Safety and Effectiveness of ABM-168 in Adults with Advanced Solid Tumors.

NCT05831995 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ABM168X1101
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase 1, First-in-Human (FIH), open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ABM-168 in adult patients with RAS or RAF or NF-1 mutated advanced solid tumors as ABM-168 may have a significant effect in inhibiting cell growth.

Conditions

Advanced Solid Tumor; RAS Mutation; RAF Mutation; NF1 Mutation

Keywords

Melanoma; Glioblastoma; Colorectal cancer; Lung cancer; Pancreatic cancer; Metastatic brain tumors; Primary CNS tumors; All Solid Tumors

Outcome Measures

Primary Outcomes (15)

• Determine Dose Limiting Toxicity (DLT) and/or Recommended Phase 2 dose (RP2D)

  Dose limiting toxicities (DLT) which defines the MTD/RP2D

  Day 28 after last dosing.

• Safety and tolerability-Incident Rate.

  Safety and tolerability of ABM-168 monotherapy as determined by incident rate.

  Day 28 after last dosing.

• Safety and tolerability, severity per Common Toxicity Criteria for Adverse Events (CTCAE v5.0)

  Safety and tolerability of ABM-168 monotherapy as determined by severity. Adverse events will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. For consistency, Version 5.0 will be used throughout the trial regardless of any subsequent versions of the CTCAE criteria that may become available. If CTCAE grading does not exist for a specific adverse event, the severity should be assessed based on the general guidelines outlined in CTCAE v5.0.

  Day 28 after last dosing.

• Safety and tolerability-AE causality.

  Safety and tolerability of ABM-168 monotherapy as determined by causality of adverse events (AEs).

  Day 28 after last dosing.

• Safety and tolerability-Lab abnormalities.

  Safety and tolerability of ABM-168 monotherapy as determined by clinically significant abnormalities in clinical laboratory testing.

  Day 28 after last dosing.

• Safety and tolerability-Body Temperature.

  Safety and tolerability of ABM-168 monotherapy as determined by body temperature changes from base-line in Fahrenheit.

  Day 28 after last dosing.

• Safety and tolerability-Heart Rate

  Safety and tolerability of ABM-168 monotherapy as determined by heart rate changes from base-line in BPM (beats per minute).

  Day 28 after last dosing.

• Safety and tolerability-Pulse Rate

  Safety and tolerability of ABM-168 monotherapy as determined by pulse rate changes from base-line in BPM (beats per minute).

  Day 28 after last dosing.

• Safety and tolerability-Respiratory Rate

  Safety and tolerability of ABM-168 monotherapy as determined by respiratory rate changes from base-line in breaths per minute.

  Day 28 after last dosing.

• Safety and tolerability-Systolic Blood Pressure

  Safety and tolerability of ABM-168 monotherapy as determined by blood pressure changes from base-line in systolic blood pressure (measured in mmHg).

  Day 28 after last dosing.

• Safety and tolerability-Diastolic Blood Pressure

  Safety and tolerability of ABM-168 monotherapy as determined by blood pressure changes from base-line in diastolic blood pressure (measured in mmHg).

  Day 28 after last dosing.

• Safety and tolerability-Ocular side effects.

  Safety and tolerability of ABM-168 monotherapy as determined by ophthalmology assessment.

  Day 28 after last dosing.

• Safety and tolerability-ECG parameters.

  Safety and tolerability of ABM-168 monotherapy as determined by ECGs (QT interval).

  Day 28 after last dosing.

• Safety and tolerability-ECOG performance

  Safety and tolerability of ABM-168 monotherapy as determined by ECOG scores (0-Fully active; - 5-Dead).

  Day 28 after last dosing.

• Safety and tolerability-Karnofsky performance.

  Safety and tolerability of ABM-168 monotherapy as determined by Karnofsky performance scores - 70 (able to care for self and live at home) - 100 (able to carry on normal activity).

  Day 28 after last dosing.

Study Arms (3)

Experimental Monotherapy Dose Escalation

EXPERIMENTAL

A classic "3+3" design will be used to explore the maximum tolerated dose (MTD) and to determine the recommended phase II dose (RP2D). Three to four patients will be enrolled to ensure at least 3 evaluable patients for DLT (Dose Limiting Toxicity). ABM-168 monotherapy will be conducted in seven provisional dose levels starting at 0.5mg oral administration per day and up to and including 12mg oral administration. Each treatment cycle is 28-days. DLT will be evaluated in the first 28-day cycle. Patients will receive daily doses of ABM-168 until disease progression; intolerable toxicity; withdrawal consent; or other clinical observation is met.

Drug: ABM-168

Experimental Monotherapy Dose Expansion-1

EXPERIMENTAL

Expansion will be conducted in the adult patients with advanced solid tumors that carry either RAS, RAF or NF-1 mutations. Cohort EX1 will enroll the patients with preferred indications (i.e., melanoma, colon cancer, lung cancer, and pancreatic carcinoma) who had confirmed RAS, RAF or NF-1 mutations and measurable target lesion(s) at baseline. Patients with measurable brain metastases lesion(s) at baseline are highly preferred. Up to 15 evaluable patients will be enrolled for each into each preferred indication. Other indication(s) that show confirmed response, complete response (CR) or partial response (PR) in at least one subject in the dose escalation study will facilitate the preferred indication(s) for Cohort EX1 enrollment as well.

Drug: ABM-168

Experimental Monotherapy Dose Expansion-2

EXPERIMENTAL

Expansion will be conducted in the adult patients with advanced solid tumors that carry either RAS, RAF or NF-1 mutations. Cohort EX2 will enroll the patients who had primary CNS tumors with confirmed RAS, RAF or NF-1 mutations at baseline. Up to 30 evaluable patients will be enrolled.

Drug: ABM-168

Interventions

ABM-168 DRUG

Dosage: 0.5 mg; 2 mg; 6 mg; once daily by oral administration

Experimental Monotherapy Dose Escalation; Experimental Monotherapy Dose Expansion-1; Experimental Monotherapy 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 comply with the protocol
• Patients with histologically or cytologically documented, locally advanced, or metastatic solid tumor malignancy that has either:
• failed prior standard therapy; or
• exhausted all existing standard therapy; or
• standard therapy is not considered appropriate per subject and/or investigator. No limitation on the lines of previous standard therapy received.
• Patients with asymptomatic or symptomatic but stable brain metastases or CNS primary malignancies who meet following criteria specifically:
• Asymptomatic, brain metastases or primary CNS tumors;
• Stable symptomatic brain metastases or CNS primary tumors not requiring steroids treatment or receiving steroids treatment (dexamethasone or equivalent) with total daily dosage no more than 4 mg, with a stable or reduced dosage of steroids within 2 weeks prior to the planned first dose
• ECOG performance score of 0 or 1, or Karnofsky performance score of ≥ 70.
• ≥ 3 months life expectancy
• Receiving no blood transfusions or granulocyte colony-stimulating factor (G-CSF) or other hematopoietic stimulating factors within 2 weeks prior to the planned first dosing. Adequate organ function confirmed at screening as evidenced by:
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L
• Hemoglobin (Hgb) ≥ 90 g/dL
• Platelets (Plt) ≥ 75 ×10\^9/L
• AST/ALT ≤ 2.5 × Upper Limit of Normal (ULN) or ≤ 5.0 × ULN if liver metastases are present

You may not qualify if:

• Women who are pregnant or breast-feeding.
• Have leptomeningeal disease (LMD).
• Have a history of stroke within 6 months prior to the first dose.
• Have impaired cardiac function or clinically significant cardiovascular disease(s) including but not limited to any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by cardiac ultrasound.
• Congenital long QT syndrome.
• Grade 2 type II AV block or grade 3 AV block.
• Unstable angina within 6 months prior to the first dose.
• Acute myocardial infarction within 6 months prior to the first dose.
• ≥ Class III heart failure per New York Heart Association (NYHA) functional classification within 6 months prior to the first dose.
• ≥ CTCAE Grade 2 ventricular arrhythmia within 6 months prior to study initiation.
• Have uncontrolled hypertension at screening, with systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg after receiving anti-hypertension treatment.
• Have unresolved ≥ CTCAE Grade 2 diarrhea at the time of the first dose; or have gastrointestinal impairment conditions or diseases that significantly alter ABM-168 absorption at screening per investigator (e.g., ulcerative disease, poorly controlled nausea, vomiting, malabsorption syndrome, or small intestine dissection)
• Have ≥ CTCAE Grade 2 eye diseases at screening, such as conjunctival mixed cellular inflammation, corneal ulcer.
• Have severe chronic or active infection requiring intravenous antibiotic treatment(s) within 2 weeks prior to the first dose, including but not limited to hospitalization due to infection complications, bacteremia, severe pneumonia or active tuberculosis.

Sponsors & Collaborators

• ABM Therapeutics Corporation: lead

Study Sites (6)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Indiana University Simon and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology

Irving, Texas, 75039, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Melanoma; Glioblastoma; Colorectal Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Brain Neoplasms

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; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

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 two parts: * Part A: ABM-168 Dose Escalation and DLT Dose Confirmation * Part B: Dose Expansion (ABM-168 Monotherapy)

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: April 27, 2023
• Study Start: March 30, 2023
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)