A Phase I, First-In-Human, Multicenter, Open Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety and Efficacy of ABM-168 Administered Orally in Adult Patients with Advanced Solid Tumors

ABM Therapeutics Corporation6 sites in 1 country12 target enrollmentMarch 30, 2023

ConditionsAdvanced Solid Tumor RAS Mutation RAF Mutation NF1 Mutation

InterventionsABM-168

Overview

Phase: Phase 1
Intervention: ABM-168
Conditions: Advanced Solid Tumor
Sponsor: ABM Therapeutics Corporation
Enrollment: 12
Locations: 6
Primary Endpoint: Safety and tolerability-Respiratory Rate
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

This is a First-in-Human (FIH), open-label, multicenter, dose escalation and dose expansion, Phase I study of ABM-168, for the treatment of advanced solid tumors in adult patients. The study consists of two parts: Part A: Dose escalation. The starting dose of ABM-168 is 0.5 mq po qd, and dose escalation will be guided by a "3+3" design. ABM-168 will be administered once daily on a continuous schedule. Each treatment cycle consists of 28 days. Part B: Dose Expansion. Expansion will be conducted in the adult patients with advanced solid tumors that carry either RAS, RAF or NF-1 mutations. There are two cohorts for Dose Expansion: Patients will be enrolled into either Dose Expansion Cohort 1 (EX1) or Dose Expansion Cohort 2 (EX2). * Cohort EX1: Patients enrolled will have preferred indications (i.e., melanoma, colon cancer, lung cancer, and pancreatic carcinoma) who had confirmed RAS, RAF or NF-1 mutations and measurable lesion(s) at the beginning of the study. Patients with measurable brain lesions(s) which have metastasized are highly preferred. * Cohort EX2: Patients enrolled will have primary CNS (Central Nervous System tumors with confirmed RAS, RAF or NF-1 mutations. Dose limiting toxicity (DLT) will be evaluated and managed per the pre-defined DLT criteria and rules specified in the protocol. MTD (Maximum Tolerated Dose) and/or RP2D will be determined based on the totality of safety, clinical pharmacokinetics, and efficacy data from all evaluable patients enrolled and in treated in both dose escalation cohorts and dose expansion cohorts. The RP2D (recommended phase II dose) could be the MTD, or alternatively a dose recommended by the SMC (Safety Monitoring Committee) if no MTD is determined in the dose escalation and/or dose expansion.

Registry

clinicaltrials.gov

Start Date

March 30, 2023

End Date

June 30, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

ABM Therapeutics Corporation

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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 ≥
•≥ 3 months life expectancy

Exclusion Criteria

•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.

Arms & Interventions

Experimental Monotherapy Dose Escalation

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.

Intervention: ABM-168

Experimental Monotherapy Dose Expansion-1

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.

Intervention: ABM-168

Experimental Monotherapy Dose Expansion-2

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.

Intervention: ABM-168