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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.

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.

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.

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

ABM-168

Katie Zhou

Michael Wong

Katy Tsai, M.D.

Mateusz Opyrchal, M.D.

Suzanne Bailey

Taryn Bollaro

Sanjay Goel, MD

Rabia Khan

Sarina A. Piha-Paul, M.D.

Shiraj Sen, MD, PhD

Ignacio Garrido-Laguna, M.D.

Jamie White

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.

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.

Study consists of two parts:

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

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Effectiveness of ABM-168 in Adults With Advanced Solid Tumors.	NCT05831995	Advanced Solid ... RAS Mutation RAF Mutation NF1 Mutation	ABM-168	18 Years -	ABM Therapeutics Corporation
Safety and Effectiveness of ABM-168 in Adults With Advanced Solid Tumors.	NCT05831995	Advanced Solid ... RAS Mutation RAF Mutation NF1 Mutation	ABM-168	18 Years -	ABM Therapeutics Corporation

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