The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RAS(ON) inhibitors in combination with ivonescimab in adults with advanced or metastatic solid tumors with a RAS mutation.
This is an open-label, multicenter, Phase 1/2 study of RAS(ON) inhibitors in combination with ivonescimab with or without other anti-cancer agents in adults with advanced or metastatic solid tumors with a RAS mutation to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: Arm A:daraxonrasib in combination with ivonescimab; Arm B: elironrasib in combination with ivonescimab; and Arm C: zoldonrasib in combination with ivonescimab. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Part 1 dose exploration will explore the safety and tolerability of individual RAS(ON) inhibitors in combination with ivonescimab. Part 2 dose expansion will explore the safety, tolerability, and antitumor activity of the individual RAS(ON) inhibitors with ivonescimab +/- anti-cancer therapies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
370
oral tablets
oral tablets
oral tablets
IV infusion
IV infusion
IV infusion
IV infusion
oral tablets
NEXT Virginia
Fairfax, Virginia, United States
RECRUITINGNumber of patients with adverse events (AEs)
Number of patients with AEs as assessed by CTCAE v5.
Time frame: Up to approximately 4 years
Changes in vital signs
Number of patients with changes in vital signs.
Time frame: Up to approximately 4 years
Changes in clinical laboratory test values
Number of patients with changes in clinical laboratory test values.
Time frame: Up to approximately 4 years
Dose Limiting Toxicities
Number of patients with dose limiting toxicities
Time frame: 28 days
Concentration of RAS(ON) inhibitors and ivonescimab
Trough and peak blood concentrations of RAS(ON) inhibitors and ivonescimab over time as applicable.
Time frame: Up to Cycle 6 Day 1 (each cycle is 21 days)
Objective Response Rate (ORR)
ORR per response evaluation criteria in solid tumors (RECIST) v1.1
Time frame: Up to approximately 4 years
Duration of Response (DOR)
DOR per RECIST v1.1
Time frame: Up to approximately 4 years
Disease Control Rate (DCR)
DCR per RECIST v1.1
Time frame: Up to approximately 4 years
Time to response (TTR)
TTR per RECIST v1.1
Time frame: Up to approximately 4 years
Progression free survival (PFS)
PFS per RECIST v1.1
Time frame: Up to approximately 4 years
Anti-drug Antibody (ADA) of ivonescimab
Number and percentage of patients with anti-ivonescimab antibody
Time frame: Up to approximately 4 years
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