Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Daraxonrasib, Elironrasib, Zoldonrasib, Ivonescimab.
- Who it may be relevant to
- Registry conditions: Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer (NSCLC), NSCLC. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Phase 1/2 Open-Label, Multicenter Study of RAS(ON) Inhibitors in Combination With Ivonescimab With or Without Other Anti-Cancer Agents in Patients With Solid Tumors
Overview
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.
Detailed description
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.
Interventions
- Drug Daraxonrasib
oral tablets - Drug Elironrasib
oral tablets - Drug Zoldonrasib
oral tablets - Drug Ivonescimab
IV infusion - Drug Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)
IV infusion - Drug cetuximab (Cohort C2 Only)
IV infusion - Drug Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)
IV infusion - Drug Daraxonrasib (Cohort B1 only)
oral tablets
Primary outcome measures
- Number of patients with adverse events (AEs) [Time frame: Up to approximately 4 years]
- Changes in vital signs [Time frame: Up to approximately 4 years]
- Changes in clinical laboratory test values [Time frame: Up to approximately 4 years]
- Dose Limiting Toxicities [Time frame: 28 days]
Secondary outcome measures (7)
- Concentration of RAS(ON) inhibitors and ivonescimab [Time frame: Up to Cycle 6 Day 1 (each cycle is 21 days)]
- Objective Response Rate (ORR) [Time frame: Up to approximately 4 years]
- Duration of Response (DOR) [Time frame: Up to approximately 4 years]
- Disease Control Rate (DCR) [Time frame: Up to approximately 4 years]
- Time to response (TTR) [Time frame: Up to approximately 4 years]
- Progression free survival (PFS) [Time frame: Up to approximately 4 years]
- Anti-drug Antibody (ADA) of ivonescimab [Time frame: Up to approximately 4 years]
Eligibility criteria
Inclusion criteria
- At least 18 years old and has provided informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically confirmed, locally advanced or metastatic solid tumor malignancy with documented RAS mutation in KRAS, HRAS, or NRAS.
- Received and progressed or been intolerant to prior standard therapy (Part 1 Dose Exploration).
- Non-squamous NSCLC without a treatable driver mutation in other oncogenes that has not received prior systemic treatment (Arms A \& B for Part 2 Dose Expansion).
- Solid tumor or CRC previously treated with no more than 2 prior lines of therapy for advanced disease and progressed or been intolerant to prior standard therapies (Arm C for Part 2 Dose Expansion).
- Measurable disease per RECIST v1.1
- Adequate organ function (bone marrow, liver, kidney, coagulation, endocrine).
- Able to take oral medications.
Exclusion criteria
- Head and neck squamous cell carcinoma.
- Any conditions that may affect the ability to take or absorb study drug.
- Major surgery within 4 weeks prior to receiving study drug(s).
- Patient is unable or unwilling to comply with protocol-required study visits or procedures.
- Other inclusion/exclusion criteria may apply.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 9 centers
- USC Norris Comprehensive Cancer Center — Los Angeles
- Eastern Connecticut Hematology and Oncology Associates — Norwich
- Health Partners Cancer Center at Regions Hospital — Saint Paul
- Tennessee Oncology — Nashville
- MD Anderson Cancer Center — Houston
- MD Anderson Cancer Center — Houston
- NEXT Dallas — Irving
- NEXT Oncology — San Antonio
- … and 1 more center
Identifiers
NCT: NCT07397338 · RMC-APEX-103