Kairos Pharma reports interim Phase 1 data showing no Grade 3 or higher ENV-105-related toxicities in 13 patients receiving carotuximab with osimertinib for EGFR-mutated NSCLC.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Kairos Pharma has reported encouraging interim safety findings from its ongoing Phase 1 study (NCT05401110) evaluating ENV-105 (carotuximab) in combination with osimertinib (Tagrisso®) for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) who have developed resistance to osimertinib. Across the first 13 treated patients, no Grade 3 or higher toxicities related to ENV-105 were observed, supporting continued clinical development of the combination and progression toward an early efficacy assessment.
The study addresses a major therapeutic challenge in EGFR-mutated NSCLC, where most patients eventually develop resistance to osimertinib despite initial clinical benefit. Once resistance emerges, treatment options remain limited, highlighting the need for therapies that can restore sensitivity to EGFR-targeted treatment rather than replace it.
Scientific Rationale for Targeting CD105
ENV-105 is a first-in-class monoclonal antibody targeting CD105 (endoglin), a protein implicated in tumor progression and therapeutic resistance. Preclinical research suggests CD105 expression increases as tumors acquire resistance to osimertinib, activating signaling pathways that promote continued cancer growth despite EGFR inhibition.
By blocking CD105, ENV-105 is intended to disrupt these resistance mechanisms and potentially restore tumor responsiveness to osimertinib. If validated in clinical studies, this strategy could prolong the effectiveness of first-line EGFR-targeted therapy and delay disease progression in patients with resistant disease.
Non-small cell lung cancer accounts for approximately 85% of all lung cancer diagnoses worldwide, with EGFR-mutated tumors representing a clinically important subgroup that routinely receives osimertinib as first-line therapy.
Interim Phase 1 Safety Findings
The ongoing Phase 1 trial is evaluating the safety, tolerability, dose-limiting toxicities, and recommended Phase 2 dose of ENV-105 in combination with osimertinib in patients with advanced EGFR-mutated NSCLC.
According to the interim analysis
- Thirteen patients have received combination therapy.
- No Grade 3 or higher toxicities associated with ENV-105 have been reported.
- No serious safety signals have emerged during treatment.
- Reported adverse events have been manageable with standard supportive care.
- Safety assessments are being conducted using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Although efficacy data have not yet been reported, the favorable safety profile supports continued dose escalation and future evaluation of the combination’s ability to overcome acquired resistance to osimertinib.
Clinical Perspective from Company Leadership
John Yu, MD, Chief Executive Officer of Kairos Pharma, said the interim findings strengthen confidence in the company’s strategy of restoring sensitivity to existing targeted therapies rather than developing competing treatments. He noted that confirming a favorable safety profile represents an important milestone as the program advances toward evaluating clinical benefit in patients who have progressed on osimertinib.
Neil Bhowmick, PhD, Chief Science Officer, added that ENV-105 has now demonstrated favorable tolerability across multiple oncology programs, reinforcing the potential of CD105 inhibition as a therapeutic approach for overcoming treatment resistance.
Clinical Path
Kairos will continue enrolling patients in the Phase 1 trial to establish the recommended Phase 2 dose and generate preliminary efficacy data. The program represents the company’s lead effort to validate CD105 inhibition as a strategy for reversing acquired resistance to EGFR-targeted therapy in advanced NSCLC.
Beyond lung cancer, ENV-105 is also under clinical evaluation in metastatic castration-resistant prostate cancer, reflecting broader interest in targeting CD105-mediated resistance pathways across multiple solid tumors. Early efficacy findings from the ongoing NSCLC study will be closely watched to determine whether the promising safety profile translates into meaningful clinical benefit for patients with limited treatment options.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.