Combining osimertinib and carotuximab for advanced lung cancer treatment

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study investigates the safety and optimal dosing of osimertinib combined with carotuximab in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). It aims to determine the maximum tolerated dose while also evaluating the treatment's effectiveness through various metrics such as objective response rate and progression-free survival. Patients will undergo assessments for dose-limiting toxicities and biomarker evaluations using tumor tissue and circulating tumor DNA.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Stage IV or recurrent/metastatic non-squamous NSCLC that harbors an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q, etc). Local testing for EGFR mutations is acceptable provided it was performed in a CLIA certified lab.
* Part I: Progressive disease on at least one prior EGFR TKI
* Part II, Cohort 1: Progressive disease on osimertinib or other prior EGFR TKIs
* Part II, Cohort 2: Receiving osimertinib as front line treatment for less than 12 weeks. Persistent ctDNA with EGFR mutation between weeks 6-12 from the start of osimertinib treatment.
* Age at least 18
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
* Archival tissue from a biopsy performed after progression of disease on previous EGFR TKI or willing to consent for a fresh tumor biopsy.
* Measurable disease by RECIST 1.1.
* Patients with untreated brain metastases are allowed provided that the patient is clinically asymptomatic and stable.
* Patients must have completed prior chemotherapy ≥ 3 weeks or radiotherapy ≥ 2 weeks prior to receiving study drugs.
* If the subject's most recent line of therapy is treatment with osimertinib, then all adverse events must be resolved to Grade 2 or better
* If the subject's most recent line of therapy is any other treatment than osimertinib, then all Adverse Events must be resolved to grade 1 or better, with the exception of fatigue, alopecia and neuropathy (which must resolve to CTCAE grade 2).
* Adequate organ function
* Women of childbearing potential and men must agree to use adequate contraception while on study.
* Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
* Small cell lung cancer histology.
* Other prior malignancy that might interfere with study endpoints per opinion of the investigator.
* Prior exposure to carotuximab or any CD105 targeted antibody.
* Any major surgical procedure within 2 weeks of starting therapy.
* Patients must not have a history of uncontrolled or poorly-controlled hypertension defined as SBP \> 150 mmHg or DBP \> 90 mmHg within 28 days prior to enrollment.
* Active bleeding or pathologic conditions that carries a high bleeding risk (e.g. gastric ulcers).
* Use of thrombolytics within 10 days prior to the first day of carotuximab.
* Known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies.
* A known diagnosis of Osler-Weber-Rendu syndrome.
* Ascites or pericardial or pleural effusion requiring external drainage procedures.
* New evidence of leptomeningeal disease.
* Acute cardiovascular event within the past 6 months.
* Pregnancy or breastfeeding.

Where it's running

• Cedars-Sinai Cancer at Beverly Hills (THO)
  Beverly Hills, California, United States Recruiting
• Cedars-Sinai Cancer at The Angeles Clinic and Research Institute
  Los Angeles, California, United States Recruiting
• Cedars-Sinai Cancer at SOCC
  Los Angeles, California, United States Recruiting
• Cedars-Sinai Medical Center
  Los Angeles, California, United States Recruiting
• Cedars-Sinai Cancer at Hunt Cancer Center - TMPNCC
  Torrance, California, United States Recruiting

Study contacts

• Principal investigator: Karen Reckamp, MD, MS — Cedars-Sinai Medical Center
• Study coordinator: Clinical Trial Recruitment Navigator
• Email: GroupCancerTrialInformation@cshs.org
• Phone: 310-423-5842

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.