Osimertinib and Carotuximab in Advanced, EGFR-Mutated Non-Small Cell Lung Cancer

What is the Purpose of this Study?

The purpose of this study is to examine the safety and effectiveness of an experimental combination therapy of osimertinib (standard drug) with carotuximab (investigational study drug) in patients who are diagnosed with EGFR-mutated, non-small cell lung cancer. Researchers aim to determine the recommended dose of carotuximab in combination with osimertinib. Carotuximab is a type of antibody, which are normal proteins in the body that help fight infections and possibly cancer. Osimertinib is approved by the U.S. Food and Drug Administration (FDA) to treat patients diagnosed with EGFR-mutated non-small cell lung cancer, but its use in this study is investigational. The study may also use patients’ samples to conduct whole genome sequencing (WGS). WGS is the process of determining the order of DNA building blocks. WGS data may help scientists make new ways to treat, cure or prevent diseases.

Eligibility

* 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.

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.

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Where can I participate?

CS Cancer at Beverly Hills : Garrett Crook
CS Cancer at Cedars-Sinai Medical Center : Garrett Crook
CS Cancer at The Angeles Clinic and Research Institute : Garrett Crook
Hunt Cancer Institute, an Affiliate of Cedars-Sinai Cancer

More about this Clinical Trial

What is the full name of this clinical trial?

IIT2021-12-Reckamp-Osi105: Phase 1 Study of Osimertinib with Carotuximab in Advanced, EGFR-mutated Non-small Cell Lung Cancer

Study Details

Disease Type/Condition

Lung Cancer, Non-small cell

Principal Investigator

Reckamp, Karen

Co-Investigators

Andrew Horodner, Ani Balmanoukian, Cathie T Chung, David Chan, Edwin Posadas, Hugo Hool, Inderjit Mehmi, Iryna Singh, Jeremy Lorber, Justin Moyers, Justin Wayne Tiulim, Kamya Sankar, Kevin Scher, Kristopher Wentzel, Navid Hafez, Omid Hamid, Swati Sikaria, Syed Jilani, Thomas Lowe, Vanessa Dickey, Vi K. Chiu

Age Group

Adult

Phase

IRB Number

STUDY00002130

ClinicalTrials.gov ID

NCT05401110

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Garrett Crook

Garrett.Crook@cshs.org