Combining osimertinib and carotuximab for advanced lung cancer treatment

IIT2021-12-Reckamp-Osi105: Phase I Study of Osimertinib With Carotuximab in Advanced, EGFR-mutated Non-Small Cell Lung Cancer

This study is testing a new combination of two drugs, osimertinib and carotuximab, to see if it can safely help people with advanced lung cancer caused by specific genetic changes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cedars-Sinai Medical Center (Academic / other)
• Drugs / interventions: carotuximab, osimertinib, chemotherapy, radiation
• Locations: 5 sites (Beverly Hills, California and 4 other locations)
• Trial ID: NCT05401110 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates include adults with stage IV or recurrent/metastatic non-squamous NSCLC harboring specific EGFR mutations who have experienced disease progression on prior treatments.

Not a fit: Patients with early-stage lung cancer or those without EGFR mutations are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced EGFR-mutated NSCLC.

How similar studies have performed: While the combination of osimertinib and carotuximab is a novel approach, previous studies have shown promise in targeting EGFR mutations in lung cancer.

Eligibility criteria

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 this trial is running

Beverly Hills, California and 4 other locations

• 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

Conditions Non Small Cell Lung Cancer; Lung Cancer; EGFR; Osimertinib; Carotuximab