Lung cancer (both small cell and non-small cell) is the second most common cancer diagnosed in both men and women in the United States and the leading cause of cancer death. Researchers at the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) are conducting several clinical trials investigating potential new treatment approaches for patients with non-small cell lung cancer (NSCLC).

NSCLC poses a particular clinical challenge, with 5-year relative survival rates at 65% for early-stage disease, and a dismal 9% for advanced (metastatic) disease (American Cancer Society). Other factors, such as the subtype of NSCLC, gene changes in the cancer cells, age, overall health, and how well the cancer responds to treatment, can also affect a patient’s outlook.

EA5162 – Phase II Study of Osimertinib (AZD9291) in Advanced Non-Small Cell Lung Cancer Patients with Exon 20 Insertion Mutations in EGFR

The study chair for this trial is Zofia Piotrowska, MD, MHS and the study co-chair is Lecia Sequist, MD, MPH (both at Massachusetts General Hospital).

Insertion mutations in EGFR exon 20 are the third most common type of EGFR mutation in NSCLC, comprising 1-10% of all cases, with 4% widely reported. Unfortunately, EGFR exon 20 insertions are insensitive to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs), the usual treatment for most patients with EGFR-mutated NSCLC. This subgroup of patients generally has a median progression-free survival of less than 3 months, and no effective options for targeted therapy for their advanced NSCLC.

Osimertinib (formerly AZD9291) is a third-generation EGFR inhibitor with potent activity against some EGFR mutations—but it has not yet been tested among patients with exon 20 insertions. EA5162 is a phase 2 study testing if osimertinib can effectively inhibit exon 20 insertion mutations and lead to clinical response.

The study aims to enroll 46 patients.

Learn more about the EA5162 trial and view the eligibility criteria.

EA5163/S1709/INSIGNA – A Randomized, Phase III Study of Firstline Immunotherapy alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer with Immunobiomarker SIGNature-driven Analysis

The ECOG-ACRIN study chair for this trial is Hossein Borghaei, DO, MS (Fox Chase Cancer Center) and the SWOG study chair is Anne Chiang, MD, PhD (Yale University/Yale Cancer Center). The ECOG-ACRIN co-chair is Julie Brahmer, MD (Johns Hopkins University/The Sidney Kimmel Comprehensive Cancer Center) and the SWOG co-chair is David Gandara, MD (University of California, Davis/UC Davis Comprehensive Cancer Center).

The standard of care for patients with advanced NSCLC that does not have mutations that can be targeted by TKIs is first-line therapy with a combination of chemotherapy and immunotherapy. However, for patients whose tumors express high amounts of PD-L1, immunotherapy alone may be used. With multiple first-line options available, the EA5163/S1709/INSIGNA trial seeks to discover which of the following treatment approaches is best for patients with PD-L1 high NSCLC: 1) first-line pembrolizumab, then chemotherapy as second-line treatment, 2) first-line pembrolizumab, then chemotherapy and pembrolizumab as second-line treatment, or 3) first-line pembrolizumab and chemotherapy (the current standard of care).

INSIGNA is a collaboration among researchers with ECOG-ACRIN and the SWOG Cancer Research Network.

The study aims to enroll 600 patients.

Learn more about the EA5163/S1709/INSIGNA trial and view the eligibility criteria.

EA5182 – Randomized Phase III Study of Combination Osimertinib (AZD9291) and Bevacizumab versus Osimertinib (AZD9291) Alone as First-Line Treatment for Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer

The study chair for this trial is Helena Yu, MD (Memorial Sloan Kettering Cancer Center) and the study co-chair is Balazs Halmos, MD (Montefiore Einstein Comprehensive Cancer Center).

For patients with metastatic EGFR-mutant lung cancers, the current first-line therapy is an EGFR tyrosine kinase inhibitor (TKI), most often osimertinib. However, single-agent osimertinib is only effective for a limited period, and few choices exist upon progression outside of chemotherapy-based approaches. Combination approaches to first-line treatment are needed to improve upon the current standard of care.

EA5182 is an important phase 3 study to assess whether adding the VEGF inhibitor bevacizumab to osimertinib as first-line treatment improves outcomes for this patient population. The combination of these drugs could prolong progression-free survival and delay the need for systemic chemotherapy, improving patient quality of life, delaying central nervous system progression, and possibly culminating in an overall survival benefit.

The study aims to enroll 300 patients.

Learn more about the EA5182 trial and view the eligibility criteria.

E4512, an ALCHEMIST Trial – A Randomized Phase III Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Observation for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

The study chair for this trial is David Gerber, MD (UT Southwestern/Simmons Cancer Center-Dallas) and the study co-chairs are Corey Langer, MD (University of Pennsylvania/Abramson Cancer Center) and Onkar Khullar, MD (Emory University/Winship Cancer Institute).

Surgical resection leads to cure rates of approximately 25-70% for patients with early-stage NSCLC. For those whose cancer returns, most recurrences appear at distant sites, suggesting that micrometastasis is an early event. Additionally, pilot studies have documented the presence of micrometastatic cells in the bone marrow of patients with early-stage disease. Thus, eradication of micrometastatic disease is an important objective following surgery. The current standard of care is adjuvant chemotherapy—but survival rates continue to be less than 50% at 5 years for stage 2 and 3 disease.

E4512, an ALCHEMIST Trial, is testing the use of adjuvant crizotinib in patients with early-stage NSCLC whose tumors harbor the anaplastic lymphoma kinase (ALK) fusion protein. Crizotinib is an inhibitor of the MET, ALK, ROS1, and RON tyrosine kinases, and is approved by the U.S. Food and Drug Administration to treat ALK-positive patients with advanced NSCLC. Researchers will evaluate if adjuvant therapy with crizotinib results in improved disease-free survival compared to observation.

The study aims to enroll 168 patients.

Learn more about the EA5182 trial and view the eligibility criteria.