Justin Gainor, MD, director, Center for Thoracic Cancers, director of targeted immunotherapy, Massachusetts General Hospital, associate professor of medicine, Harvard Medical School, discusses the potential value of targeting TROP-2 and CEACAM5 in lung cancer.

Over the last decade, the field of lung cancer has been an area of significant progress, according to Gainor. Targeted therapy has expanded rapidly and now there are multiple different oncogenic drivers for which FDA-approved targeted options are available, Gainor says. Additionally, checkpoint inhibitors and cytotoxic chemotherapy are effective for many patients with lung cancer, Gainor adds. 

However, patients who lack an actionable alteration but progress on chemotherapy or immunotherapy are typically treated with single-agent chemotherapy with or without a VEGF inhibitor, Gainor explains. As such, treatment options for this patient population remain an unmet need in lung cancer, Gainor says.

Antibody-drug conjugates (ADCs) could offer a novel approach to treat a significant proportion of patients with lung cancer, who often have upregulation of TROP-2 and CEACAM5, Gainor notes. Moreover, these pathways may offer a vulnerable target in lung cancer that confers sensitivity to ADCs, Gainor concludes.

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Justin Gainor, MD, discusses the potential value of targeting TROP-2 and CEACAM5 in lung cancer.  



Dr. Gainor on the Potential Value of Targeting TROP-2 and CEACAM5 in Lung Cancer 

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, assistant professor of medicine, Harvard Medical School, discusses clinical activity and tolerability of BLU-667 in patients with advanced 

 fusion—positive non–small cell lung cancer (NSCLC).

BLU-667 is a highly potent and selective RET inhibitor targeting oncogenic 

 alterations, including those that confer resistance to multikinase inhibitors. There are no currently FDA-approved RET inhibitors to date. Patients enrolled in the study had 

-altered advanced solid tumors and received 30 mg to 600 mg of oral BLU-667 daily. The first part of the ARROW study determined 400 mg of BLU-667 daily as the recommended dose.

The second part of the ARROW study sought to identify the overall response rate (ORR) and safety of BLU-667. The study enrolled 120 patients, 91 of them having completed prior platinum-based chemotherapy. Of all patients, 84% had received prior therapy; 77% had chemotherapy, 39% had a PD-1/PD-L1 inhibitor, 34% had the combination of chemotherapy and a checkpoint inhibitor, and 18% received a multikinase inhibitor.

Treatment-related toxicity was generally low-grade, with some adverse events including constipation (17%; grade ≥3, 2%), neutropenia (26; grade ≥3, 13%), aminotransferase increase (20%; grade ≥3, 2%), fatigue (13%; grade ≥3, 3%), and hypertension (13%; grade ≥3, 10%).

The preliminary efficacy of BLU-667 was evaluated in 48 patients. Results showed that the ORR was 58% and the disease control rate (DCR) was 96%. Of those 48 patients, 35 received prior platinum-based chemotherapy. In that subgroup, the ORR was 60% and the DCR was 100%.

These data support the expansion of the ARROW trial in treatment-naïve NSCLC patients and continued enrollment of other 

Justin F. Gainor, MD, director of targeted immunotherapy, Massachusetts General Hospital, assistant professor of medicine, Harvard Medical School, discusses clinical activity and tolerability of BLU-667 in patients with advanced RET-fusion+ non-small cell lung cancer (NSCLC).

Justin Gainor, MD

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Dr. Gainor on the Potential Value of Targeting TROP-2 and CEACAM5 in Lung Cancer

Dr. Gainor on Potential With BLU-667 in RET+ NSCLC