A pair to test against lung cancer

RIDGEFIELD, Conn.—Targeted toward finding a treatment for patients suffering from a specific lung cancer, Boehringer Ingelheim has launched a Phase 2 trial of afatinib (Gilotrif) in combination with pembrolizumab (Keytruda), two drugs aimed at giving patients with locally advanced or metastatic squamous cell carcinoma (SqCC) of the lung a second chance at life. The trial is being conducted in collaboration with a subsidiary of Merck & Co. (known as MSD outside the United States and Canada) and will include approximately 60 patients.

SqCC of the lung is the second-largest subtype of non-small cell lung cancer (NSCLC), representing approximately 20 to 30 percent of NSCLC cases. Patients with advanced SqCC of the lung typically have a poor prognosis, and the median overall survival after diagnosis is around one year.

This Phase 2 trial will evaluate afatinib in combination with PD-1 inhibitor pembrolizumab and assess the efficacy and safety of afatinib plus pembrolizumab in patients with locally advanced or metastatic SqCC of the lung.

Afatinib is already approved in patients with advanced SqCC of the lung whose disease has progressed after treatment with platinum-based chemotherapy, and also in patients with specific types of EGFR mutation-positive NSCLC, as Boehringer Ingelheim continues to explore afatinib beyond the large LUX-Lung program and its current indications.

“Given the complexity of tumors and their ability to evade immune destruction, combination approaches rooted in both clinical and scientific rationale are desperately needed,” states Dr. Benjamin Levy, clinical director of the Sidney Kimmel Cancer Center of Johns Hopkins Medicine in Washington D.C.

“Bringing together two drugs, afatinib and pembrolizumab, which have each demonstrated meaningful activity and survival advantages in advanced-stage squamous cell lung cancer patients, is an attractive strategy that needs to be further investigated as a treatment combination,” Levy states. “The potential synergy in these agents will hopefully advance care and therapeutic options for this group of patients.”

Checkpoint inhibitors, such as pembrolizumab, “interfere with the ability of tumor cells to escape immune surveillance that lead to tumor growth and spread,” Levy tells DDNews. “Afatinib interferes with EGFR signaling, which is active and can contribute to cell growth in many squamous cell cancers.”

Multiple Phase 1/2 trials are currently assessing the combination of a checkpoint inhibitor with an EGFR-TKI in EGFR-mutant NSCLC, including the ongoing Phase 1/1b trial that combines afatinib with pembrolizumab, Levy says.

The Phase 2 trial is being conducted in collaboration with a subsidiary of Merck based on the meaningful activity and survival advantages observed for both agents as monotherapies in second-line treatment of advanced-stage squamous cell lung cancer patients, he says. The trial will include a safety run-in portion to confirm the recommended dose of the combination.

This trial will be conducted in approximately six centers in the United States and in other countries.

“There is no preclinical data for the combination of afatinib with pembrolizumab in SqCC of the lung, but preclinical data suggest that concurrent inhibition of PD-1 and EGFR pathways may represent a rational and promising treatment approach for EGFR-driven tumors,” Levy says.

“Afatinib and pembrolizumab have each demonstrated meaningful activity and survival advantages in advanced-stage squamous cell lung cancer patients, warranting further investigation as a treatment combination in this histological subtype, as well,” he says.

Unfortunately, the use of afatinib and pembrolizumab in combination is not approved as a treatment regimen, Levy adds.

“However, afatinib is approved in the U.S. (Gilotrif), Europe (Giotrif) and other markets in patients with advanced SqCC of the lung whose disease has progressed on or after treatment with platinum-based chemotherapy,” Levy says.

Pembrolizumab is approved in the United States, European Union, Japan and other markets for the treatment of previously untreated patients with metastatic NSCLC whose tumors have high PD-L1 expression with no EGFR or ALK genomic tumor aberrations.

Pembrolizumab is also indicated for the treatment of previously treated patients with metastatic NSCLC whose tumors express PD-L1 as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy.

“This collaboration will provide invaluable information about the use of afatinib and pembrolizumab in combination to treat squamous cell carcinoma of the lung,” states Dr. Martina Flammer, vice president of Clinical Development & Medical Affairs Specialty Care at Boehringer Ingelheim Pharmaceuticals. “Furthermore, the trial underscores our commitment to continually investigate novel approaches for cancer treatment.”