Boehringer Ingelheim to Evaluate Afatinib in Combination with PD-1 Inhibitor Pembrolizumab in New Tr

Boehringer Ingelheim has announced the initiation of a Phase II trial of afatinib (Gilotrif®) in combination with pembrolizumab (Keytruda®) for patients with locally advanced or metastatic squamous cell carcinoma (SqCC) of the lung.

Benjamin Levy, M.D., Clinical Director, Sidney Kimmel Cancer Center, Johns Hopkins Medicine at Sibley Memorial Hospital Washington DC, said, "Given the complexity of tumors and their ability to evade immune destruction, combination approaches rooted in both clinical and scientific rationale are desperately needed. 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. The potential synergy in these agents will hopefully advance care and therapeutic options for this group of patients."

Afatinib is approved in the U.S. (Gilotrif®), EU (Giotrif®) and other markets in patients with advanced SqCC of the lung whose disease has progressed on or after (EU label) / after (U.S. label) treatment with platinum-based chemotherapy.

Pembrolizumab is approved in the U.S., EU, Japan and other markets for the treatment of previously-untreated patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (tumor proportion score (TPS) >50%) as determined by an FDA-approved test, 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 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy.

The trial is being conducted in collaboration with a subsidiary of Merck (known as MSD outside the United States and Canada) and the combination of afatinib and pembrolizumab studied in this trial is currently not an approved treatment regimen in the studied indication.

"This collaboration will provide invaluable information about the use of afatinib and pembrolizumab in combination to treat squamous cell carcinoma of the lung," said Martina Flammer, M.D., Vice President, Clinical Development & Medical Affairs Specialty Care, Boehringer Ingelheim Pharmaceuticals, Inc. "Furthermore, the trial underscores our commitment to continually investigate novel approaches for cancer treatment."

The Phase II trial will include approximately 60 patients who have progressed or relapsed on or after prior platinum-based chemotherapy, and who have not previously received therapy with an anti-PD-1 therapy or PD-L1/L2 antibody, or other checkpoint inhibitor or anti-EGFR targeted therapy. The trial aims to measure the decrease in tumor size (primary endpoint: objective response rate) and will confirm the dose of afatinib in combination with the standard dose of pembrolizumab, as well as the tolerability of this new regimen. In addition, it will evaluate anti-tumor activity in terms of disease control, duration of response, progression-free survival (PFS), and overall survival (OS).

SqCC of the lung is the second largest sub-type of NSCLC and represents approximately 20-30% 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.