Afatinib to be evaluated in combination with PD-1 inhibitor pembrolizumab in new trial for patients with squamous cell carcinoma of the lung
Efficacy and safety of afatinib plus pembrolizumab to be assessed in Phase II trial in patients with locally advanced or metastatic squamous cell carcinoma (SqCC) of the lung
Afatinib is approved in patients with advanced SqCC of the lung whose disease has progressed after treatment with platinum-based chemotherapy and in patients with specific types of EGFR mutation-positive non-small cell lung cancer (NSCLC)
Boehringer Ingelheim continues to explore afatinib beyond the large LUX-Lung programme and its current indications
Ingelheim, Germany, 09 February 2017 – Boehringer Ingelheim today announced the initiation of a Phase II trial of afatinib* (Giotrif®) in combination with pembrolizumab (Keytruda®) for patients with locally advanced or metastatic squamous cell carcinoma (SqCC) of the lung.
Benjamin Levy, MD, Clinical Director, Sidney Kimmel Cancer Center, Johns Hopkins Medicine at Sibley Memorial Hospital Washington DC, USA said, “Given the complexity of tumours 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 EU (Giotrif®), US (Gilotrif®) and other markets in patients with advanced SqCC of the lung whose disease has progressed on or after (EU label) / after (US label) treatment with platinum-based chemotherapy.
Pembrolizumab is approved in the US, EU, Japan and other markets for the treatment of previously-untreated patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have high PD-L1 expression (tumour proportion score (TPS) >50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumour aberrations. Pembrolizumab is also indicated for the treatment of previously-treated patients with metastatic NSCLC whose tumours 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 & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the US and Canada) and the combination of afatinib and pembrolizumab studied in this trial is currently not an approved treatment regimen in the studied indication.
Dr Victoria Zazulina, Medical Head, Solid Tumour Oncology, Boehringer Ingelheim said, “We are excited to collaborate with MSD and launch this trial, allowing us to gain further insights into the opportunities around treatment of squamous cell carcinoma of the lung. Around the world, patients with this type of cancer are already benefitting from anti-PD-1 therapies and afatinib, the only oral tyrosine kinase inhibitor (TKI) used in this indication. It is intriguing to combine both approaches in an attempt to improve the outcomes for patients with squamous lung cancer and equip physicians with new options.”
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, a PD-L1/L2 antibody, or other checkpoint inhibitor or anti-EGFR targeted therapy. The trial aims to measure the decrease in tumour 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-tumour 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.1,2 Patients with advanced SqCC of the lung typically have a poor prognosis and the median overall survival after diagnosis is around one year.3,4
Afatinib is also approved in over 70 countries for the first-line treatment of EGFR mutation-positive NSCLC and continues to be more broadly studied beyond the approved indications.
Notes to editors
Intended audiences This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.
Afatinib* is approved in the EU (Giotrif®), US (Gilotrif®) and other markets in patients with advanced SqCC of the lung whose disease has progressed on or after (EU-label) / after (US label) treatment with platinum-based chemotherapy.
Approval of afatinib in this indication is based on results of the LUX-Lung 8 study, which showed a significantly improved OS and PFS compared to Tarceva® (erlotinib) in patients with SqCC of the lung.5
LUX-Lung 8 is part of the LUX-Lung programme – the largest collection of clinical trials of any EGFR TKI, with over 3,760 patients across eight studies conducted across the world.
Afatinib is also approved in over 70 countries for the first-line treatment of EGFR mutation-positive NSCLC.
Approval of afatinib in this indication was based on the primary endpoint of PFS from the LUX-Lung 3 clinical trialwhere afatinib significantly delayed tumour growth when compared to standard chemotherapy. 6
In addition, afatinib is the first treatment to have shown an OS benefit for patients with specific types of EGFR mutation-positive NSCLC compared to chemotherapy.7 A significant OS benefit was demonstrated independently in the LUX-Lung 3 and 6 trials for patients with the most common EGFR mutation (del19) compared to chemotherapy.7
Most recently in the LUX-Lung 7 trial, a reduction in the risk of death was observed for patients treated with afatinib versus Iressa® (gefitinib), in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC, without reaching significance.8
About Boehringer Ingelheim
Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally through 145 affiliates and a total of some 50,000 employees. The focus of the family-owned company, founded in 1885, is on researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.
Social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects through, for example, the initiative “Making More Health” while also caring for employees. Respect, equal opportunity and reconciling career and family form the foundation of mutual cooperation. The company also focuses on environmental protection and sustainability in everything it does.
In 2015, Boehringer Ingelheim achieved net sales of about 14.8 billion euros. R&D expenditure corresponds to 20.3 per cent of net sales.
Pembrolizumab is marketed by Merck & Co under the brand name Keytruda®.
*Afatinib is approved in more than 70 countries, including the EU, Japan, Taiwan and Canada under the brand name Giotrif®, in the US under the brand name Gilotrif® and in India under the brand name Xovoltib® for use in patients with distinct types of EGFR mutation-positive NSCLC. Afatinib is also approved in the EU, US and other markets for the treatment of patients with advanced SqCC of the lung whose disease has progressed (on or) after treatment with platinum-based chemotherapy. Afatinib is under regulatory review by health authorities in other countries worldwide. Registration conditions differ internationally, please refer to locally approved prescribing information.
1 Travis WD. Pathology of Lung Cancer. Clin. Chest Med. 2011;32(4):669–692.
2 Hall PE, et al. Rationale for targeting the ErbB family of receptors in patients with advanced squamous cell carcinoma of the lung. Future Oncol. 2015;11(15):2175-91.
3 Cancer Monthly. Lung Cancer (NSCLC). Available at: http://www.cancermonthly.com/cancer_basics/lung.asp. Accessed December 2016.
4 Cetin K, et al. Survival by histologic subtype in stage IV non-small cell lung cancer based on data from the Surveillance, Epidemiology and End Results Program. Clin Epidemiol. 2011;3:139–148.
5 Soria JC, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol 2015;DOI:10.1016/S1470-2045(15)00006-6.
6 Sequist L, et al. Phase III Study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with epidermal growth factor receptor mutations. J Clin Oncol 2013;DOI:10.1200/JCO.2012.44.2806.
7 Yang J, et al. Afatinib versus cisplatin chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015; http://www.thelancet.com/journals/lancet/article/PIIS1470-2045(14)71173-8/abstract.
8 Paz-Ares L, et al. Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC): overall survival (OS) data from the phase IIb trial LUX-Lung 7 (LL7). Abstract # LBA43 presented at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen, Denmark, 7 – 11 October.