Two immuno-oncology drugs in development at AstraZeneca (AZ) have shown potential as a dual therapy for non-small cell lung cancer, according to a new study.
The phase II trial – reported in Lancet Oncology – found that combining anti-PD-L1 antibody durvalumab with anti-CTLA-4 antibody tremelimumab achieved an overall response rate (ORR) of 23%, significantly higher than has previously been seen with durvalumab alone in this setting.
The trial was small and focused primarily on safety, but the preliminary efficacy signal – albeit in just 26 patients – is encouraging, according to an editorial accompanying the study by Edward Garon of the David Geffen School of Medicine at the University of California, Los Angeles.
Combing two different checkpoint inhibitors in cancer “has a sound scientific basis”, he notes, pointing to clinical experience with the combination of Bristol-Myers Squibb’s PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab) in melanoma.
The trial involved patients with advanced squamous or non-squamous NSCLC, and the combination of durvalumab and tremelimumab showed clinical activity in patients with both PD-L1-positive and PD-L1-negative patients with a “manageable tolerability profile”.
The combination could become a “treatment option for patients with PD-L1 negative tumours whose needs are not addressed by currently available therapies”, according to the authors.
Durvalumab is the flagship drug in AZ’s immuno-oncology programme as it vies to catch up with BMS and Merck & Co, which has already launched PD-1 inhibitor Keytruda (pembrolizumab) onto the market. Opdivo and Keytruda are already approved for NSCLC, while Roche’s atezolizumab candidate is also heading for a marketing application for NSCLC in the coming weeks.
Both durvalumab and tremelimumab have been given fast-track status by the US FDA – in head and neck cancer and mesothelioma respectively. Durvalumab suffered a couple of setbacks towards the end of last year however, which have raised some question marks about its potential.
In December, AZ reported that the single-agent ATLANTIC study of durvalumab in NSCLC was unlikely to be enough to support accelerated approval of the drug, and said it may have to seek approval of the combination of durvalumab and tremelimumab in NSCLC rather than durvalumab alone.
Meanwhile, the company elected to suspend two trials of durvalumab in combination with AZD9291 candidate – an orally-active epidermal growth factor receptor (EGFR) inhibitor – in NSCLC after seeing respiratory complications in some patients.