Syndax Pharma has agreed to test its oral cancer drug entinostat with Merck KGaA and Pfizer’s cancer immunotherapy avelumab in ovarian cancer.
Entinostat is an orally-active drug that is thought to work by inhibiting HDAC and has already attracted the attention of the FDA, getting a breakthrough designation as a treatment for patients with advanced oestrogen receptor-positive breast cancer.
Syndax says that entinostat has a direct effect on cancer cells but also enhances immune system responses, mechanisms that complement the effects of PD-L1 inhibitor avelumab (MSB0010718C) which works by blocking immune-evading processes in tumours.
The drug is in the same class as Novartis’ recently approved panobinostat – used to treat multiple myeloma – and vorinostat from Merck & Co (known as MSD outside the US). It has reached the phase III testing stage in breast cancer, and under the terms of the latest deal Syndax will be responsible for conducting a phase Ib/II clinical trial in ovarian cancer.
Syndax already has agreements in place to test entinostat alongside Merck & Co’s already-marketed PD-1 inhibitor Keytruda (pembrolizumab) in non-small cell lung cancer and melanoma, as well as Roche’s experimental PD-L1 inhibitor atezolizumab in triple-negative breast cancer.
The US company’s chef executive Briggs Morrison – the former AstraZeneca (AZ) R&D head who joined Syndax in last year – said the new deal “reinforces our clinical strategy to explore entinostat for the benefit of patients across a broad range of solid tumour indications”.
The Merck/Pfizer alliance is running a little behind competitors in the PD-1/PD-L1 inhibitor category, which also include Bristol-Myers Squibb with marketed drug Opdivo (nivolumab) and AZ, both in terms of avelumab’s development as a monotherapy and in combination with other drugs.
Recognising that immuno-oncology drugs work best when used in combination, the partners have pledged to increase partnering activities for avelumab.
Avelumab is currently being tested as a therapy for ovarian, gastric, bladder and renal cancers, as well as Merkel cell carcinoma (MCC), for which it has breakthrough status from the FDA.