Merck Serono has joined the ranks of companies developing anti-PD-L1/PD-1 antibodies, revealing that it has started a phase II trial in an aggressive form of skin cancer.
The mid-stage trial of the company’s candidate – called MSB0010718C – is in patients with metastatic Merkel cell carcinoma (MCC), a cancer which currently has few effective treatment options. The company is planning to enrol approximately 84 patients who have previously received at least one course of chemotherapy.
MCC is a rare and deadly disease which has an approximate mortality rate of 40 per cent with current treatment approaches, primarily chemo- and radiotherapy – and over 80 per cent cases are thought to be caused by viral infection. Its incidence seems to be on the rise around the world.
Merck Serono is also testing the drug in a phase I trial involving a number of other solid tumour types, with a target enrolment of 590 people, in order to identify other potential indications for the drug. It reported data from a study in the first 27 refractory cancer patients at this year’s American Society of Clinical Oncology (ASCO) meeting earlier this year.
Over-expression of PD-L1 has also been seen in melanoma and non-small cell lung, breast, colorectal, prostate, liver, kidney, ovarian, gastro-oesophageal, bladder, and head and neck cancers, as well as glioblastoma multiforme and certain type of haematopoietic malignancies.
MSB0010718C blocks the interaction of PD-L1 with its receptor PD-1 and may have the potential to restore effective anti-tumour immune responses, according to Merck Serono.
The diversity of potential targets for drugs which interact with the PD-L1/PD-1 pathway means that there are plenty of indications to go after and, in selecting MCC, Merck Serono has for now sidestepped the race between Merck & Co’s pembrolizumab and Bristol-Myers Squibb’s (BMS) nivolumab in melanoma and NSCLC.
Roche’s anti-PDL1 drug MPDL-3280A (RG7446) is also being developed in the first instance for NSCLC (phase III) as well as bladder cancer (phase II), while AstraZeneca (AZ) and Novartis are developing earlier-stage candidates across a number of cancer indications. In time there is expected to be a lot of jostling for market share as the cancers most amenable to anti-PD-L1/PD-1 therapy are identified.
In fact, drugs in this category are predicted to become a driver for an explosion in the market for cancer immunotherapies, according to market research firm Decision Resources, which estimates sales will swell from $1.1bn in 2012 to nearly $9bn in 2022 in the US, France, Germany, Italy, Spain, UK and Japan alone.
Away from the PD-L1/PD-1 category however MCC is being targeted by other companies, including GlaxoSmithKline (GSK) which is supporting a phase II trial of its Votrient (pazopanib) in metastatic MCC that is being carried out by Cancer Research UK.
Meanwhile, OncoSec Medical which has an intratumoral immunotherapy for MCC based on interleukin-12 in phase II testing, and Immune Design has started clinical trials of G100, another immunotherapy for the cancer. The latter firm has just announced an initial public offering (IPO) on the Nasdaq.