AstraZeneca ($AZN) is stepping up its partnership with biotech VentiRx, the Ludwig Cancer Research and the Cancer Research Institute to begin further trials combining its PD-L1 drug with a TLR8 cancer vaccine as the Big Pharma company aims to push on with its cancer immunotherapy.
AstraZeneca's biotech MedImmune, an investor in the Seattle, WA-based VentiRx, will combine its experimental PD-L1 cancer immunotherapy durvalumab in an open-label Phase I/II trial with VentiRx' investigational cancer vax motolimod, added to chemotherapy, in locally advanced or recurrent ovarian cancers that have become resistant to platinum chemotherapy.
The study is being conducted through the CVC Trials Network, which is jointly managed by Ludwig and CRI, in collaboration with MedImmune and VentiRx.
AZ will hope to have better luck in the combo trial after it announced late last year that a study for the drug in lung cancer patients failed to win over the FDA for it to be fast-tracked for approval.
The Anglo-Swedish company projected peak sales of $6.5 billion for durvalumab when it laid out a plan to boost revenue to $45 billion in 2023--but much of this could now rest on the outcome of these types of combo trials.
The researchers expect that motolimod's activation of TLR8 will create conditions within tumors that will enhance the effects of durvalumab. When given with chemotherapy, motolimod could also boost immune responses against cancer cells that are not engaged by durvalumab.
Ovarian cancer has few treatments and suffers from poor diagnosis, although AZ already markets Lynparza, an ADP-ribose polymerase (PARP) inhibitor, that's licensed for ovarian cancer patients who have BRCA gene mutations identified through a genetic test. This combo trial is seeking to expand on this and treat more women who do not have the BRCA gene.
There are currently a number of pharma and biotechs also researching this area, including GamaMabs' immune-activating cancer candidate and Clovis Oncology's ($CLVS) rucaparib.
Durvalumab is being tested in a host of other studies, as a monotherapy or in combination with AZ's investigational cancer drug tremelimumab (which has also had its troubles in recent months) in NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood cancers.
VentiRx' plans for combination studies follow a series of stinging setbacks in the clinic for cancer vaccines, which may be safe but repeatedly proved to be too weak to make a major difference for patients.
Germany's Merck recently dropped its once-ambitious plans for tecemotide (Stimuvax) after reaching the conclusion that its Phase III studies didn't have a shot at success. And GlaxoSmithKline's ($GSK) MAGE A-3 has been a bust in late-stage studies. But VentiRx and others believe that combining vaccines with other agents, including PD-L1 drugs, could offer the best path forward.
PD-1 and PD-L1 cancer immunotherapies are the new hot tickets in oncology, with Merck & Co ($MRK) and BMS ($BMY) gaining first approval for this new class back in 2014, with Roche ($RHHBY) and AstraZeneca now playing catch-up. Roche was in fact last month granted a speedy FDA review for its PD-L1 bladder cancer treatment atezolizumab, while AZ is a little further behind after delays in its programs, and is now likely to be fourth to market in this new class after Roche.
A number of companies are now looking to combine PD-1 and PD-L1 therapies with other cancer agents and just this week, Pfizer ($PFE) announced ne late-stage studies its TKI drug Inlyta with German Merck's anti-PD-L1 drug avelumab for kidney cancer.
- check out the release