AstraZeneca to trial a new cancer vaccine with its PD-L1 drug

AstraZeneca ($AZN) will combine its checkpoint inhibitor durvalumab with an experimental cancer vaccine from TapImmune in a midstage trial as it racks up the oncology combo deals with biotechs.

AstraZeneca’s biologics arm MedImmune and the Jacksonville, FL-based biotech will start a Phase II trial of the cancer vaccine TPIV 200--a multi-epitope anti-folate receptor vaccine (FRα)--in combination with AstraZeneca’s PD-L1 drug candidate durvalumab, in patients with platinum-resistant ovarian cancer.

The study will start this quarter and be run at the Memorial Sloan Kettering Cancer Center in New York. The trial will be led by Dr. Jason Konner, a specialist in gynecologic cancers.

This comes just two weeks after the Anglo-Swedish pharma company announced it was teaming up with Seattle, WA-based biotech VentiRx, the Ludwig Cancer Research and the Cancer Research Institute to start early-stage trials combining its PD-L1 drug with the TLR8 cancer vaccine motolimod.

This study too will look at ovarian cancer--specifically, in locally advanced or recurrent ovarian cancers that have become resistant to platinum chemotherapy.

And in February, the pharma giant reported that a combination of durvalumab with the CTLA-4 treatment tremelimumab achieved an objective tumor response rate of 23% for metastatic non-small cell lung cancer patients. Tremelimumab has however fared worse on its own, flunking a mesothelioma trial earlier this year.

Under its new deal with TapImmune, the companies will share clinical costs and comes after TapImmune recently obtained orphan drug designation for TPIV 200 in ovarian cancer from the FDA.

This single arm Phase 2 trial will include 40 women with high-grade ovarian, tubal, or primary peritoneal carcinomas, who have progressed within 6 months of their most recent platinum chemotherapy.

The primary objective of the study is to determine the effectiveness of the combination by measuring ORR and PFS rate at 6 months, with secondary endpoints being safety as well as immune and correlation of FRα-specific immune responses with clinical efficacy. 

"This collaboration is a significant event for TapImmune," said Dr. Glynn Wilson, chairman and CEO of TapImmune.

"We are delighted to bring a leading T-cell vaccine platform into this combination study and to work with AstraZeneca/Medimmune and Sloan Kettering in a patient population that is in dire need of an effective treatment. This study is part of a larger Phase II strategy for TPIV 200 that is designed to greatly increase our understanding of the vaccine while providing clinical evidence of efficacy.

TPIV 200 is a multi-epitope peptide vaccine that targets Folate Receptor Alpha, which is overexpressed in multiple cancers, including over 90% of ovarian cancer cells, according to the biotech.

In Phase I clinical studies conducted at the Mayo Clinic in patients with breast and ovarian cancer, this vaccine was shown to be safe and well tolerated and was able to give cellular immune responses in 20 out of 21 evaluable patients. 

AstraZeneca has not however had the best of luck with its PD-L1 drug, suffering a setback last year late last year after a study in lung cancer patients failed to win over the FDA for it to be fast-tracked for approval.

The Big Pharma 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 will now likely rest on the outcome of these types of combo trials, hence why the company has been ramping up its efforts with biotechs on the drug.

The company was battling to be the third PD1/PD-L1 drugmaker to the market (after Merck ($MRK) and Bristol-Myers Squibb ($BMY)) but looks to have been beaten to the post by Roche’s ($RHHBY) offering atezolizumab, which is set for two FDA approvals this fall.  

This latest combo trial follows recent research suggesting combining checkpoint inhibitors with other oncology meds could increase efficacy in some cancers, with Pfizer ($PFE) recently announcing it would test this theory out by conducting late-stage studies with its TKI drug Inlyta with German Merck's anti-PD-L1 drug avelumab for kidney cancer.

AstraZeneca already markets Lynparza--an ADP-ribose polymerase (PARP) inhibitor--for the disease, with a license for ovarian cancer patients who have BRCA gene mutations identified through a genetic test. It will hope its new drug used in combination will be able to treat more women outside of this mutation.

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