Eli Lilly and AstraZeneca said today they are expanding a five-month-old immuno-oncology collaboration by exploring across their portfolios the safety and efficacy of additional new combination therapies for patients with solid tumors
The value of the collaboration, other financial terms, and details of the tumors to be studied, were not disclosed.
The companies did say, however, that they will combine AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor durvalumab (MEDI4736) with Lilly molecules designed to target the immune system. These molecules include the TGF-beta kinase inhibitor galunisertib; a CXCR4 peptide antagonist; and an anti-CSF-1R monoclonal antibody—which will also be assessed with AstraZeneca's anti-CTLA-4 monoclonal antibody, tremelimumab.
Lilly will lead the studies, while both companies will contribute unspecified “resources,” the companies said in separate statements.
The expansion builds on a Phase I clinical trial collaboration launched in May, in which the companies agreed to assess MEDI4736 and Cyramza in patients with advanced solid tumors. At the time, the companies said their study had the potential of being expanded.
Developed by AstraZeneca’s global biologics R&D arm MedImmune, durvalumab is a programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitor that is designed to fight cancer by blocking signals from PD-L1 that help tumors avoid detection by the immune system.
Durvalumab was being assessed, alone or with other compounds, in no fewer than 16 clinical studies as of AstraZeneca’s latest pipeline update on June 30—including five Phase III trials. The trials include, among monotherapy indications, third-line non-small cell lung cancer (NSCLC), stage III NSCLC, and second-line squamous cell carcinoma of the head and neck (SCCHN). Durvalumab was also under study in combination with tremelimumab in separate trials for third-line NSCLC and second-line SCCHN (PD-L1 negative).
Galunisertib is in Phase II studies for pancreatic and hepatocellular cancer and glioblastoma. Tremelimumab is in numerous clinical studies, including three Phase III trials—as a monotherapy for mesothelioma; and two combination Phase III trials with durvalimumab: One in third-line NSCLC, the other in 2nd-line SCCHN (PD-L1 negative).
AstraZeneca and Lilly also said they will explore other combinations targeting tumor drivers and resistance mechanisms.
One combination to be studied is Lilly's abemaciclib (CDK4 and 6 small molecule inhibitor) with Faslodex® (fulvestrant) for injection, AstraZeneca's marketed selective estrogen receptor down regulator. Faslodex is indicated for hormone receptor positive metastatic breast cancer in post-menopausal women with disease progression following antiestrogen therapy.
On October 8, Lilly said it received the FDA’s Breakthrough Therapy designation for abemaciclib, which is in two Phase III combination clinical trials: MONARCH 2 to evaluate the combination of abemaciclib and fulvestrant in postmenopausal patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer; and MONARCH 3 to evaluate the combination of abemaciclib and a nonsteroidal aromatase inhibitor in patients with HR+, HER2- locoregionally recurrent or metastatic breast cancer.
Abemaciclib is also under study in the Phase II MONARCH 1 trial as a monotherapy in women with HR+, HER2- metastatic breast cancer.
The companies will also study the combination of AZD9291, AstraZeneca’s investigational third-generation EGFR inhibitor, with both Lilly’s marketed drug Cyramza® (ramucirumab), an anti-VEGFR monoclonal antibody; and Lilly's anti-EGFR monoclonal antibody necitumumab.
As of its June 30 update, AZD9291 was in two Phase III trials as a monotherapy for NSCLC, and two Phase I trials assessing the compound in combinations for NSCLC. Necitumumab is under regulatory review in squamous NSCLC.
In the U.S., Cyramza is approved alone or in combination with paclitaxel for advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Cyramza is also approved in the U.S. in combination with docetaxel for metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy; as well as with Folfiri for metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.