Eli Lilly and Company announced additional results from its global, randomized, double-blind, placebo-controlled phase 3 RANGE trial evaluating Cyramza (ramucirumab) in combination with docetaxel in patients with locally advanced or unresectable or metastatic urothelial carcinoma whose disease progressed on or after platinum-based chemotherapy. A positive trend was seen in the secondary endpoint of overall survival (OS) which did not reach statistical significance. An improvement in objective response rate (ORR) was observed.
 
Lilly previously announced that the trial met its primary endpoint of investigator-assessed progression-free survival (PFS); those results were presented at the European Society for Medical Oncology (ESMO) 2017 Congress and simultaneously published in The Lancet. RANGE is the only phase 3 study to demonstrate superior PFS compared to chemotherapy in a post-platinum setting in advanced urothelial carcinoma. Additionally, RANGE is the first Phase 3 trial to show the benefit of targeting angiogenesis in urothelial carcinoma.

No new safety signals were observed. The safety profile observed in the RANGE study was consistent with what was seen previously in this trial and what has been previously observed for Cyramza. The efficacy and safety results will be submitted for presentation at a future medical meeting.

"People with advanced urothelial carcinoma who experience disease progression urgently need treatment options that can control the disease – to help stop or slow the cancer from growing and spreading," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "Although this study didn't reach statistical significance for overall survival, we are encouraged by the totality of the RANGE results and look forward to reviewing the data with internal and external experts to determine next steps."

Lilly sincerely appreciates and thanks the patients, investigators and clinical trial sites for their participation in and support of this study.

Lilly remains committed to the investigation and use of Cyramza in other tumor types, including those in which it has already demonstrated a phase 3 overall survival benefit – stomach, non-small cell lung, colorectal and liver cancer.

The RANGE trial, which enrolled 530 patients globally, is a randomized, double-blind study designed to evaluate the safety and efficacy of Cyramza and docetaxel versus placebo and docetaxel in patients with locally advanced or unresectable or metastatic urothelial carcinoma whose disease progressed on or after platinum-based chemotherapy. The trial includes: 1) patients whose disease progressed following adjuvant and/or neoadjuvant therapy; 2) patients whose disease progressed following first-line therapy for metastatic disease; and 3) patients who had received prior platinum-based and immune checkpoint inhibitor regimens. The trial's primary endpoint is investigator-assessed progression-free survival, and other secondary endpoints include overall survival, objective response rate, disease control rate and patient-reported outcomes.

Urothelial cancer includes carcinomas that arise in the urothelial or transitional cells that line the urinary collecting system, including the bladder, which is the most common site for this type of tumor. Other potential primary sites of this cancer include the renal pelvis, ureter and urethra. Bladder cancer accounts for the majority of all urothelial carcinoma.

Worldwide, bladder cancer ranks ninth in the topmost common cancers overall, and the ninth leading cause of cancer-related deaths, afflicting approximately 430,000 people per year and resulting in more than 165,000 deaths. The global incidence of bladder cancer increased 11 per cent from 2008 to 2012.  In the US, bladder cancer is the sixth most common and deadly cancer, with an estimated 81,190 new cases and 17,240 deaths expected in 2018.

Generally, this is an aggressive disease and, unfortunately, despite recently approved therapies, the majority of patients who have disease progression will eventually succumb to their cancer.

Angiogenesis is the process of making new blood vessels. In a person with cancer, angiogenesis creates new blood vessels that give a tumor its own blood supply, allowing it to grow and spread.

Some tumors create proteins called VEGF. These proteins attach to the VEGF receptors of blood vessel cells causing new blood vessels to form around the tumors, enabling growth. Blocking the VEGF protein from linking to the blood vessels helps to inhibit tumor growth by slowing angiogenesis and the blood supply that feeds tumors. Of the three known VEGF receptors, VEGF Receptor 2 is linked most closely to VEGF-induced tumor angiogenesis.

In the US, Cyramza (ramucirumab) is approved for use as a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy. It is also approved in combination with docetaxel as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy. Additionally, it is approved with FOLFIRI as a treatment for people with metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Cyramza is being investigated in a broad global development program that has enrolled more than 12,000 patients across more than 70 trials worldwide. These include several studies investigating Cyramza in combination with other anti-cancer therapies for the treatment of multiple tumor types.

Cyramza is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. Cyramza inhibited angiogenesis in an in vivo animal model.

Cyramza, as a single agent or in combination with paclitaxel, is indicated for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

Cyramza, in combination with docetaxel, is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Cyramza.

Cyramza, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.