July 13, 2015
By Mark Terry, BioSpace.com Breaking News Staff
South San Francisco, Calif.-based Genentech announced positive results today for its urothelial bladder cancer (UBC) drug atezolizumab, or MPDL3280A. On Feb. 2, 2015, the U.S. Food and Drug Administration (FDA) granted the drug a second Breakthrough Designation.
The drug, a monoclonal antibody that interferes with a protein called PD-L1, was part of the IMvigor 210 Phase II clinical trial. The study has two cohorts. One is made up of patients who had no prior therapy for advanced or metastatic UBC, but were not eligible for first-line cisplatin therapy. Findings have not yet been released on this cohort. The second cohort, which are the results announced today, involved patients whose diseases had progressed during or after previous treatment with platinum-based therapy.
Of Cohort 2, patients receiving the drug met the primary endpoint, which was the tumors shrinking with an objective response rate (ORR).
“We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study because minimal progress has been made in advanced bladder cancer for nearly 30 years,” said Sandra Horning, Genentech’s chief medical officer and head of global product development in a statement. “We plan to present results at an upcoming medical meeting, and will discuss next steps with health authorities to bring a new treatment option to patients as soon as possible.”
Anti-PD-L1 is the hot new area in cancer drug research. On June 2, 2015, Amgen announced a collaboration with Roche on a Phase Ib clinical trial to evaluate talimogene laherparepvec combined with atezolizumab (MPDL3280AA) for the treatment of triple-negative breast cancer and colorectal cancer with liver metastases.
“Atezolizumab is our most advanced cancer immunotherapy with 10 ongoing Phase III pivotal trials across lung, bladder, breast and kidney cancers,” said Horning at the time in a statement.
On May 29, 2015, Amgen announced a deal with Merck & Co. to expand their collaboration on talimogene with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, in a Phase I, open-label trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).
On Nov. 17, 2014, Pfizer Inc. (PFE) and Merck KgaA , headquartered in Darmstadt, Germany, announced that the two companies were working on an anti-PD-L1 antibody. In that deal, Pfizer Inc. paid Merck an upfront fee of $850 million, as well as up to $2 billion in regulatory and commercial milestone payments. The drugs are being studied on non-small cell lung cancer, ovarian cancer and Merkel cell carcinoma, a rare type of skin cancer.
“Immuno-oncology is a top priority for Pfizer,” said Albert Bouria at the time in a statement. Bouria is group president Vaccines, Oncology and Consumer Healthcare Businesses for Pfizer. “Combining this promising anti-PD-L1 antibody with Pfizer’s extensive portfolio of small molecules and antibodies, provides an opportunity to potentially broaden the use of immunotherapy for patients with cancer and rapidly expand our oncology business.”
Merck’s Keytruda had such positive Phase III trials that on Mar. 24, 2015 the company ended its KEYNOTE-006 clinical trial early after it met its two primary endpoints. That trial was in patients with advanced melanoma.
Bristol-Myers Squibb Company announced on Mar. 4, 2014 that it was developing and marketing Prostvac, Bavarian Nordic A/S ’s investigational Phase III prostate-specific antigen (PSA)-targeting cancer immunotherapy for prostate cancer. Bristol-Myers is planning a Phase II study that investigates a combination of Prostvac with Yervoy, which is a PD-1 inhibitor.
The FDA approved Bristol-Myers Squibb’s Opdivo (nivolumab), a PD-1 pathway inhibitor, for the treatment of metastatic melanoma in 2014. It also granted the drug breakthrough designation, priority review and orphan product designation.
The PD-1/PD-L1 pathway has been identified in cancer as significant in helping tumors avoid being destroyed by the body’s immune reaction. Compounds that disrupt this pathway show prime for a number of different cancer therapies.
