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Genentech Gets FDA Breakthrough Status for NSCLC Therapy; Couples Drug with Roche IHC Test


NEW YORK (GenomeWeb) – The US Food and Drug Administration this week granted breakthrough therapy status to Genentech's anti-PD-L1 cancer immunotherapy MPDL3280A as a treatment for NSCLC patients who have progressed despite treatment with platinum-based chemotherapy and targeted therapy.

In clinical trials for the drug, Genentech is characterizing the PD-L1 expression status of non-small cell lung cancer patients using an immunohistochemistry test developed by parent firm Roche.

"We are committed to personalized healthcare, developing medicines like MPDL3280A with companion tests that may help us identify those who may be appropriate candidates for our medicines," Sandra Horning, Roche’s chief medical officer, said in a statement announcing the second breakthrough therapy designation for the drug.

Last year, the treatment received this designation in the context of bladder cancer. The FDA awards breakthrough status to novel drugs that address unmet medical needs, which places them on an expedited review track.

The agency decided to grant MPDL3280A this designation a second time for NSCLC based on Phase I data presented by Roche two years ago on patients who were heavily pretreated, had advanced disease, and received the anti-PD-L1 agent. In that study, 23 percent of patients responded to MPDL3280A regardless of their PD-L1 status determined by IHC. Among the patients whose tumors the test found to be PD-L1 positive (IHC 2+ or 3+), 46 percent responded, while among those with the highest level of PD-L1 expression (IHC 3+), 83 percent responded.

Most of the adverse events in this early trial were grade 1 or 2. More than 12 percent of patients had grade 3 or 4 toxicities due to MPDL3280A, such as fatigue, shortness of breath, nausea, and vomiting.  

The investigational test being developed by Roche is prospectively determining PD-L1 status for patients enrolled in all studies involving MPDL3280A, according to Roche. The test will gauge PD-L1 expression on tumor cells and on tumor infiltrating immune cells. Although PD-L1 status will be determined in all studies, some trials for MPDL3280A will assess patients' responses to the drug regardless of their PD-L1 expression levels and other trials will enroll only those deemed by testing to be PD-L1 positive.

"Ongoing randomized studies will define what PD-L1 positive means," Holli Dickson, Genentech's senior manager of Genentech's corporate relations told GenomeWeb. In current studies, PD-L1 status is determined on an IHC scoring scale of 0 to 3. A patient is PD-L1 negative if his or her score is 0 or 1, and PD-L1 positive with a score of 2 or 3.

The IHC test will be validated in pivotal studies for MPDL3280A, which are currently ongoing. According to Dickson, Genentech expects to report results from two Phase II trials, called FIR and POPLAR, later this year. The FIR study is a single-arm Phase II trial investigating MPDL3280A in PD-L1 positive patients. POPLAR is a Phase II trial comparing MPDL3280A to docetaxel in NSCLC patients.

There is a third Phase II trial, called BIRCH, which is a single-arm study for MPDL3280A that will enroll PD-L1-positive advanced NSCLC patients. Genentech is also conducting a Phase III trial called OAK in which researchers are comparing the anti-PD-L1 drug against docetaxel in advanced NSCLC patients in the second-line setting.

Dickson noted that MPDL3280A is Genentech's most advanced personalized cancer immunotherapy and is being studied across 19 clinical trials in a variety of cancers, including lung, bladder, skin, breast, kidney cancer and lymphoma. Genentech is planning to launch additional MPDL3280A studies in other tumor types this year. In all these trials, patients' PD-L1 status will be determined by Roche's IHC test. 

"We have discussed our lung and bladder cancer development programs with global health authorities," Dickson said. "But it is too early to speculate on timings for submissions of these indications."