Roche’s Tecentriq Glows In Pivotal Trial For Early Lung Cancer
Immunotherapy Improves DFS In Early NSCLC
Executive Summary
Positive pivotal results with Tecentriq in early post-surgery lung cancer should give Roche’s PD-L1 inhibitor pole position within its class for the blockbuster indication. But rivals are hot on its tail.
Roche Holding AG’s Tecentriq (atezolizumab) looks likely to become the first programmed cell death protein-based therapy to be approved in early lung cancer after pivotal IMPower010 study showed that the PD-L1 inhibitor helped people with the condition live longer without their disease returning.
But strong competitors are advancing quickly in the setting – with results of Merck & Co., Inc.'s Phase III adjuvant Keytruda study (KEYNOTE-091) also keenly awaited later this year – meaning Roche may only have a few months to capitalise on any first-mover advantage it may obtain with the data.
IMPower 010 is the first Phase III study to show that a cancer immunotherapy can improve disease-free survival (DFS) in people with resectable early-stage non-small cell lung cancer compared with best supportive care, the Swiss pharma said when announcing the topline results on 22 March.
The data support the assumption that treating lung cancer early, before it has spread, with a checkpoint inhibitor may help prevent the disease from returning and therefore provide the best opportunity for a cure.
The pivotal trial included patients with completely resected Stage Ib-IIIa NSCLC and is looking at DFS in the PD-L1 subpopulation within the Stage II-IIIa population, in all randomized patients with Stage II-IIIa NSCLC, and in the intent-to-treat (ITT) population as its primary endpoint.
At the interim analysis, “Tecentriq showed a statistically significant improvement in DFS as adjuvant therapy following surgery and chemotherapy in all randomised Stage II-IIIa populations with NSCLC. The magnitude of DFS benefit was particularly pronounced in the PD-L1-positive population,” Roche said. Safety was consistent with Tecentriq’s known safety profile and no new safety signals were identified.
A bigger picture will need to wait, however. Follow-up reports will continue with the planned analyses of DFS in the overall ITT population, which at the time of this interim analysis did not cross the threshold, and overall survival (OS) data (a secondary endpoint), which were immature at the time of interim analysis, the company said. Once compiled, overall data from the IMpower010 study will be presented at an unidentified medical meeting later this year and submitted to health authorities globally, including the US Food and Drug Administration and the European Medicines Agency, Roche said.
Analysts were impressed by the topline IMPower010 results, saying the data should boost Tecentriq’s competitive chances as a treatment for NSCLC. It was the third PD-1/PD-L1 inhibitor approved in that indication and has struggled to overcome the sizable competition posed by Merck’s Keytruda and Bristol Myers Squibb Company's Opdivo (nivolumab).
“This update is certainly a strong positive update for Roche in NSCLC,” said Zachary McLellan, therapeutic area director for oncology and respiratory at Datamonitor Healthcare. “Still, without specific results it’s difficult to determine Tecentriq’s outlook in this segment, but a potential first-to-market advantage would certainly bolster potential uptake. Strong improvements in the ITT population, as well as an OS improvement would further improve Tecentriq’s use case,” McLellan added.
Tecentriq is already approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of NSCLC, SCLC, certain types of metastatic urothelial cancer, in PD-L1-positive metastatic triple-negative breast cancer and for hepatocellular carcinoma. In the US, Tecentriq is also approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma.
“We are seeing a shift towards treating cancer earlier; as large populations that are predominantly untapped for the Programmed Death therapies and for those cancers that can be detected early, the pre-surgery and post-surgery populations are a significant opportunity. However, to date the data in early cancer has been mixed,” analysts at Bernstein said in a same-day reaction note.
Roche has several Phase III early cancer trials evaluating Tecentriq. In addition to the post-surgery IMpower010 and pre-surgery IMpower030 trials in NSCLC, it has studies in head and neck cancer, HER-2 positive breast cancer and renal cell carcinoma.
Competition
Merck’s Keytruda is not far behind in the adjuvant NSCLC setting with topline results from the Phase III KEYNOTE-091 trial expected later this year.
“We also expect Opdivo to be approved and see use in the peri-adjuvant setting for early-stage NSCLC based on the Phase III CheckMate-77T trial,” McLellan told Scrip.
Results from that study are not expected until 2022 at the earliest. As such, Tecentriq would quickly face strong competition from the more established PD-1 inhibitors. “And unless Tecentriq’s data are significantly superior, we forecast Opdivo to compete well with Tecentriq, and Keytruda to become the early-stage class leader,” McLellan said.
Analysts at Jefferies agreed, adding in a reaction note that “we already assume that Keytruda will be a preferred option and think Tecentriq could achieve around 25% market share for adjuvant NSCLC.”