Roche's IMpower130 Met Co-Primary Endpoints, Lifting ASCO Suspense
Executive Summary
Roche said its Phase III IMpower130 study met its co-primary endpoints of overall survival and progression-free survival in the advanced first-line setting for non-squamous lung cancer.
Hoping to further support Tecentriq (atezolizumab) in lung cancer, Roche said its Phase III IMpower130 combo study met its co-primary endpoints of overall survival and progression-free survival, and that the anti-PD-L1 MAb plus chemotherapy helped people with metastatic non-squamous non-small cell lung cancer (NSCLC) live "significantly longer" compared to chemotherapy alone.
The top-line data, announced May 29, builds on positive results of the IMpower 150 and IMpower131 trials using Tecentriq, and will heighten suspense ahead of the coming American Society of Clinical Oncology (ASCO) annual meeting, to be held June 1-4 in Chicago, which observers expect to offer an exciting showdown in treatment options for both squamous NSCLC and the first-line setting in non-squamous NSCLC.
IMpower130 #3 Of 8 Pivotal Tecentriq Trials
IMpower130 is Roche’s third pivotal trial success in evaluating Tecentriq alone or in combination to demonstrate an overall survival benefit for people with NSCLC.
Roche has eight Phase III lung cancer studies underway testing the anti-PD-L1 by itself or with other therapies. The compound is a monoclonal antibody designed to bind with the PD-L1 protein.
Still, analysts say Merck & Co. Inc.'s PD-1 inhibitor Keytruda (pembrolizumab) is leading the race within its class for lung cancer.
The non-squamous NSCLC market represents some 70% of diagnosed first-line lung cancer patients, and is being investigated by current I-O trials such as Keynote 189, Checkmate 227, MYSTIC and the Roche IMpower130/132 studies.
The combination of Keytruda with Eli Lilly & Co.'s Alimta (pemetrexed) and paclitaxel or carboplatin received accelerated approval last year for first-line non-squamous NSCLC, based on Phase II cohort data from the KEYNOTE-021G study, and is positioned to get full approval in this indication based on the Phase III KEYNOTE-189 study. (Also see "Merck's Keytruda Enjoys Clean Sweep In Lung Cancer, At Bristol's Expense" - Scrip, 17 Apr, 2018.)
"With Keynote-189 now setting the efficacy bar, the market will need to see how these [IMpower130] results and those from IMpower132, which utilizes the comparable chemo regime, compare," analysts at Jefferies said in a note dated May 29.
Keytruda is already approved as a monotherapy for first-line PD-L1+ squamous patients, a group representing around 30% of diagnosed first-line lung cancer patients.
Datamonitor Healthcare analyst Michael Ramirez noted that only Keytruda and Tecentriq have reported OS benefit in this setting, "with Tecentriq now showing benefit when combined with Avastin and chemotherapy in non-squamous NSCLC in IMpower150 as well as when combined with carboplatin and nab-paclitaxel in non-squamous NSCLC in IMpower130."
The IMpower130 trial examined the efficacy and safety of Tecentriq combined with carboplatin and Celgene Corp.'s Abraxane (nab-paclitaxel) chemotherapy regime, versus chemotherapy comprising carboplatin and Abraxane alone in the first-line treatment of advanced non-squamous NSCLC. Roche said it showed the Tecentriq based regimen helped people live significantly longer compared to chemotherapy alone in this first-line setting and also reduced the risk of disease worsening or death. No new safety signals were identified with the combination, it added.
A picture of the absolute magnitude of the benefit seen in the IMpower130 study will first come later this year, however. Detailed data from the randomized study in 724 patients would be presented at "an upcoming oncology congress", Roche said without elaborating.
Tecentriq is already approved in the EU, US and more than 70 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.
ASCO To Hear IMpower150 Details
In April, Roche said its IMpower150 trial showed Tecentriq plus Avastin (bevacizumab) plus paclitaxel and carboplatin significantly improved progression free survival compared to Avastin and chemo alone making the drug a first-line lung cancer contender.
The IMpower150 trial – details of which will be presented at ASCO June 4 - showed OS advantage in all prespecified exploratory biomarker-selected subgroups analysed, which included people with EGFR- and ALK-positive mutations who had received an appropriate targeted therapy, and those with varying levels of PD-L1 expression or with negative PD-L1 expression. People with liver metastases treated with the Tecentriq combination also had a survival advantage, Roche said.
The analysts at Jefferies summarized the IMPower130 announcement by saying it "builds on the success of IMpower150, which utilised Tecentriq and Avastin on top of chemo, and the IMpower131 trial that also used an Abraxane-based chemo regimen, but in the first-line squamous NSCLC setting."
"We currently model around $4.4bn of peak sales for Tecentriq in the first-line NSCLC setting across both the squamous and non-squamous settings, which also reflects Keytruda’s likely lead with the Alimta combination following the results of the KEYNOTE-189 study."
Datamonitor Healthcare's Ramirez believes that if the three trials - IMpower150, IMpower130 and IMpower131 - result in regulatory approvals, then "Tecentriq stands to capture the entire first-line setting, including both squamous and non-squamous histologies regardless of PD-L1 expression, with the added option of an Avastin-containing regimen in non-squamous NSCLC."
Despite Tecentriq’s potential approvals, however, Ramirez says Merck's Keytruda "is likely to remain the preferred PD-1/PD-L1 inhibitor in the first-line non-squamous NSCLC population, as it is approved in combination with Alimta and carboplatin, based on KEYNOTE-21G and KEYNOTE-189, the standard-of-care chemotherapy backbone for this setting."
"So while Tecentriq will still experience significant uptake upon approval, it is unlikely to gain more market share than Keytruda in this setting," he concluded.