Roche’s oncology department, especially the solid tumor franchise, has suffered a series of losses just as it tries to combat biosimilar competition to its old cancer troika.
The latest setback? Tecentriq has failed a phase 3 test in postsurgery kidney cancer, Roche said in an investor presentation Thursday.
The IMmotion010 trial tested Tecentriq as an adjuvant therapy in patients with renal cell carcinoma at high risk of developing metastasis after surgical removal of kidney tissue. Investigators wanted to see if the drug can prevent disease recurrence or death.
The flop pushes the Roche PD-L1 inhibitor further away from Merck & Co.’s leading PD-1 inhibitor Keytruda, which got immunotherapy’s first FDA go-ahead in adjuvant kidney cancer in November. SVB Securities analyst Daina Graybosch, Ph.D., has put the adjuvant kidney cancer market opportunity at $3.4 billion for PD-1/L1 inhibitors.
In addition to the failure, Roche also pushed back a potential Tecentriq readout in head and neck cancer from 2022 to 2023. An independent drug review committee has evaluated the data at an interim analysis and suggested that the trial continue, Roche pharma chief Bill Anderson said on a call Thursday.
Kidney cancer is somewhat of a wild card for Tecentriq; the drug currently doesn’t have an indication in metastatic kidney cancer. But Tecentriq has two other key trials in early-stage liver cancer and non-small cell lung cancer that could read out this year, and both are in relatively familiar territory for the treatment.
Tecentriq, used alongside Avastin, is currently the only PD-1/L1 inhibitor allowed in previously untreated liver cancer thanks to a 2020 approval, whereas both Keytruda and Bristol Myers Squibb’s Opdivo have failed in late-stage trials in that arena.
Because of that win in metastatic disease was “unambiguous,” Roche is “pretty bullish” about the new adjuvant liver cancer setting, Anderson said during Thursday's call. In the IMbrave050 trial, Roche is now testing the Tecentriq-Avastin combo as an adjuvant therapy. The primary goal will see whether the regimen can reduce the risk of disease recurrence or death compared with active surveillance.
Separately, another perhaps even more closely watched study, IMpower030, is testing Tecentriq plus chemotherapy in patients with resectable, early-stage NSCLC before surgery. Just in March, Opdivo became the first PD-1/L1 to enter the neoadjuvant NSCLC setting. Opdivo’s CheckMate-816 trial is slightly different from Tecentriq’s current IMpower030 trial in that the Opdivo study includes stage 1b to 3a disease, whereas Tecentriq’s covers stage 2 to 3b.
Meanwhile, Tecentriq currently boasts a landmark FDA approval for postsurgery adjuvant treatment for NSCLC with PD-L1 expression of at least 1%. That nod is limited to stage 2 to 3a because the showing in stage 1b disease was unconvincing.
The adjuvant NSCLC use is driving Tecentriq sales these days. In the second quarter, Tecentriq sales increased by 13% at constant currencies to 933 million Swiss francs, making it the fourth top-selling drug at Roche.
In the U.S., PD-L1 screening for early NSCLC is currently at 80%, and Tecentriq has grabbed 60% market share in the PD-L1-high population, Anderson said.
“The 13% growth isn’t all we’re capable of,” Anderson said. The PD-L1 inhibitor is recovering from some indication withdrawal or restriction in triple-negative breast cancer and bladder cancer, and it’s also experiencing sales decline Japan after a mandatory price cut earlier this year.
Tecentriq’s kidney cancer flop adds to a long list of negative news for Roche’s oncology department lately. Most notably, TIGIT inhibitor tiragolumab, a potential combination partner with Tecentriq, has disappointed in both small cell lung cancer and NSCLC.
The company’s oral SERD, giredestrant, missed the mark in a midphase breast cancer trial in April. And also in breast cancer, AstraZeneca and Daiichi Sankyo’s Enhertu in May entered second-line HER2-positive disease after an overwhelming trial win against Roche’s Kadcyla.
Those all come as Roche is trying to overcome a slate of patent cliffs. In the first six months of 2022, biosimilars to Avastin, Herceptin and Rituxan together eroded nearly 1 billion Swiss francs from the three old cancer blockbusters, and Roche still expects a full-year decline of 2.5 billion Swiss francs.
Overall, Roche’s pharma division generated 22.3 billion Swiss francs in sales, up 3% year over year. Multiple sclerosis drug Ocrevus and hemophilia therapy Hemlibra were among the main growth drivers.
The company also announced a leadership transition. CEO Severin Schwan will become chairman next March, handing the baton to diagnostics head Thomas Schinecker.