Roche secures a front-line liver cancer label, but rival data at Asco show that the competition isn’t resting on its laurels.
Today’s US approval for Roche’s Tecentriq/Avastin combo, backed by overall survival in the Imbrave-150 trial, marks a first for immunotherapy in first-line liver cancer.
It also boosts Roche’s Avastin lifecycle strategy, as well as enabling the group to leapfrog Merck & Co and Bristol-Myers Squibb, whose Keytruda and Opdivo both carry liver cancer labels but only in the second-line setting. Bristol failed in Checkmate-459, a front-line Opdivo monotherapy study, however Roche’s lead might not last long.
Judging by data presented at Asco over the weekend, front-line liver cancer competition could be around the corner. The next threat could come from Astrazeneca, which hopes to report the findings of the first-line Himalaya study later this year.
This tests Imfinzi monotherapy, or in two combinations with the anti-CTLA-4 agent tremelimumab, against Nexavar; the primary outcome is overall survival, though it is not clear how the statistical powering is being split across the trial’s various cohorts.
At Asco Astra provided a way of handicapping Himalaya, courtesy of a phase II trial called Study 22. This enrolled a mixture of first and second-line subjects, and though it effectively had no control cohort it did provide backing of sorts for the Imfinzi/tremelimumab combo.
It also boosts Roche’s Avastin lifecycle strategy, as well as enabling the group to leapfrog Merck & Co and Bristol-Myers Squibb, whose Keytruda and Opdivo both carry liver cancer labels but only in the second-line setting. Bristol failed in Checkmate-459, a front-line Opdivo monotherapy study, however Roche’s lead might not last long.
Judging by data presented at Asco over the weekend, front-line liver cancer competition could be around the corner. The next threat could come from Astrazeneca, which hopes to report the findings of the first-line Himalaya study later this year.
This tests Imfinzi monotherapy, or in two combinations with the anti-CTLA-4 agent tremelimumab, against Nexavar; the primary outcome is overall survival, though it is not clear how the statistical powering is being split across the trial’s various cohorts.
At Asco Astra provided a way of handicapping Himalaya, courtesy of a phase II trial called Study 22. This enrolled a mixture of first and second-line subjects, and though it effectively had no control cohort it did provide backing of sorts for the Imfinzi/tremelimumab combo.
Overall survival in Study 22. T300+D = 300mg tremelimumab + Imfinzi. Source: Dr Katie Kelley & Asco.
This fact alone puts study 22 in a rare category of trials in which tremelimumab has not been a flop.
The cohorts tested in the study were two regimens of the combo, as well
as Imfinzi or tremelimumab as monotherapies, all after a limited run-in
period on the combo.
The highlight was that the best median overall survival, 18.7 months, was seen in patients given Imfinzi plus 300mg tremelimumab – the same regimen that is being tested in one of the arms of Himalaya.
Curiously, tremelimumab monotherapy yielded the second-best mOS figure, 15.1 months, but the baseline characteristics were imbalanced: only 44% of treme monotherapy subjects were second-line, versus 57% of those on the combo. The presenters also said study 22 showed remissions regardless of subjects’ PD-L1 status.
For its part, Merck is relying on Eisai’s Lenvima as the other half of its Keytruda combination in front-line liver cancer; its pivotal Leap-002 study of this approach compared with Lenvima monotherapy reads out in 2022.
The highlight was that the best median overall survival, 18.7 months, was seen in patients given Imfinzi plus 300mg tremelimumab – the same regimen that is being tested in one of the arms of Himalaya.
Curiously, tremelimumab monotherapy yielded the second-best mOS figure, 15.1 months, but the baseline characteristics were imbalanced: only 44% of treme monotherapy subjects were second-line, versus 57% of those on the combo. The presenters also said study 22 showed remissions regardless of subjects’ PD-L1 status.
For its part, Merck is relying on Eisai’s Lenvima as the other half of its Keytruda combination in front-line liver cancer; its pivotal Leap-002 study of this approach compared with Lenvima monotherapy reads out in 2022.
Remissions in Keynote-524, per Recist 1.1. Source: Dr Andrew Zhu & Asco.
At Asco Merck presented a poster on Keynote-524, a small uncontrolled
trial of Keytruda plus Lenvima. This yielded 22.0 months of mOS, and 36
of the 100 subjects experienced disease remission. Though this was only
a phase I trial it effectively represented the front-line setting, as
subjects could not have received prior systemic therapy.
The one caveat for Merck is that its second-line label, backed by an accelerated approval, looks questionable after last year’s failure of the confirmatory phase III trial Keynote-240. Roche therefore has a lot going for its Avastin combo, but it must make the most of its window of opportunity.
https://www.evaluate.com/vantage/articles/events/conferences/asco-2020-after-tecentriqs-liver-win-spotlight-falls-merck-and
The one caveat for Merck is that its second-line label, backed by an accelerated approval, looks questionable after last year’s failure of the confirmatory phase III trial Keynote-240. Roche therefore has a lot going for its Avastin combo, but it must make the most of its window of opportunity.
https://www.evaluate.com/vantage/articles/events/conferences/asco-2020-after-tecentriqs-liver-win-spotlight-falls-merck-and
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