Tecentriq runs out of luck in triple-negative breast cancer

Roche puts on a brave face as its anti-PD-L1 drug fails yet another TNBC study, this time in the adjuvant setting.

Roche’s historic strength in breast cancer once looked likely to extend to triple-negative disease courtesy of Tecentriq, but now the PD-L1 MAb is drinking in the last-chance saloon.

Today’s quiet discontinuation of Impassion-030 in adjuvant TNBC, a major study as Roche tries to push into perioperative settings, marks the latest in a list of failures and disappointments. It comes as new management tries desperately to improve the Swiss group’s oncology fortunes, which had recently been brightened by Tecentriq’s surprising success in adjuvant liver cancer.

In TNBC (triple-negative breast cancer), however, the latest setback comes after the perioperative NeoTRIPaPDL1 trial failed in December 2019. Tecentriq plus chemo did once have accelerated approval for first-line TNBC, thanks to Impassion-130, but that was rescinded when the confirmatory Impassion-131 study drew a blank; that was followed by the failure of a first-line ipatasertib combo in Ipatunity-170.


On its first-quarter investor call today Roche said Impassion-030 had been discontinued after a data-monitoring committee conducted a futility analysis and ruled that the chemo combo trial was unlikely to meet its primary endpoint of invasive disease-free survival versus chemo alone.

In perioperative TNBC Roche had already lost ground to Merck & Co, which succeeded in getting Keytruda plus chemo fully approved on the basis of the controversially designed Keynote-522 trial. The trial had also supported the Merck MAb’s full first-line approval in ≥10% PD-L1 expressers.

Roche did appear to score in the neoadjuvant Impassion-031 trial, but that was on the basis of pathological complete response, which is not generally an approvable endpoint. This fact was confirmed when Roche pulled an EU filing for this use and Impassion-031 failed to show a benefit on event-free survival.

Tecentriq in triple-negative breast cancer
Study Design Primary endpoint(s) Result
Impassion-031 Abraxane combo, vs Abraxane pCR in PD-L1+ and all-comers Positive for pCR, negative for EFS (secondary endpoint); EU filing withdrawn
Neoadjuvant + adjuvant
NeoTRIPaPDL1* Abraxane combo, vs Abraxane EFS Failed in Dec 2019
MO39875* Chemo combo, vs chemo pCR & EFS Ends in Dec 2023
Impassion-030 Chemo combo, vs chemo iDFS Failed in Q1 2023
Impassion-130 Abraxane combo, vs Abraxane OS & PFS in PD-L1+ and all-comers Approved in ≥1% PD-L1, but withdrawn in Aug 2021 after Impassion-131 failed
Impassion-131 Paclitaxel combo, vs paclitaxel PFS in PD-L1+ and all-comers Upsized by 11%, failed in Oct 2020
Impassion-132 Chemo combo, vs chemo OS in PD-L1+ and all-comers Upsized by 63%, completion delayed from Jul 2019 to Jun 2023
Ipatunity-170 Ipatasertib + paclitaxel +/- Tecentriq vs paclitaxel +/- Tecentriq PFS & OS in PD-L1+ & PD-L1- Failed in Feb 2021
Note: *academia-sponsored study. pCR=pathological complete response; EFS=event-free survival; iDFS=invasive disease-free survival. Source: clinicaltrials.gov & company presentation.

Other pipeline changes revealed by Roche today included discontinuation of the geographic atrophy project RG6312, though the group has a couple of other irons in the fire here.

In oncology Roche played up its Kras G12C inhibitor RG6330, which now carries the INN divarasib and is in phase 3. And it confirmed that the hotly awaited Skyscraper-01 trial of Tecentriq plus the Tigit MAb tiragolumab had not hit for overall survival at an interim analysis, and was thus continuing to final readout in the third quarter.

Despite this Roche’s recently appointed head of pharma, Teresa Graham, said the group continued to be interested in the Tigit pathway, and was considering starting new phase 3 trials. The Tigit story is “far from fully written”, she told analysts.

And she defended Tecentriq, insisting that Impassion-030’s failure did not affect any other ongoing TNBC trials; these include MO39875 in perioperative disease and the upsized first-line Impassion-132 chemo combo study, both due to end this year. True, Tecentriq cannot be entirely written off in TNBC, but given the numerous setbacks this looks like an optimistic take.

Roche stock slipped slightly on today’s first-quarter figures, and the latest pipeline setbacks mean that Graham and the group’s new chief executive, Thomas Schinecker, have it all to do.

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