Last month, Roche’s Tecentriq found a surprising failure when used in tandem with paclitaxel chemotherapy in triple negative breast cancer (TNBC). The FDA has taken notice, issuing a warning that could cause problems for a conditional PD-L1 nod.

Tuesday, the FDA alert the public that the Tecentriq-paclitaxel combo did not work in a previously untreated locally advanced or metastatic TNBC clinical trial and warned doctors not to use it.

The point is that Tecentriq already has a approval at TNBC, which he won in March 2019 – and it’s that nod that could be in jeopardy. “Continued approval … may depend on the proven benefit of the treatment in additional trials,” the FDA said.

Tecentriq’s go-ahead, limited to cases expressing PD-L1, is for a combination with Celgene’s Abraxane, or protein-bound paclitaxel, a formulation where paclitaxel is bound to albumin nanoparticles in a delivery mechanism that helps the drug to concentrate in the tumor areas.

This conditional approval was based on data from the Phase 3 IMpassion130 study, which showed that Tecentriq-Abraxane reduced the risk of worsening disease or death by 40% compared to Abraxane alone in patients with TNBC. PD-L1 positive and not previously treated.

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However, in the phase 3 IMpassion131 trial, adding Tecentriq to paclitaxel did not stop tumor progression in newly diagnosed PD-L1-positive patients. To make matters worse, the interim results even favored solo paclitaxel in terms of prolonging life, although Roche said the data was inconclusive.

Based on the latest trial failure, the agency said it will review the results and announce any changes to Tecentriq’s prescribing information.

In a statement, a spokesperson for Roche’s Genentech declined to say whether the failure of IMpassion131 could affect Tecentriq’s approved use of TNBC, saying only that the company is in active discussions with the FDA.

Of course, IMpassion131 might not threaten the existing indication after all. First, compared to conventional paclitaxel, Abraxane is linked to preferential uptake in cancer cells and, therefore, potentially offers a better anti-tumor effect due to its unique delivery technology.

Additionally, IO drugs have already failed confirmatory trials, but so far none have led the FDA to end an approval. Tecentriq itself in 2017 flopped a phase 3 trial in previously untreated bladder cancer, but still needs to continue to progress based on phase 2 tumor response data. In June, rival drug PD-1 from Merck & Co., Keytruda, alone or in combination with chemotherapy, lack to significantly ward off bladder tumors compared to chemotherapy. But this drug may not lose its conditional approval either; there’s no word from the FDA yet.