An immune checkpoint inhibitor made by Swiss drugmaker Roche has become the third in less than a month to experience a setback in its development.

In a letter to regulators last month just published on the European Medicines Agency website, the Basel, Switzerland-based drugmaker said it was withdrawing its application for the approval of the PD-L1 inhibitor Tecentriq (atezolizumab) combined with Avastin (bevacizumab) for first-line, unresectable, locally advanced or metastatic renal cell carcinoma. The letter, dated Oct. 22, stated that the decision was based on results from the Phase III IMmotion151 study indicating they were not sufficient to support the indication. However, the company said it would continue the study to the next analysis for overall survival.

Tecentriq has Food and Drug Administration approval for second-line treatment of urothelial carcinoma and non-small cell lung cancer. The other two PD-L1 inhibitors to be hit with bad news – Pfizer and Germany-based Merck KGaA’s Bavencio (avelumab) and AstraZeneca’s Imfinzi (durvalumab) – respectively have accelerated FDA approval for the rare skin cancer Merkel cell carcinoma and second-line urothelial carcinoma.

On Monday, Pfizer and Merck KGaA said that the Phase III JAVELIN Ovarian 200 study of their PD-L1 inhibitor, Bavencio, failed to show improvement in overall survival or progression-free survival among patients with platinum chemotherapy-resistant or refractory ovarian cancer. That was whether Bavencio was given alone or combined with the chemotherapy drug pegylated liposomal doxorubicin.

And last Friday, AstraZeneca announced that a Phase III study of its PD-L1 inhibitor, Imfinzi, had failed to show a statistically significant benefit in survival among patients with newly diagnosed non-small cell lung cancer. What’s more, the company said, the combination of Imfinzi with its investigational CTLA-4 inhibitor, tremelimumab, did even worse than Imfinzi by itself, with a hazard ratio of 0.85, compared with 0.76 for the standalone drug. The negative result effectively takes the single drug and the combination out of the running as a potential competitor in first-line NSCLC against Merck & Co.’s PD-1 inhibitor Keytruda (pembrolizumab), the only drug in the class currently approved for the disease.

Keytruda also has approval for several other indications, as does the other PD-1 inhibitor, Bristol-Myers Squibb’s Opdivo (nivolumab).

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