Roche's Tecentriq Fails in Two Combination Trials for Prostate Cancer and Lymphoma

Compiled by Fan Dongdong

Recently, Roche announced the results of several Tecentriq combination trials during the American Association for Cancer Research (AACR) Annual Meeting, including Tecentriq combined with Xtandi for the treatment of prostate cancer and Tecentriq combined with Yescarta for the treatment of lymphoma. Unfortunately, neither trial yielded positive results.

Tecentriq+Xtandi

Xtandi, a blockbuster drug for prostate cancer treatment under Astellas Pharma, was combined with Roche’s tumor immunotherapy Tecentriq in hopes of further improving therapeutic outcomes for prostate cancer; however, the results were unsatisfactory.

According to the Phase 3 study results released by Roche, the data showed that the median overall survival for patients treated with Tecentriq in combination with Xtandi was 15.2 months, compared to 16.6 months for those treated with Xtandi alone. In other words, the addition of Tecentriq resulted in a decrease in median overall survival.

Worse still, subgroup analyses of the trial also failed to demonstrate any benefit from the combination of Tecentriq and Xtandi, including in patients with higher levels of the PD-L1 biomarker. Previously, this type of biomarker had emerged as a key predictor of treatment success with Tecentriq-like therapies in certain tumor types.

A spokesperson for Roche’s Genentech stated in an email, “We are reviewing the relevant trial data and will leverage our expertise to inform future research.” He added that although the trial was discontinued last year due to futility, “research into relevant biomarkers is still ongoing.”

Despite the tremendous success of PD-(L)1 checkpoint inhibitors in other areas, this class of drugs has not yet made significant inroads into the field of prostate cancer. In recent years, Xtandi and Johnson & Johnson’s Zytiga have garnered considerable attention in this domain. Recently, Erleada, a successor to Zytiga, along with PARP inhibitors Lynparza from AstraZeneca and Merck, and Clovis’s Rubraca, have begun to enter this indication, suggesting that Roche’s offensive in this area appears to have encountered temporary setbacks.

Tecentriq+Yescarta

Tecentriq was also combined with Gilead’s Yescarta in another study aimed at evaluating whether adding CAR-T therapy to PD-(L)1 inhibitors could improve prognosis in lymphoma patients. However, after small-scale early-stage studies, there is still no evidence demonstrating efficacy benefits from the combination therapy.

Roche’s Phase 1/2 study results showed that the combination of Tecentriq and Yescarta demonstrated a manageable safety profile in patients with diffuse large B-cell lymphoma (DLBCL); however, efficacy outcomes and CAR-T cell levels were similar to those observed in patients treated with Yescarta alone.

During the 10.2-month treatment period, 46% of patients receiving dual therapy achieved complete tumor disappearance. However, the tumor elimination rate in the Yescarta monotherapy group reached 58%, indicating that current trial results do not demonstrate that combination therapy enhances efficacy.

Although neither of the two combination therapy studies yielded the expected positive results, external analysts believe that Roche will not slow its pace in immuno-oncology. Roche is striving to establish a foothold in immuno-oncology to compete with Keytruda and Opdivo.

References:

1、Adding Roche's Tecentriq to Xtandi doesn't extend lives in prostate cancer—even in subgroups

2、Roche's Tecentriq doesn't amp up Gilead's Yescarta in lymphoma, early study says