Tecentriq (atezolizumab) is an approved cancer immunotherapy developed by Genentech for the treatment of lung, breast, and urothelial cancers. It is also being investigated in several types of other cancers, like bladder and blood cancers, such as lymphoma.

How does Tecentriq work?

Tecentriq is a cancer immunotherapy, which is a type of treatment that uses the body’s own immune system to fight cancer. It is a monoclonal antibody that has been designed to bind a protein called programmed death-ligand 1 (PD-L1).

PD-L1 is normally found on the surface of healthy cells, and functions by binding to its receptor PD-1 found on the surface of immune cells called T-cells. This binding sends a signal to the T-cells to stop fighting, ensuring that normal cells are not mistakenly attacked by the immune system. Cancer cells can also produce PD-L1 and evade detection by the immune system.

When Tecentriq binds to PD-L1, which is produced by cancer cells at much higher levels than normal cells, it restores the normal function of the immune system, ensuring that T-cells recognize, attack, and kill cancer cells.

Tecentriq in clinical trials

The potential benefits of intravenous (IV) injections of Tecentriq in treating lymphoma are being investigated in several clinical trials.

Genentech began a collaboration with Kite Pharma in March 2016 to evaluate the safety and efficacy of Tecentriq in combination with Yescarta (KTE C19), another type of immunotherapy called CAR T-cell therapy, in patients with aggressive non-Hodgkin’s lymphoma. The Phase 1/2 trial (NCT02926833) called ZUMA-6 started in October 2016 and has two distinct phases: in Phase 1b, the safety of the combination will be assessed by measuring the incidence of dose-limiting adverse events; in Phase 2, the safety and effectiveness of the combination will be assessed by measuring the overall response rate. The results of the first phase in 12 patients with diffuse large B-cell lymphoma (DLBCL) were published in March 2019. They showed that treatment with Yescarta plus Tecentriq was well tolerated and showed a two-fold increase in CAR T cell expansion compared with Yescarta alone. Based on these results, the second phase of the study was initiated and is currently underway.

A multicenter Phase 1b study (NCT02220842) evaluated Tecentriq in combination with Gazyva (obinutuzumab) or tazemetostat in patients with follicular lymphoma (FL) and DLBCL.

Results from the trial, published in the scientific journal Blood, showed that the combination was well tolerated and showed promising activity in patients who had gone through several treatments by the time they received the combined treatment. Five patients were evaluated after four cycles (three months) of therapy and showed two partial responses (up to 68.6% of tumor reduction), two stable diseases, and one progressive disease. Updated data were presented in June 2017 at the 14th International Conference on Malignant Lymphoma and subsequently published in the journal Hematological Oncology, confirming previous results, with an overall response rate of 57% in patients with FL and 16% in those with DLBCL. The most common severe adverse effects were pain, anemia, and neutropenia. A total of 13 patients interrupted treatment due to side effects.

Another Phase 2 study (NCT03463057) in patients with DLBCL is investigating Tecentriq on its own. The study is currently recruiting an estimated 114 participants in Belgium and the Netherlands. Participants will have first completed 18 cycles of rituximab, cyclophosphamide, hydroxo-doxorubicin, vincristine, and prednisone (R-CHOP) treatment and will then be given 18 cycles of Tecentriq followed by 12 months of observation. The estimated completion date of the study is April 2025.

A Phase 1b/2 clinical trial (NCT02631577) was designed to assess the safety and effectiveness of Tecentriq in combination with Gazyva plus Revlimid (lenalidomide) in patients with FL. However, the trial was placed on partial hold by regulatory authorities in September 2017 due to safety concerns. The hold was lifted in December 2017, and the primary analysis of the data was done in October 2018. It showed that the combination treatment had similar safety and efficacy to the individual drugs. Final results were posted for 38 patients on the clinical trials website in December 2019 but no final review of the results has been released yet.

A Phase 2 clinical trial (NCT03120676) started in April 2017 to evaluate Tecentriq in patients with Hodgkin’s lymphoma whose disease returned after a period of improvement or became resistant to treatment. A similar Phase 2 trial (NCT03465891) in FL was also being investigated. Both studies were terminated, however, due to lack of funding and lack of patient recruitment.

Another Phase 2 study (NCT03276468) is currently recruiting participants in several locations in France to investigate the anti-lymphoma activity of Tecentriq combined with Venclexta (venetoclax) and Gazyva in up to 138 lymphoma patients.

A Phase 2 clinical trial (NCT03357224), called PARCT, will investigate Tecentriq in patients with cutaneous T-cell lymphomas, specifically mycosis fungoides, and Sezary syndrome. The study is currently recruiting an estimated 29 patients to receive treatment for up to one year. Patients will be monitored for up to five years after receiving treatment and any changes in their disease during this period of time will be observed. The study is expected to conclude in 2025.

Other early phase clinical trials that are currently ongoing to investigate the effectiveness and safety of Tecentriq combined with other treatments in several types of lymphomas are NCT02500407, NCT02596971, NCT03321643, NCT02846623, NCT03892525, NCT03533283, NCT04167137, NCT03422523, NCT03321643, NCT02594384, NCT03841110.

 

Last updated: Feb. 6, 2020

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.