Clinical Trials

Date: 2017-02-19

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 2017 Genitourinary Cancers Symposium

Company: Roche (Switzerland)

Product: Tecentriq® (atezolizumab) and Avastin® (bevacizumab)

Action mechanism:

immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. Anti-PDL1 antibody MPDL3280A is an investigational monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer.  

In February 2015, MPDL3280A received Breakthrough Therapy from the FDA for the treatment of people whose NSCLC expresses PD-L1 and who progressed during or after standard treatments (e.g., platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). Roche’s Biologics Licence Application (BLA) for NSCLC was granted Priority Review with an action date of 19 October 2016.

Bevacizumab is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor), the key driver of tumor angiogenesis.

Disease: renal cell carcinoma

Therapeutic area: Cancer - Oncology

Country: Czech Republic, France, Germany, Italy, Poland, Romania, Spain, UK, USA

Trial details:

IMmotion150 is a global, multicentre, open-label, randomised Phase II study that was designed to evaluate the efficacy and safety of Tecentriq® plus Avastin (Arm A), Tecentriq® alone (Arm B) or sunitinib alone (Arm C) in 305 patients with previously untreated, locally advanced or metastatic RCC. People in Arm A received Tecentriq® administered intravenously at 1200 mg every 3 weeks (6-week cycles) plus Avastin intravenously at 15 mg until disease progression or lack of clinical benefit. People in Arm B received Tecentriq® alone (until disease progression or lack of clinical benefit), and people in Arm C received sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks rest until disease progression.Patients enrolled into arm B (atezolizumab alone) in Europe (including France, Italy, the United Kingdom, Romania, Spain, Germany, the Czech Republic and Poland) are not eligible to cross over into arm A to receive combination treatment with atezolizumab and bevacizumab following disease progression, per local regulatory requirement.

The co-primary endpoints were PFS per RECIST v.1.1 via Independent Review Facility (IRF) assessment in all randomised patients (ITT population) and in the PD-L1 selected (IC1/2/3) subgroup. PD-L1 expression was assessed on tumour-infiltrating immune cells (IC) with an investigational immunohistochemistry (IHC) test based on the SP142 antibody being developed by Roche Tissue Diagnostics. Secondary endpoints included IRF-assessed overall response rate (ORR) and duration of response (DoR), investigator-assessed PFS, ORR, DoR and safety, and overall survival (OS). (NCT01984242)

Latest news:

* On February 18, 2017, Roche announced results from the Phase II IMmotion150 study that compared Tecentriq® (atezolizumab) plus Avastin® (bevacizumab) and Tecentriq® monotherapy to sunitinib alone in people with previously untreated, locally advanced or metastatic renal cell carcinoma (mRCC). These results were presented at the 2017 Genitourinary Cancers Symposium taking place from February 16-18 in Florida, USA. IMmotion150 was designed to inform further clinical development of this combination and these study results reinforce the potential of this combination in this setting.

The study showed that people whose disease expressed PD-L1 (programmed death-ligand 1) and were treated with Tecentriq® plus Avastin had a 36 percent reduction in the risk of their disease worsening or death compared to people treated with sunitinib alone (median progression-free survival [mPFS]: 14.7 vs. 7.8 months; HR= 0.64; 95% CI 0.38, 1.08). No PFS advantage was observed compared to sunitinib in the intention-to-treat [ITT] population (mPFS: 11.7 vs. 8.4 months; HR = 1.00; 95% CI 0.69, 1.45). Median Duration of Response (DoR) has not yet been reached after 20.7 months of follow-up across treatment arms. Adverse events in the Tecentriq® plus Avastin arm were consistent with those observed in previous studies of each medicine. A summary of the efficacy data from Arms A, B and C of the IMmotion150 study is included below.

IMmotion150 was designed with planned crossover. Over three quarters (78 percent) of sunitinib patients (Arm C) who progressed subsequently received Tecentriq® plus Avastin (Arm A) OS results were immature at time of analysis with only 35 percent of events having occurred.
Safety in the Tecentriq® plus Avasti®n arm appeared consistent with the known safety profile of the individual medicines. No new safety signals were identified. Frequency of all-grade treatment-related adverse events was similar between arms. The most common AE’s occurring in more than 20% of patients receiving Tecentriq® plus Avastin® and with a greater than 5% increase when compared to sunitinib included: arthralgia (38%), proteinuria (36%), epistaxis (28%), and pruritus (22%). Frequency of grade 3-4 AEs regardless of relationship to treatment were similar between patients treated with Tecentriq® plus Avastin® (63%) and sunitinib (69%). Treatment-related grade 3-4 events reported in 40% of Tecentriq® plus Avastin® treated patients and 57% of sunitinib treated patients. One person who was treated with Tecentriq® plus Avastin® experienced intracranial haemorrhage that led to death. Fifteen of 101 patients (15%) treated with Tecentriq® plus Avastin® discontinued treatment for adverse events.

Is general: Yes