Positive fase III-resultater for kombinasjonsbehandling med Roches Tecentriq® ▼ og Avastin for lungekreft

Oslo 7. desember 2017: Roche kunngjorde i dag resultatene fra fase III-studien IMpower150 som viste at kombinasjonsbehandling med immunterapien Tecentriq (atezolizumab) og Avastin (bevacizumab), i tillegg til kjemoterapi, ga en statistisk signifikant redusert risiko for sykdomsforverring eller død med 38 prosent sammenlignet med Avastin og kjemoterapi.

Studien ble gjort på 1202 pasienter med tidligere ubehandlet, avansert, ikke-småcellet lungekreft (NSCLC) og er den første positive fase III-studien for kombinasjonsbehandling med immunterapi i denne settingen.

Etter 12 måneder var det dobbelt så mange pasienter i Tecentriq og Avastin pluss kjemoterapi armen som ikke hadde hatt sykdomsforverring eller dødsfall, sammenlignet med pasienter i Avastin pluss kjemoterapi armen (37 prosent versus 18 prosent). En endelig analyse av totaloverlevelsen vil bli utført i første halvdel av 2018.

▼Dette legemidlet er underlagt særlig overvåking for å oppdage ny sikkerhetsinformasjon så raskt som mulig. Du kan bidra ved å melde enhver mistenkt bivirkning. Dette gjøres via meldeskjema som finnes på nettsiden til Statens legemiddelverk: www.legemiddelverket.no/meldeskjema.

Les Roches internasjonale pressemelding for nærmere informasjon:

Phase III IMpower150 study showed Tecentriq (atezolizumab) and Avastin (bevacizumab) plus chemotherapy reduced the risk of disease worsening or death by 38 percent for people with a type of advanced lung cancer

• First Phase III combination trial of a cancer immunotherapy to show improvement in progression-free survival as an initial treatment in advanced non-squamous non-small-cell lung cancer (NSCLC)

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from the positive, pivotal Phase III IMpower150 study of Tecentriq® (atezolizumab) and Avastin® (bevacizumab) plus chemotherapy (carboplatin and paclitaxel) in people with previously untreated advanced non-squamous non-small cell lung cancer (NSCLC). The study showed that people who received Tecentriq and Avastin plus chemotherapy had a 38 percent reduced risk of their disease worsening or death (progression-free survival, PFS) compared with those who received Avastin plus chemotherapy (hazard ratio [HR]=0.62; p<0.0001 95 % CI: 0.52-0.74; median PFS = 8.3 vs. 6.8 months). Importantly, a doubling of the 12-month landmark PFS rate was observed with the combination of Tecentriq and Avastin plus chemotherapy (37 percent) compared to Avastin plus chemotherapy (18 percent). The rate of tumour shrinkage (overall response rate, ORR), a secondary endpoint in the study, was higher in people treated with Tecentriq and Avastin plus chemotherapy compared with Avastin plus chemotherapy (64 percent vs. 48 percent). The safety profile of the Tecentriq and Avastin plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.

The analysis of the co-primary PFS endpoint in IMpower150 was assessed in two populations: all randomised people without an ALK* or EGFR** genetic mutation (intention-to-treat wild-type, ITT-WT) and in a subgroup of people who had a specific biomarker (T-effector “Teff” gene signature expression Teff WT). IMpower150 met its PFS co-primary endpoint per study protocol for both populations assessed. In the Teff-WT population, the combination of Tecentriq and Avastin plus chemotherapy reduced the risk of disease worsening or death by 49 percent compared to Avastin plus chemotherapy (HR=0.51; p<0.0001 95% CI: 0.38-0.68; median PFS = 11.3 vs 6.8 months).

“This Tecentriq study is the first positive Phase III combination trial that showed a cancer immunotherapy reduced the risk of the disease getting worse when used as an initial treatment in a broad group of people with advanced non-squamous NSCLC,” Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “The IMpower150 study represents an important advance in lung cancer treatment, and we will submit these results to regulatory authorities around the world to potentially bring a new standard of care to people living with this disease as soon as possible.”

The late-breaking IMpower150 data will be presented at the European Society of Medical Oncology (ESMO) Immuno Oncology Congress (Abstract #LBA1_PR) on Thursday, 7 December 6.15 pm. Central European Time (CET) and are also part of the official press programme. Early results from the co-primary endpoint of overall survival (OS) are encouraging. While they are not yet fully mature, these preliminary OS results will be presented at the ESMO IO congress. The next analysis of survival is expected in the first half of 2018.

About the IMpower150 study

IMpower150 is a multicentre, open-label, randomised, controlled Phase III study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV or recurrent metastatic non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease. It enrolled 1,202 people of which those with ALK and EGFR mutations were excluded from the primary ITT analysis. People were randomised (1:1:1) to receive:

• Tecentriq plus carboplatin and paclitaxel (Arm A), or
• Tecentriq and Avastin plus carboplatin and paclitaxel (Arm B), or
• Avastin plus carboplatin and paclitaxel (Arm C, control arm).

During the treatment-induction phase, people in Arm A received Tecentriq administered intravenously at 1200 mg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. Following the induction phase, people received maintenance treatment with Tecentriq (1200 mg every 3 weeks) until loss of clinical benefit or disease progression.
Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet. IMpower150 was designed to formally compare Tecentriq plus chemotherapy (Arm A) versus Avastin plus chemotherapy (Arm C), only if Tecentriq and Avastin plus chemotherapy (Arm B) is shown to improve OS in the ITT-WT population compared to Avastin plus chemotherapy (Arm C). These OS results are expected in the first half of 2018.

People in Arm B received induction treatment with Tecentriq (1200 mg) and Avastin administered intravenously at 15 mg/kg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. People then received maintenance treatment with the Tecentriq Avastin regimen until disease progression (Avastin) or loss of clinical benefit/disease progression (Tecentriq).

People in Arm C received induction treatment with Avastin administered intravenously at 15 mg/kg plus intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. This was followed by maintenance treatment with Avastin alone until disease progression.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1), and OS.

A summary of the IMpower150 Arm B vs Arm C PFS and ORR results are included below; additional data, including preliminary OS results and Arm A vs Arm C PFS will be presented as part of the Late-Breaking Abstract presentation.

The safety profile of Tecentriq and Avastin plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events related to treatment were observed in 25.4 percent of people who received Tecentriq and Avastin plus chemotherapy compared to 19.3 percent of those who received Avastin plus chemotherapy.

About NSCLC

Despite recent advances in the treatment of NSCLC, there is still a need for new treatment options. Lung cancer is the leading cause of cancer death globally¹. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.² Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.²

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About the Tecentriq (atezolizumab) and Avastin (bevacizumab) combination

There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers, including first-line advanced NSCLC. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Roche in cancer immunotherapy

For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.
To learn more about the Roche approach to cancer immunotherapy please follow this link.