Investor Update

Basel, 01 June 2018

Roche to present data for TECENTRIQ (atezolizumab) from across its genitourinary and gastrointestinal cancer immunotherapy programme at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting

  • The data to be presented further demonstrate potential of TECENTRIQ and Avastin combination in renal cell carcinoma, a type of kidney cancer, and hepatocellular carcinoma, a type of liver cancer
  • Patient-Reported Outcomes (PRO) collected in the Phase III IMmotion151 study in renal cell carcinoma to be presented

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that data from across its genitourinary (GU) and gastrointestinal (GI) cancer immunotherapy development programme will be presented during the American Society of Clinical Oncology (ASCO) Annual Meeting from 1-5 June in Chicago, IL, United States. Data to be presented at ASCO 2018 demonstrate the potential of the combination of TECENTRIQ® (atezolizumab) and Avastin® (bevacizumab) in first-line advanced or metastatic renal cell carcinoma (mRCC) and hepatocellular carcinoma (mHCC), as well as show initial data for TECENTRIQ monotherapy as a neoadjuvant treatment in early stage urothelial carcinoma (UC).

“We are pleased to present positive Patient-Reported Outcomes data from the Phase III IMmotion151 study, which demonstrate the quality of life benefits that TECENTRIQ and Avastin potentially bring to people living with advanced kidney cancer,” said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. “We will also present promising early data for TECENTRIQ and Avastin in advanced or metastatic liver cancer, where there is a significant need for new therapies. Data from these two studies provide further evidence to support the potential of this unique combination across multiple settings.”

Patient-Reported Outcome (PRO) collected in the Phase III IMmotion151 study investigating the combination of TECENTRIQ and Avastin as a first-line treatment for mRCC, compared with a current standard of care sunitinib, were evaluated in the overall study population and show:

  • Patients receiving the combination reported a better health-related quality of life (HRQol) overall when compared with sunitinib. HRQol evaluates the overall impact of disease and treatment on patient’s quality of life in terms of disease related symptoms, treatment side effects and function/well-being
  • Patients receiving the combination reported lower impact of symptoms on day-to-day life, when compared with patients receiving sunitinib
  • The combination of TECENTRIQ and Avastin markedly increased the time before symptoms meaningfully impacted day-to-day life compared to sunitinib (median time to deterioration: 11.3 vs 4.3 months; HR=0.56; 95% CI: 0.46, 0.68)
  • Patients receiving the combination had milder and more stable symptom severity overall and a clinically meaningful reduction in the five most severe disease symptoms
  • Patients completed questionnaires on Days 1 and 22 of each 6-week cycle, at the end of treatment

Earlier this year, Roche announced that IMmotion151 met its co-primary endpoint of investigator-assessed progression-free survival (PFS) when comparing the TECENTRIQ and Avastin combination with sunitinib for people whose disease expressed the PD-L1 (programmed death-ligand 1) protein. The safety profile was consistent with previously reported data, with a discontinuation of the combination regimen only occurring in 5% of the patients and a lower rate of Grade 3-4 treatment-related adverse events with the TECENTRIQ and Avastin combination (40%) than with sunitinib alone (54%). 16% of patients required use of systemic steroids within 30 days of the onset of an immune-related AE.

Further data for TECENTRIQ and Avastin will be presented from an ongoing Phase Ib study evaluating the combination as a first-line treatment in untreated advanced, unresectable or metastatic HCC. In the safety evaluable population (n=43), 28% patients (n=12) experienced Grade 3-4 treatment-related adverse events and no treatment-related Grade 5 adverse events were observed. No new safety signals were identified beyond the established safety profiles for the individual medicines. After a median follow-up of 10.3 months, responses (investigator assessed per RECIST v1.1) were seen in 14 (61%) of 23 efficacy evaluable patients and regardless of disease etiology (cause), region (Asia or US), baseline alpha-fetoprotein levels or spread of tumour beyond the liver. Assessment by independent review facility (IRF) assessed per RECIST v1.1 revealed a response rate of 65% (15 out of 23 patients). Median progression free survival (PFS), duration of response (DOR), time to progression (TTP) and overall survival (OS) have not yet been reached after a median follow-up of 10.3 months; results will be presented at a future medical congress when updated data from an expanded cohort are available. A larger randomised Phase III study in untreated locally advanced or metastatic HCC, IMbrave150, evaluating the combination of TECENTRIQ and Avastin versus the standard of care sorafenib, is underway and recruiting patients.

In early stage bladder cancer, results from an interim analysis of a Phase II investigator-initiated study (ABACUS) evaluating neoadjuvant TECENTRIQ monotherapy in 68 evaluable patients with muscle invasive disease will also be presented. Topline results demonstrated a clinically meaningful pathological complete response (pCR) rate of 18 / 62 (29%). Of the pCR patients, 17% had pT3/4 disease at baseline. Treatment-related Grade 3-4 adverse events occurred in 12% of patients while Grade 3-4 surgical complications occurred in 31% of patients. The trial aims to test the efficacy of preoperative TECENTRIQ and includes extensive biomarker work on samples from these patients.

The results of the three studies will be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting on Sunday 3 June 2018.

About the IMmotion151 study

IMmotion151 is a Phase III multicentre, randomised, open-label study to evaluate the efficacy and safety of TECENTRIQ and Avastin versus sunitinib in people with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. It enrolled 915 people globally who were randomised 1:1 to receive TECENTRIQ and Avastin, or sunitinib alone.

People in the TECENTRIQ and Avastin arm received TECENTRIQ at a fixed dose of 1200 milligrams (mg) and Avastin at a dose of 15 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 3 weeks until loss of clinical benefit or unacceptable toxicity. People in the sunitinib arm received sunitinib 50 mg orally, once daily for 4 weeks followed by 2 weeks rest until loss of clinical benefit or unacceptable toxicity.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in people whose tumours expressed PD-L1 (expression ≥1 percent on immune cells [IC]), and OS in the overall study population (intention-to-treat, ITT). PD-L1 expression was prospectively assessed using an immunohistochemistry (IHC) test (SP142) developed by Roche Tissue Diagnostics. Secondary endpoints included OS in people whose tumours expressed PD-L1, PFS as determined by an Independent Review Facility (IRF) according to RECIST v1.1, investigator-assessed objective response rate (ORR) and duration of response (DOR), change from baseline in symptom interference and symptom severity as determined by M.D. Anderson Symptom Inventory (MDASI), and change from baseline in health-related quality of life as determined by European Quality of Life 5-Dimension (EQ-5D) Scores. PROs were evaluated as secondary and exploratory endpoints to document patient perspective on overall clinical benefit for each treatment.

About the Phase Ib study in HCC (NCT02715531)

This Phase Ib study evaluates the safety and clinical activity of the combination of TECENTRIQ and Avastin in people with untreated advanced, unresectable or metastatic HCC. Patients received TECENTRIQ (1200 mg) + Avastin (15 mg/kg) IV every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary objective was to assess the safety and tolerability as well as the efficacy of the combination. The primary efficacy endpoint is investigator-assessed objective response rate (ORR). Secondary efficacy endpoints include progression-free survival (PFS), duration of response (DOR) and time to progression (TTP) per RECIST v1.1; as well as overall survival (OS).

About IMbrave150

IMbrave150 is a Phase III, multicentre, randomised open-label study randomising approximately 480 patients with untreated advanced, unresectable or metastatic hepatocellular carcinoma 2:1 to receive TECENTRIQ in combination with Avastin or sorafenib. TECENTRIQ will be administered by IV, 1200mg on day 1 of each 21 day cycle and Avastin will be administered by IV, 15mg/kg on day 1 of each 21 day cycle. Sorafenib will be administered by mouth, 400mg twice per day, on days 1-21 of each 21 day cycle. Patients will receive the combination and the control arm until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints are overall survival and investigator-assessed objective response rate. Secondary endpoints include progression free survival (PFS), time to progression (TTP), duration of response (DOR) and independent review facility (IRF) assessed responses.

About the ABACUS study

ABACUS is an investigator-initiated, open-label, international, multicentre, phase II trial for patients with histologically confirmed (T2-T4a) transitional cell carcinoma of the bladder. The trial aims to test the efficacy of preoperative TECENTRIQ and includes extensive biomarker work on samples from these patients. Patients received two 3-weekly cycles of TECENTRIQ prior to cystectomy. Following cystectomy, patients were followed up for safety, survival, and disease data. Co-primary endpoints are (1) efficacy of atezolizumab prior to cystectomy assessed as pathological complete response rate and (2) immune parameters. Secondary endpoints include safety and efficacy based on anti-tumour effect by radiological response.

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.

TECENTRIQ is already approved in the European Union, United States and more than 70 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 combining TECENTRIQ and Avastin. The TECENTRIQ and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. 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 renal cell carcinoma

Kidney cancer remains one of the most common cancers in the world, accounting for over 140,000 deaths worldwide each year,1 with renal cell carcinoma (RCC) accounting for approximately 90% of all cases.2 Over 300,000 people are diagnosed with RCC every year and currently only about 1 in 10 people are alive beyond 5 years following diagnosis of metastatic disease.3

RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where our blood is filtered.4 Typically, RCC is a single tumour in one kidney but, in rare cases, there can be multiple tumours, which can occur in one or both kidneys.5

Despite recent progress in the field of kidney cancer, treatment options for people with the disease remains limited.

About hepatocellular carcinoma

HCC is the most common primary malignancy of the liver and has a very high fatality rate.6 Globally, it’s the fifth most common cancer in men and the seventh most common cancer among women, with over half a million new cases diagnosed annually.6 HCC develops predominantly in those patients with cirrhosis due to chronic hepatitis B or C,6 and typically presents at an advanced stage where there are limited treatment options.7

About urothelial carcinoma

Bladder cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 165,000 deaths globally each year. Men are three times more likely to suffer from bladder cancer, compared with women,8 and the disease is three times more common in developed countries than in less developed countries.9 There are three types of bladder cancer: transitional cell carcinoma (which begins in cells in the innermost tissue layer), squamous cell carcinoma (which begins in squamous cells) and adenocarcinoma (which begins in glandular cells in the lining of the bladder). Most cancers that form in the bladder are transitional cell carcinomas.10

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: https://www.roche.com/research_and_development/what_we_are_working_on/oncology/cancer-immunotherapy.htm 

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.
Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry nine years in a row by the Dow Jones Sustainability Indices (DJSI).
The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2017 employed about 94,000 people worldwide. In 2017, Roche invested CHF 10.4 billion in R&D and posted sales of CHF 53.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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References:

  1. World Health Organization. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide. Available at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx Last accessed May 2018.
  2. American Cancer Society. What is kidney cancer? Available at: http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-what-is-kidney-cancer Last accessed May 2018.
  3. SEER. Stat Fact Sheets: Kidney and Renal Pelvis Cancer. Available at: https://seer.cancer.gov/statfacts/html/kidrp.html Last accessed May 2018.
  4. Cancer.gov. Renal Cell Cancer Treatment (PDQ®): Patient Version. Available at: https://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq Last accessed May 2018.
  5. Rini, BI et al. Vascular Endothelial Growth Factor Targeted Therapy in Renal Cell Carcinoma: Current Status and Future Directions. Clin Cancer Res. 2007; 13: 1098-106.
  6. Mittal, S et al. Epidemiology of HCC: Consider the Population. J Clin Gastroenterol. 2013; 47(0): S2-S6.
  7. Raza A and Sood GK. Hepatocellular carcinoma review: Current treatment, and evidence-based medicine. World J Gastroenterol.2014; 20(15): 4115-4127.
  8. Patient. Bladder Cancer. Available at: http://patient.info/health/bladder-cancer-leaflet Last accessed May 2018.
  9. World Cancer Research Fund International. Comparing more & less developed countries. Available from: http://www.wcrf.org/int/cancer-facts-figures/comparing-more-less-developed-countries Last accessed May 2018.
  10. Cancer.gov. Bladder Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)–Patient Version. Available at: https://www.cancer.gov/types/bladder/patient/about-bladder-cancer-pdq Last accessed May 2018.