Phase III IMmotion151 Study Showed Genentech’s TECENTRIQ (Atezolizumab) and Avastin (Bevacizumab) Reduced the Risk of Disease Worsening or Death by 26 Percent in Certain People with Advanced Kidney Cancer

-- TECENTRIQ and Avastin met co-primary endpoint of investigator-assessed progression-free survival (PFS) compared with sunitinib for people whose disease expressed PD-L1 --
-- IMmotion151 is the second Phase III study to show positive PFS results for a treatment regimen including TECENTRIQ plus Avastin --
-- Data will be discussed with global health authorities, including the U.S. Food and Drug Administration (FDA) –

SOUTH SAN FRANCISCO, CA, USA I February 5, 2018 I Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced results from the positive Phase III IMmotion151 study of TECENTRIQ® (atezolizumab) and Avastin® (bevacizumab) as a first-line treatment for advanced or metastatic renal cell carcinoma (mRCC). The study met its co-primary endpoint of investigator-assessed progression-free survival (PFS) in people whose disease expressed the PD-L1 (programmed death-ligand 1: expression ≥ 1 percent) protein. Those who received TECENTRIQ plus Avastin had a 26-percent reduced risk of disease worsening or death (PFS) compared to people treated with sunitinib (median PFS [mPFS]: 11.2 vs. 7.7 months; HR=0.74; 95 percent CI 0.57, 0.96; p=0.02). Initial observations from the co-primary endpoint of overall survival (OS) in the overall study population (intention-to-treat, ITT) were encouraging, but are still immature. Safety for the TECENTRIQ and Avastin combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the Phase II IMmotion150 study. No new safety signals were identified with the combination. The rate of treatment-related Grade 3-4 adverse events was lower with the TECENTRIQ and Avastin combination (40 percent) than with sunitinib alone (54 percent) in all treated patients.

Observations of a pre-specified subgroup analysis of the TECENTRIQ and Avastin combination indicated that, in people whose disease expressed PD-L1, a numerical difference in PFS favoring TECENTRIQ was seen across all patient risk factor groups (favorable, intermediate and poor) compared to sunitinib. In addition, a pre-defined analysis of patient-reported outcomes (PRO) revealed that the combination of TECENTRIQ and Avastin markedly delayed the time to a worsening of disease symptoms that interfere with day-to-day life compared to sunitinib, (median time to deterioration: 11.3 vs. 4.3 months; HR=0.56; 95 percent CI: 0.46, 0.68) in the ITT population. Due to the study design, pre-defined subgroup analyses and pre-defined PRO analyses were not assessed for statistical significance and are descriptive only.

“This is the second positive Phase III study that includes TECENTRIQ and Avastin as part of a treatment regimen, providing further evidence to support the potential of this unique combination,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are encouraged that initial treatment with TECENTRIQ and Avastin significantly reduced the risk of disease worsening or death in people with advanced kidney cancer, while also providing more time before disease symptoms interfered with day-to-day life compared with sunitinib, a current standard of care. We look forward to discussing these results with regulatory authorities worldwide.”

The late-breaking IMmotion151 data will be presented at the 2018 Genitourinary Cancers Symposium on Saturday, Feb. 10 from 1:00-2:00 p.m. Pacific Time (PT) (Abstract #578), and were highlighted as part of the conference’s official press program.

About the IMmotion151 study

IMmotion151 is a Phase III multicenter, randomized, 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 randomized 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 Tumors Version 1.1 (RECIST v1.1) in people whose tumors 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 tumors expressed PD-L1, PFS as determined by an Independent Review Facility (IRF) according to RECIST v1.1, investigator-assessed objective response rate (ORR) and median duration of response (mDOR), 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.

Stratification factors included the Memorial Sloan-Kettering Cancer Center (Motzer) prognostic scoring system, which predicts for OS based upon an individual’s baseline clinical and laboratory characteristics. Depending on the presence of one or several of five variables (risk factors), people are classified in one of the three risk groups: “Favorable” with 0 risk factors, “Intermediate” with 1-2 risk factors and “Poor” with ≥ 3 risk factors.

Phase III IMmotion151 Study Results: Investigator Assessed
Population

PD-L1+ (programmed death-ligand 1: Expression ≥1% on IC)

n = 362

ITT (intent-to-treat)

n = 915

Treatment Arm

Sunitinib

n = 184

TECENTRIQ & Avastin n= 178

Sunitinib

n = 461

TECENTRIQ & Avastin n= 454
PFS Co-Primary Secondary

mPFS

(95% CI)

7.7 months

(6.8, 9.7)

11.2 months

(8.9, 15.0)

8.4 months

(7.5, 9.7)

11.2 months

(9.6, 13.3)

Stratified HR

(95% CI)

0.74

(0.57, 0.96)

P = 0.02

0.83

(0.70, 0.97)

ORR Secondary Secondary

ORR

(95% CI)

35%

(28, 42)

43%

(35, 50)

33%

(29, 38)

37%

(32, 41)

mDOR

(95% CI)

12.9 months

(9.8, NE)

NE

(12.4, NE)

14.2 months

(11.3, NE)

16.6 months

(15.4, NE)

Phase III IMmotion151 Study Results: IRF-Assesseda
Population

PD-L1+ (programmed death-ligand 1: Expression ≥1% on IC)

n = 362

ITT (intent-to-treat)

n = 915

PFS Secondary Secondary

mPFS

(95% CI)

7.2 months

(6.1, 11.1)

8.9 months

(6.9, 12.5)

8.3 months

(7.0, 9.7)

9.6 months

(8.3, 11.5)

Stratified HR

(95% CI)

0.93

(0.72, 1.21)

0.88

(0.74, 1.04)

Initial observations from the co-primary endpoint of overall survival: Descriptive Only
Treatment TECENTRIQ & Avastin Sunitinib TECENTRIQ & Avastin Sunitinib
Population

PD-L1+ (programmed death-ligand 1: Expression ≥1% on IC)

n = 362

ITT (intent-to-treat)

n = 915

Median OS Not reached 23.3 (21.3, NR) Not reached

HR

(95% CI)

0.68

(0.46, 1.00)

0.81

(0.63, 1.03)

Event/patient ratio: PD-L1+, TECENTRIQ and Avastin, 25% and sunitinib, 35%; ITT, TECENTRIQ and Avastin, 27% and sunitinib, 31%. Assessed by investigator; minimum follow-up, 12 mo. Median of follow-up, 15 months.
           

NE, not estimable aData assessed by independent review facility

Difference in IRF-assessed PFS HR driven by IC1/2/3 population (IRF-assessed PFS HR in IC0 was 0.84 compared to 0.93 for Investigator-assessed PFS in IC0) despite study participants being blinded to PD-L1 status. Totality of data support the Investigator assessment of PFS. Preparations for further analyses of IRF-assessed PFS are ongoing.

About renal cell carcinoma

According to the American Cancer Society, more than 63,300 people will be diagnosed with kidney cancer in 2018. Renal cell carcinoma (RCC) accounts for approximately 90 percent of all cases. RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where the blood is filtered. Typically, RCC is a single tumor in one kidney but, in rare cases, there can be multiple tumors, which can occur in one or both kidneys. Despite recent progress in the field of kidney cancer, treatment options for people with the disease remains limited.

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

There is a strong scientific rationale to support further investigation of TECENTRIQ plus Avastin in combination. We are investigating this combination in a broad range of cancers, including advanced RCC. Avastin, in addition to its anti-angiogenic effects, may further enhance TECENTRIQ’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumor infiltration and enabling priming and activation of T-cell responses against tumor antigens.

About TECENTRIQ® (atezolizumab)

TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1. TECENTRIQ is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the re-activation of T cells. TECENTRIQ may also affect normal cells.

About Avastin® (bevacizumab)

Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). Avastin is the only currently available treatment for people with mRCC that directly inhibits VEGF.

TECENTRIQ U.S. Indication (pronounced ‘tē-SEN-trik’)

TECENTRIQ is a prescription medicine used to treat:

a type of bladder and urinary tract cancer called urothelial carcinoma.

  • TECENTRIQ may be used when your bladder cancer:
    • has spread or cannot be removed by surgery (advanced urothelial carcinoma), and
    • you are not able to take chemotherapy that contains a medicine called cisplatin, or
    • you have tried chemotherapy that contains platinum, and it did not work or is no longer working.

The approval of TECENTRIQ in these patients is based on a study that measured response rate and duration of response. There is an ongoing study to confirm clinical benefit.

a type of lung cancer called non-small cell lung cancer (NSCLC)

  • TECENTRIQ may be used when your lung cancer:
    • has spread or grown, and
    • you have tried chemotherapy that contains platinum, and it did not work or is no longer working.

If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

It is not known if TECENTRIQ is safe and effective in children.

For full Prescribing Information on Avastin please visit http://www.avastin.com .

About Genentech in Personalized Cancer Immunotherapy

For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 20 investigational medicines, 10 of which are in clinical trials. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit http://www.gene.com/cancer-immunotherapy .

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

SOURCE: Genentech

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