Saturday, Sep 26, 2015

Two Positive Studies of Genentech’s Investigational Cancer Immunotherapy Atezolizumab in Specific Type of Lung Cancer Presented at 2015 European Cancer Congress

Phase II POPLAR study demonstrated statistically significant survival benefit compared to chemotherapy

PD-L1 expression correlated with how well people did on atezolizumab

Data will be submitted to global health authorities, including the U.S. Food and Drug Administration (FDA)

South San Francisco, CA -- September 26, 2015 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive results from two Phase II studies that evaluated the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in people with advanced non-small cell lung cancer (NSCLC). In the randomized Phase II study, POPLAR, atezolizumab met its primary endpoint and showed a statistically significant survival benefit compared to chemotherapy (HR=0.54; p=0.014) in people with recurrent NSCLC whose tumors expressed medium and high levels of PD-L1, which corresponded with people living 7.7 months longer than people who received docetaxel chemotherapy. A separate, single-arm 

Phase II study, BIRCH, met its primary endpoint and showed that atezolizumab shrank tumors (objective response rate, ORR) in up to 27 percent (p=0.0001) of people whose disease had progressed on prior medicines and also expressed the highest levels of PD-L1. Median survival had not yet been reached. In both studies of atezolizumab, adverse events were consistent with those observed in previous studies.

“Results from both of our studies in non-small cell lung cancer showed that measuring PD-L1 may help identify people most likely to respond to atezolizumab, and the majority of responses continued when these data were assessed,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Durable responses are meaningful for people whose cancer has progressed on other medicines, and we plan to submit these results to global health authorities to bring this potential new option to people as soon as possible.”

In February 2015, atezolizumab received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of people whose NSCLC expresses PD-L1 and whose disease worsened during or after standard treatments (e.g., platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). Genentech is discussing these data in NSCLC from POPLAR and BIRCH with the FDA as part of its Breakthrough Therapy Designation, and with other health authorities around the world. Genentech currently has seven ongoing Phase III studies of atezolizumab alone or in combination with other medicines for various types of lung cancer.

About the POPLAR Study

Full results of the POPLAR study will be presented by Johan Vansteenkiste, University Hospital Leuven, Leuven, Belgium (Abstract #14LBA) on Sunday, Sept. 27, 9:15 a.m. Central European Time (CET).

Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung cancer: Primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II study (POPLAR)

POPLAR is a multicenter, open-label, randomized Phase II study evaluating the efficacy and safety of atezolizumab compared with docetaxel in people with recurrent locally advanced or metastatic NSCLC. People were randomized to receive either atezolizumab 1200 mg intravenously every three weeks or docetaxel 75 mg/m2 intravenously every three weeks. Treatment with atezolizumab may have been continued as long as people were experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression. The study enrolled 287 people with previously treated, advanced NSCLC. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), ORR and safety. People were stratified by PD-L1 expression on tumor-infiltrating immune cells (ICs), histology and prior lines of therapy. PD-L1 expression was assessed for both tumor cells (TCs) and ICs; people were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3 with an investigational immunohistochemistry (IHC) test being developed by Roche Diagnostics.

 

POPLAR Efficacy Data

Study Group

ITT

(All Patients)

TC3 or IC3

(High)

TC2/3 or IC2/3

(Medium and High)

TC1/2/3 or

IC1/2/3

(Any Expression)

TC0 and IC0

 

n=

A
144

D
143

A
24

D
23

A
50

D
55

A
93

D
102

A
51

D
41

                     

 

          OS

Median, mo

12.6

9.7

15.5

11.1

15.1

7.4

15.5

9.2

9.7

9.7

HR*

(95% CI)

P value

0.73

(0.53-0.99)

0.040

0.49

(0.22-1.07)

0.068

0.54

(0.33-0.89)

0.014

0.59

(0.4-0.85)

0.005

1.04

(0.62-1.75)

0.871

         PFS

Median, mo

2.7

3.0

7.8

3.9

3.4

2.8

2.8

3.0

1.7

4.1

HR

(95% CI)

0.94
(0.72
-1.23)

0.60
(0.31
-1.16)

0.72
(0.47
-1.10)

0.85
(0.63
-1.16)

1.12
(0.72
-1.77)

ORR, % (confirmed)

15

15

38

13

22

15

18

17

8

10

Of the ITT population who responded, 57 percent in atezolizumab and 24 percent in docetaxel continued to respond at the time when the data was assessed.

A: atezolizumab; D: docetaxel; HR: hazard ratio; CI: confidence interval; TC: tumor cell; IC: tumor-infiltrating immune cell; OS: overall survival; PFS: progression-free survival; ORR: objective response rate; ITT: intention to treat; *Stratified HR for ITT and unstratified HR for subgroups.

Safety was assessed in 142 people and adverse events were consistent with those observed in previous studies of atezolizumab. People receiving atezolizumab experienced fewer treatment-related Grade 3-4 adverse events compared to docetaxel (11 percent vs. 39 percent), and fewer treatment-related Grade 5 adverse events (1 percent vs. 2 percent). Adverse events occurring more frequently (5 percent or more) for atezolizumab included decreased appetite, shortness of breath (dyspnea), fever (pyrexia), joint or joint and muscle pain (arthralgia and musculoskeletal pain), insomnia, pneumonia and hypothyroidism.

About the BIRCH Study

Interim results of the BIRCH study will be presented by Benjamin Besse, Institut Gustave Roussy, Villejuif France and Paris Sud University, France (Abstract #16LBA) on Sunday, Sept. 27, 9:35 a.m. CET.

Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic, PD-L1-selected NSCLC

BIRCH is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of atezolizumab in 667 people with locally advanced or metastatic NSCLC whose disease expressed PD-L1. PD-L1 expression was assessed for both TCs and ICs with an investigational IHC test being developed by Roche Diagnostics. Eligibility criteria included people whose tumors were determined to express PD-L1 with an IHC score of TC2/3 or IC2/3. People in the study received a 1200-mg intravenous dose of atezolizumab every three weeks. The primary endpoint of the study was the ORR assessed by independent review facility per RECIST v1.1. Secondary endpoints included duration of response, OS, PFS and safety.

BIRCH Efficacy Data

 

First-line

Second-line

Third-line or More

Study Group

TC3 or IC3

(High)

TC2/3 or IC2/3

(Medium and High)

TC3 or IC3

(High)

TC2/3 or IC2/3

(Medium and High)

TC3 or IC3

(High)

TC2/3 or IC2/3

(Medium and High)

n=

65

139

122

267

115

253

ORR, %a,b

(95% CI)

26

(16, 39)

19

(13, 27)

24

(17, 32)

17

(13, 22)

27

(19, 36)

17

(13, 23)

More than 61 percent of people whose tumors expressed the highest level of PD-L1 continued to respond at time data was assessed.

6-mo PFS, %b

(95% CI)

48

(35, 61)

46

(37, 55)

34

(26, 43)

29

(23, 34)

39

(30, 48)

31

(25, 37)

6-mo OS, %

(95% CI)

79

(69, 89)

82

(75, 88)

80

(72, 87)

76

(71, 81)

75

(67, 83)

71

(65, 76)

aConfirmed; bIRF. CI: confidence interval; TC: tumor cell; IC: tumor-infiltrating immune cell; ORR: objective response rate; PFS: progression-free survival; OS: overall survival; IRF: independent review facility.

 

Safety was assessed in 659 people and adverse events were consistent with those observed in previous studies of atezolizumab. Eleven percent of people experienced Grade 3-4 treatment related adverse events. The most common treatment-related adverse events were fatigue, diarrhea, nausea, itching (pruritus), fever (pyrexia), decreased appetite, weakness (asthenia), rash and joint pain (arthralgia).

About Lung Cancer

According to the American Cancer Society, it is estimated that more than 221,000 Americans will be diagnosed with lung cancer in 2015, and NSCLC accounts for 85 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

About Atezolizumab

Atezolizumab (also known as MPDL3280A; anti-PDL1) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.

All studies of atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both tumor cells and infiltrating immune cells. The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with atezolizumab alone, and to determine which people may benefit most from a combination of atezolizumab and another medicine. There are 11 ongoing or planned Phase III studies of atezolizumab across certain kinds of lung, kidney, breast and bladder cancer.

About Genentech in 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, seven 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/immunotherapy.

About Genentech

Founded more than 35 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.

 

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