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

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) –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (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 percent 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 tumor 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 randomized 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,” said Sandra Horning, M.D., 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 for Medical Oncology (ESMO) Immuno Oncology Congress (Abstract #LBA1_PR) on Thursday, December 7, 6:15 p.m. Central European Time (CET) and are also part of the official press program. 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 multicenter, open-label, randomized, 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 randomized (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) vs. 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 Tumors 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.

Primary PFS Analysis (ITT-WT Population; Co-Primary Endpoint)
   

Arm C

Avastin + carboplatin
+ paclitaxel

 

Arm B

TECENTRIQ & Avastin +
carboplatin + paclitaxel

ITT-WT populationa   n = 336   n = 356
Median PFS

(95% CI), months

  6.8 (6.0, 7.1)   8.3 (7.7, 9.8)
HR

(95% CI)

p-value

  0.62

(0.52 - 0.74)

p < 0.0001

ITT-WT Landmark PFS
6-month (95% CI)   56% (51, 62)   67% (62, 72)
12-month (95% CI)   18% (13, 23)   37% (31, 42)
Primary ORR Analysis (Secondary Endpoint)
ITT-WT ORR

(95% CI)

  48% (43, 54)   64% (58, 68)

Independent review facility (IRF)-assessed PFS demonstrated a similar benefit with Arm B vs Arm C as INV-assessed PFS in the ITT-WT population

Primary PFS Analysis (Teff-WT Population; Co-Primary Endpoint)
   

Arm C

Avastin + carboplatin
+ paclitaxel

 

Arm B

TECENTRIQ & Avastin +
carboplatin + paclitaxel

Teff-WT populationa   n = 129   n = 155
Median PFS

(95% CI), months

  6.8 (5.9, 7.4)   11.3 (9.1, 13.0)
HR

(95% CI)

p-value

  0.51

(0.38 - 0.68)

p < 0.0001

Teff-WT Landmark PFS
6-month (95% CI)   57% (48, 66)   72% (65, 79)
12-month (95% CI)   18% (10, 25)   46% (38, 54)
Teff Primary ORR Analysis (Secondary Endpoint)
Teff ITT-WT ORR

(95% CI)

  54% (44, 62)   69% (61, 76)

IRF-assessed PFS showed a similar benefit for Arm B vs. Arm C as INV-assessed PFS in the Teff-WT population

PFS Subgroup Analysis (HR; 95% CI) (Arm B vs. C)
ITT (Includes EGFR mutant & ALK+)*   0.61 (0.52, 0.72)
EGFR mutant & ALK+*   0.59 (0.37, 0.94)
Teff negative-WT   0.76 (0.60, 0.96)
PDL1 by IHC

TC1/2/3 - IC 1/2/3-WT

  0.50 (0.39, 0.64)
PDL1 by IHC

TC2/3 - IC2/3-WT

  0.48 (0.35, 0.65)
PDL1 by IHC

TC0 and IC0–WT

  0.77 (0.61, 0.99)

HR, hazard ratio; ORR, overall response rate; PFS, progression-free survival; WT, wild-type; Teff, T-effector; IC, tumor-infiltrating immune cells; TC, tumor cells

a

 

WT populations exclude patients with EGFR or ALK driver mutations.

*

Inclusion criteria included people with an EGFR mutation who had experienced disease progression (during or after treatment) or intolerance to treatment with one or more EGFR TKIs or people with an ALK mutation who experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors

.

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 lung cancer

According to the American Cancer Society, it is estimated that more than 222,000 Americans will be diagnosed with lung cancer in 2017, 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 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 first-line advanced NSCLC. 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).

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.

Important Safety Information

Important Information About TECENTRIQ

TECENTRIQ can cause the immune system to attack normal organs and tissues in many areas of the body and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat a patient with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with TECENTRIQ if a patient has severe side effects.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

TECENTRIQ can cause serious side effects, including:

  • Lung Problems (pneumonitis) – Signs and symptoms of pneumonitis may include: new or worsening cough, shortness of breath, or chest pain
  • Liver Problems (hepatitis) – Signs and symptoms of hepatitis may include: yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, feeling less hungry than usual
  • Intestinal Problems (colitis) – Signs and symptoms of colitis may include: diarrhea (loose stools) or more bowel movements than usual, blood in the stools or dark, tarry, sticky stools, severe stomach area (abdomen) pain or tenderness
  • Hormone Gland Problems (especially the pituitary, thyroid, adrenal glands and pancreas) – Signs and symptoms that the hormone glands are not working properly may include: headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, voice gets deeper, urinating more often than usual, nausea or vomiting, stomach area (abdomen) pain
  • Nervous System Problems (neuropathy, meningitis, encephalitis) – Signs and symptoms of nervous system problems may include: severe muscle weakness, numbness or tingling in hands and feet, fever, confusion, changes in mood or behavior, extreme sensitivity to light, neck stiffness
  • Inflammation of the Eyes – Signs and symptoms may include blurry vision, double vision, other vision problems, eye pain or redness
  • Severe Infections – Signs and symptoms of infection may include: fever, cough, frequent urination, flu-like symptoms, pain when urinating
  • Severe Infusion Reactions – Signs and symptoms of infusion reactions may include: chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling like passing out, back or neck pain, and swelling of the face or lips

Before receiving TECENTRIQ, patients should tell their healthcare provider about all of their medical conditions, including if they:

  • Have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects their nervous system (such as myasthenia gravis, or Guillain-Barre syndrome); or are being treated for an infection
  • Are pregnant or plan to become pregnant TECENTRIQ can harm an unborn baby If patients are able to become pregnant, they should use an effective method of birth control during treatment and for at least 5 months after the last dose of TECENTRIQ
  • Are breastfeeding or plan to breastfeed It is not known if TECENTRIQ passes into the breast milk Do not breastfeed during treatment and for at least 5 months after the last dose of TECENTRIQ

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of TECENTRIQ in people with urothelial carcinoma include:

  • feeling tired
  • decreased appetite
  • nausea
  • constipation
  • urinary tract infection
  • diarrhea
  • fever

The most common side effects of TECENTRIQ in people with non-small cell lung cancer include:

  • feeling tired
  • decreased appetite
  • shortness of breath
  • cough
  • nausea
  • muscle or bone pain
  • constipation

TECENTRIQ may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of TECENTRIQ. Patients should ask their healthcare provider or pharmacist for more information.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Tecentriq.com for the TECENTRIQ full Prescribing Information for additional Important Safety Information.

Avastin Indications:

  • Metastatic colorectal cancer (mCRC) for first- or second-line treatment in combination with intravenous 5-fluorouracil–based chemotherapy. It is also approved to treat mCRC for second-line treatment when used with fluoropyrimidine-based (combined with irinotecan or oxaliplatin) chemotherapy after cancer progresses following a first-line treatment that includes Avastin. Avastin is not approved for use after the primary treatment of colon cancer that has not spread to other parts of the body.
  • Advanced nonsquamous non–small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel in people who have not received chemotherapy for their advanced disease.
  • Metastatic kidney cancer (mRCC) when used with interferon alfa.
  • Glioblastoma (GBM) in adult patients whose cancer has progressed after prior treatment (recurrent or rGBM).
  • Advanced cervical cancer (CC) in combination with paclitaxel and cisplatin or paclitaxel and topotecan is approved to treat persistent, recurrent, or metastatic cancer of the cervix.
  • Recurrent ovarian cancer (rOC). Avastin in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan, is approved to treat platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (prOC) in women who received no more than two prior chemotherapy treatments. Avastin, either in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by Avastin alone, is approved for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (psOC).

Possible serious side effects

Everyone reacts differently to Avastin therapy. So it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not. Their doctor will stop treatment if any serious side effects occur. Patients should talk to their doctor if there are any signs of these side effects.

Most serious side effects (not common, but sometimes fatal):

  • GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
  • Wounds that don’t heal. A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgical wounds are fully healed
  • Serious bleeding. This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If a patient has recently coughed up blood or had serious bleeding, they should be sure to tell their doctor

Other possible serious side effects

  • Abnormal passage in the body. This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
  • Severe high blood pressure. Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
  • Kidney problems. These may be caused by too much protein in the urine and can sometimes be fatal
  • Infusion reactions. These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. The patient’s doctor or nurse will monitor for signs of infusion reactions
  • Severe stroke or heart problems. These may include blood clots, mini-stroke, heart attack, chest pain, and the heart may become too weak to pump blood to other parts of the body (congestive heart failure). These can sometimes be fatal
  • Nervous system and vision problems. Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness

Side effects seen most often

In clinical studies across different types of cancer, some patients experienced the following side effects:

  • High blood pressure
  • Too much protein in the urine
  • Nosebleeds
  • Rectal bleeding
  • Back pain
  • Headache
  • Taste change
  • Dry skin
  • Inflammation of the skin
  • Inflammation of the nose
  • Watery eyes

Avastin is not for everyone

Patients should talk to their doctor if they are:

  • Undergoing surgery. Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
  • Pregnant or think they are pregnant. Data have shown that Avastin may harm a woman’s unborn baby. Birth control should be used while patients are on Avastin. If Avastin is stopped, patients should keep using birth control for 6 months before trying to become pregnant
  • Planning to become pregnant. Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children.
  • Breastfeeding. Breastfeeding while on Avastin may harm the baby and is therefore not recommended

Patients should talk with their doctor if they have any questions about their condition or treatment.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

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 in Lung Cancer

Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have four approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

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.

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