A Door Opens

“Heads up, we got incoming!!!”

For Drs. Ira Mellman and Dan Chen, May 18, 2016 started out like any other day—the usual bustle and rush of the morning routine, the commute to the Genentech campus in South San Francisco and, in Chen’s case, a 7 a.m. meeting. Then, at 9:38 a.m., his cell phone started buzzing.

The “Heads up” text was from Dr. O. Daejin Abidoye. Abidoye is a member of the atezolizumab team, serving as the clinical filing lead for the multi-year effort toward the U.S. Food and Drug Administration (FDA) approval of Genentech’s first cancer immunotherapy. Normally, Chen wouldn’t keep checking his phone during a meeting, but these weren’t normal circumstances. The team had been told to expect news on the FDA’s decision any day now. That was last week. After anxious days of silence, Chen knew this might be history in the making.

Until recently, the notion that the immune system could be effectively enlisted to fight cancer may have been considered, at best, wishful thinking. Now it represented a scientific cutting edge in cancer treatment—the breakthrough that Chen, an oncologist, immunologist and vice president in charge of Genentech’s late stage global cancer immunotherapy development program, and Mellman, a well-respected cell biologist, immunologist and Genentech’s vice president of research cancer immunology, had been searching for their entire professional lives.

Their cancer medicine, atezolizumab (now known as TECENTRIQ®) Indication and Important Safety Information, was poised to be Genentech’s first cancer immunotherapy. The clinical trials also indicated it had potential to be the first significant drug development for people with previously treated advanced bladder cancer in more than 30 years. Now, all they needed was FDA approval.

Even after years of work, time was of the essence.

At 9:41 a.m., Chen’s pocket was still buzzing. Abidoye was texting emoticons now—smiley faces with gritted teeth. Did that mean nervous? The data were impressive, they’d worked tirelessly, but as Chen had cautioned his team, no outcome was ever certain. And so despite his confidence, he wondered—was there something to be nervous about?

“Stay tuned …” Abidoye had written. But by 9:45 a.m., Chen had already excused himself from the room and was jogging toward the stairs.

For the previous six months, the 4th floor of a building on the Genentech campus had been cordoned off for the team working to prepare the FDA submission for the investigational molecule. Now Chen emerged from the stairwell to find the filing team’s office already crowded with members of the atezolizumab team, including Dr. Gregg Fine, genitourinary global development lead, Kathleen Winson, global regulatory leader and Cathi Ahearn, life cycle team leader. Like many on the team, they had worked hard—years of days and nights and weekends—and now they were electric with anticipation and staring at Abidoye and his colleague, Jerald Grace, Pharm.D., the U.S. regulatory filing lead.

Grace stared at his email inbox, hitting the refresh button and waiting.

“Even after years of work, time was of the essence,” Chen explains. “Every day, we’d been racing against the clock. It was intense, because every day patients are struggling with this disease.”

The estimated 8,000 people diagnosed with advanced bladder cancer in the U.S. in 2016 had few options besides radical surgery and chemotherapy.1,2

“We intend to change this,” Chen had said to his team.

“There was an urgent need for new treatment options for advanced bladder cancer,” Chen explains. “We based our research decisions on scientific observation and had a strong hypothesis—but really, nobody knew what would happen. In my opinion, advanced bladder cancer was considered to be a minefield.”

Chen and Mellman had worked together at Genentech since 2007 when Mellman relocated from a professorship at Yale Medical School. Together, they helped guide Genentech’s research and drug development in immunotherapy and provided the foundational framework for cancer immunotherapy research, known as The Cancer-Immunity Cycle.

Starting from scratch, they’d quickly ramped up Genentech’s focus on a promising and unique target for drug development, which could impact many cancer types, including advanced bladder cancer, an underserved form of bladder cancer.

“In only a few years, cancer immunotherapy has evolved to become a key area of the oncology landscape,” Mellman explains. “The whole process has been so exciting—it’s not just one moment or development, it’s the progress made across the whole field of immunotherapy. How often do you get to experience a paradigm shift of this magnitude?”

In the spring of 2013, the atezolizumab team received the first indication that perhaps they had changed things.

Less than two weeks after some advanced bladder cancer patients received an initial dose of atezolizumab in the first Phase I clinical trial, investigators saw early evidence that the medicine appeared to be working. The team knew they had to get atezolizumab through clinical trials and to patients quickly.

While some advanced bladder cancer patients may have been involved in the Phase I and II studies of the medicine at major health centers, “those studies touch just a tiny fraction of advanced bladder cancer patients,” Fine explains. Most advanced bladder cancer patients are treated by local oncologists, often far from clinical trial sites where they might receive investigational medicines; in fact, Ahearn says, the cancer immunotherapy field was moving so fast, many had no idea atezolizumab was even being studied.

It was excitement and relief, reflection and forward-looking, all at once!

The promising early results prompted the FDA to grant atezolizumab Breakthrough Therapy Designation in May of 2014, expediting the development and review of the medicine. But only FDA approval would allow atezolizumab to be made available to the many patients in need Indication and Important Safety Information. Within 24 hours of approval, the medicine would be loaded onto planes en route to hospitals and clinics across the country; within 48 hours, the first patients would begin infusion. For the teams huddled anxiously at Genentech, and for patients in the U.S., there was no time to lose.

“DING.”

At 10:06 a.m., Grace blinked at the familiar sound of mail hitting his inbox. It was from the FDA. He leaned forward.

“In reference to your Biologics License Application …”

TECENTRIQ® (atezolizumab) Indication and Important Safety Information received accelerated approval for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). TECENTRIQ is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.3



Possible serious side effects with TECENTRIQ include, but are not limited to, lung problems (pneumonitis), liver problems (hepatitis), intestinal problems (colitis), hormone gland problems (especially the pituitary, thyroid, adrenal glands and pancreas), nervous system problems (neuropathy, meningitis and encephalitis), eye problems (inflammation of the eyes), severe infections and severe infusion reactions. Additional information on these and other side effects can be found below.




There in the images, caught in camera flashes and phone video: the hoots and cheers and high fives and hugs. For Chen, news of the accelerated approval4 brought a “powerful release of emotion.” The steps that built up to the ultimate moment of approval—the research, the very first cancer patient to respond, finishing the pivotal trials—they all flashed rapid-fire before his eyes, like a slideshow.

“It was excitement and relief, reflection and forward-looking, all at once!” Chen remembers. “It was a very powerful moment—and a mark in Genentech’s history.”

But amazingly, looking back, Mellman doesn’t really remember that moment at all—he was already thinking ahead.

“I’m one of the most impatient people I know—that’s my personal affliction,” he laughs. “Usually, in drug development, you work on a drug, and if you’re successful, that’s the end of the story,” he explains. “But with cancer immunotherapy, it’s the opposite. We knew this would be just the beginning. With every breakthrough, right away, the question becomes ‘OK, that’s good—so what can we do next?’”

The coming days would be full of whoops and claps, speeches and balloons, and grown men and women, including Chen and Abidoye, leaping with raw joy. Even Mellman would allow himself a moment, joyfully ringing a little celebratory bell.

It was a remarkable moment. But, everyone knew, it was only a moment. A door had opened, for researchers and patients alike.

Read the companion piece: The Simplicity of It.


What it Treats

What is TECENTRIQ?

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

What is the most important information about TECENTRIQ?

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

Call or see your healthcare provider right away if you 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 may include new or worsening cough, shortness of breath, and chest pain
  • Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and 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 your stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
  • Hormone gland problems (especially the pituitary, thyroid, adrenal glands, and pancreas)–signs and symptoms that your 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, your voice gets deeper, urinating more often than usual, nausea or vomiting, and 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, and neck stiffness
  • Inflammation of the eyes–signs and symptoms may include blurry vision, double vision, or other vision problems, eye pain or redness
  • Severe infections–signs and symptoms of infection may include fever, cough, frequent urination, flu-like symptoms, and 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 your face or lips

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

Before you receive TECENTRIQ, tell your healthcare provider about all your medical conditions, including if you:

  • 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 your 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 your unborn baby. If you are able to become pregnant, you should use an effective method of birth control during your 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 your breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of TECENTRIQ

Tell your healthcare provider about all the medicines you 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. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of TECENTRIQ. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information.

1. National Cancer Institute. SEER Stat Fact Sheets: Bladder Cancer. http://seer.cancer.gov/statfacts/html/urinb.html. Accessed September 9, 2016.
2. American Society of Clinical Oncology. Bladder Cancer: Treatment Options. http://www.cancer.net/cancer-types/bladder-cancer/treatment-options. Last updated 5/2016. Accessed October 3, 2016.
3. TECENTRIQ Prescribing Information. South San Francisco, Calif.: Genentech, Inc. 2016.
4. Genentech. FDA Grants Genentech’s Cancer Immunotherapy TECENTRIQ™ (atezolizumab) Accelerated Approval for People with a Specific Type of Advanced Bladder Cancer. May 18, 2016. Retrieved October 11, 2016 from: https://www.gene.com/media/press-releases/14626/2016-05-18/fda-grants-genentechs-cancer-immunothera