New Data From the Phase II CITYSCAPE Trial Show Encouraging Results With Genentech’s Novel Anti-TIGIT Tiragolumab Plus Tecentriq

– After 2.5 years median follow-up, pre-planned exploratory analyses in the PD-L1-high population show clinically meaningful results, with overall survival not yet reached and continued progression-free survival improvement for the combination compared with Tecentriq alone –

– CITYSCAPE is the first randomized Phase II trial of an anti-TIGIT therapy and is investigating tiragolumab in PD-L1-positive metastatic non-small cell lung cancer –

– Tiragolumab is the first anti-TIGIT therapy to be granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration –

– CITYSCAPE forms the basis of a broad tiragolumab development program across multiple settings and tumor types –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new follow-up efficacy, safety and patient-reported outcomes (PROs) data from the Phase II CITYSCAPE trial, investigating the novel anti-TIGIT cancer immunotherapy tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone as an initial (first-line) treatment for people with PD-L1-positive metastatic non-small cell lung cancer (NSCLC). The full results are being featured as an oral presentation in the Proffered Paper session 2 (Abstract LBA2) at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2021, taking place December 8-11. ¹

“These encouraging results suggest that combining anti-TIGIT and anti-PD-L1 cancer immunotherapies such as tiragolumab and Tecentriq could potentially represent a novel approach to address unmet needs in cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “With tiragolumab, we have the largest and most advanced anti-TIGIT clinical program, and we look forward to the results of our Phase III trials in lung cancer and other challenging tumor types.”

After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat (ITT) population (n=67), driven by the PD-L1-high population (TPS ≥ 50%) (n=29). In the ITT population, the combination reduced the risk of disease worsening or death (progression-free survival; PFS) by 38% (median PFS=5.6 vs. 3.9 months; hazard ratio [HR]=0.62, 95% CI: 0.42–0.91) and improved overall response rates (ORR) (38.8% vs. 20.6%) compared with Tecentriq alone. A predefined exploratory analysis in the PD-L1-high population showed a 71% reduction in the risk of disease worsening or death (median PFS=16.6 vs. 4.1 months; HR=0.29, 95% CI: 0.15–0.53) and a clinically meaningful improvement in ORR (69% vs. 24.1%) with the combination compared with Tecentriq alone.¹

The analysis also showed that tiragolumab plus Tecentriq improved overall survival (OS), a secondary endpoint of the study, in the ITT population, which was driven by the PD-L1-high population. After 2.5 years median follow-up, median OS was 23.2 vs. 14.5 months (HR=0.69, 95% CI: 0.44–1.07) in the ITT population. The exploratory data in the PD-L1-high population showed a clinically meaningful OS improvement. The median was not reached for the tiragolumab regimen and is projected to be greater than 30.3 months based on the lower confidence interval (NE [30.3-NE] vs. 12.8 months [4.7-24.2]; HR=0.23, 95% CI: 0.10-0.53).¹

Data suggest that the combination was generally well-tolerated, showing similar rates of Grade 3-4 treatment-related adverse events (AEs) when adding tiragolumab to Tecentriq compared with Tecentriq alone (22.4% vs. 25%). The most common all cause AEs (rate greater than 5% difference between study groups) seen with the combination were infusion-related reactions, stiffness, dry skin, fatigue and rash. After longer follow-up, no new safety signals were observed with the combination. Patients generally reported minimal-to-moderate symptoms and generally maintained their quality of life compared with the start of treatment. PRO data from this exploratory analysis showed that lung symptoms, such as dyspnea and pain, did not appear to deteriorate with the addition of tiragolumab to Tecentriq.¹

The CITYSCAPE study forms the basis of an industry-leading development program across multiple settings and tumor types³. The Phase III SKYSCRAPER-01 trial is currently ongoing to confirm these results in the PD-L1-high population, with the goal of bringing this treatment option to patients. Earlier this year, tiragolumab was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration – representing the first anti-TIGIT therapy to be granted this designation and the 37th BTD for Genentech’s portfolio of medicines. Since 2020, Genentech has initiated five Phase III trials evaluating tiragolumab plus Tecentriq in early and metastatic disease in lung (SKYSCRAPER-01, SKYSCRAPER-02, SKYSCRAPER-03) and esophageal cancers (SKYSCRAPER-07, SKYSCRAPER-08). Tiragolumab is also being evaluated in other solid tumors as well as in hematological cancers.

About the CITYSCAPE study¹

CITYSCAPE is a global Phase II, randomized and blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone in 135 patients with first-line PD-L1-positive locally advanced, unresectable or metastatic non-small cell lung cancer. Patients were randomized 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until progressive disease or loss of clinical benefit. Co-primary endpoints are overall response rate (ORR) and progression-free survival (PFS). Secondary endpoints include safety, overall survival (OS) and patient-reported outcomes (PROs). PRO results were assessed with EORTC QLQ-C30, a questionnaire developed to assess the quality of life of people with cancer, administered at baseline and throughout study treatment.

A summary of the results are as follows:

	ITT		PD-L1 TPS >50%		PD-L1 TPS 1-49%
	Placebo plus Tecentriq	Tiragolumab plus Tecentriq	Placebo plus Tecentriq	Tiragolumab plus Tecentriq	Placebo plus Tecentriq	Tiragolumab plus Tecentriq
N	68	67	29	29	39	38
ORR, %	20.6	38.8	24.1	69.0	17.9	15.8
mDOR, mo (95% CI)	10.7 (6.0-18.8)	17.6 (9.1-26.1)	8.2 (5.6-10.4)	15.7 (9.1-NE)	18.8 (15.9-22.8)	17.8 (8.3-24.2)
mPFS, mo (95% CI)	3.9 (2.7-4.5)	5.6 (4.2-10.4)	4.1 (2.1-6.8)	16.6 (5.5-22.3)	3.6 (1.4-5.5)	4 (1.6-5.6)
HR (95% CI)	0.62* (0.42-0.91)		0.29† (0.15-0.53)		1.07 (0.67-1.71)
mOS, mo (95% CI)	14.5 (9.6-20.4)	23.2 (14.1-31.5)	12.8 (4.7-24.2)	NE (30.3-NE)	14.5 (8.3-25.6)	13.3 (8.0-20.7)
HR (95% CI)	0.69* (0.44-1.07)		0.23† (0.10-0.53)		1.16† (0.70-1.94)

*Stratified; †Unstratified; NE = non-evaluable.

Safety overview:

	Placebo plus Tecentriq n=68	Tiragolumab plus Tecentriq n=67
All cause AEs Grade 3-4 Grade 5	66 (97.1%) 27 (39.7%) 7 (10.3%)	66 (98.5%) 35 (52.2%) 3 (4.5%)
Treatment-related AEs Grade 3-4 Grade 5	48 (70.6%) 17 (25%) 0	55 (82.1%) 15 (22.4%) 2 (3%)
Immune mediated AEs Grade 3-4	32 (47.1%) 11 (16.2%)	51 (76.1%) 13 (19.4%)
AEs Leading to withdrawal	9 (13.2%)	10 (14.9%)

About tiragolumab

Tiragolumab is a first-in-class novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer.¹ Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq.² The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway. Dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response.¹

About lung cancer

According to the American Cancer Society, it is estimated that more than 235,000 Americans will be diagnosed with lung cancer in 2021. NSCLC accounts for 80-85% of all lung cancers and approximately 50% of patients diagnosed with NSCLC are diagnosed with early-stage (Stages I and II) or locally advanced (Stage III) disease. Today, about half of all people with early lung cancer still experience a cancer recurrence following surgery. Treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.

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.

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat adults with:

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

• TECENTRIQ may be used alone as a treatment for their lung cancer:
  • to help prevent their lung cancer from coming back after their tumor(s) has been removed by surgery and they have received platinum-based chemotherapy, and
  • they have stage 2 to 3A NSCLC (patients should talk to their healthcare provider about what these stages mean), and
  • their cancer tests positive for “PD-L1”.

• Tecentriq may be used alone as their first treatment when their lung cancer:
  • has spread or grown, and
  • their cancer tests positive for “high PD-L1”, and
  • their tumor does not have an abnormal “EGFR” or “ALK” gene

• Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as their first treatment when their lung cancer:
  • has spread or grown, and
  • is a type called “non-squamous NSCLC,” and
  • their tumor does not have an abnormal “EGFR” or “ALK” gene

• Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as their first treatment when their lung cancer:
  • has spread or grown, and
  • is a type called “non-squamous NSCLC,” and
  • their tumor does not have an abnormal “EGFR” or “ALK” gene

• Tecentriq may also be used when their lung cancer:
  • has spread or grown, and
  • they have tried chemotherapy that contains platinum, and it did not work or is no longer working
    • if their tumor has an abnormal “EGFR” or “ALK” gene, they 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 the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended.

Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including:

Lung problems

• cough
• shortness of breath
• chest pain

Intestinal problems

• diarrhea (loose stools) or more frequent bowel movements than usual
• stools that are black, tarry, sticky, or have blood or mucus
• severe stomach-area (abdomen) pain or tenderness

Liver problems

• yellowing of the skin or the whites of the eyes
• severe nausea or vomiting
• pain on the right side of their stomach area (abdomen)
• dark urine (tea colored)
• bleeding or bruising more easily than normal

Hormone gland problems

• headaches that will not go away or unusual headaches
• eye sensitivity to light
• eye problems
• rapid heartbeat
• increased sweating
• extreme tiredness
• weight gain or weight loss
• feeling more hungry or thirsty than usual
• urinating more often than usual
• hair loss
• feeling cold
• constipation
• their voice gets deeper
• dizziness or fainting
• changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems

• decrease in their amount of urine
• blood in their urine
• swelling of their ankles
• loss of appetite

Skin problems

• rash
• itching
• skin blistering or peeling
• painful sores or ulcers in mouth or nose, throat, or genital area
• fever or flu-like symptoms
• swollen lymph nodes

Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including:

• Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
• Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
• Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
• Persistent or severe muscle pain or weakness, muscle cramps
• Low red blood cells, bruising

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

• chills or shaking
• itching or rash
• flushing
• shortness of breath or wheezing
• dizziness
• feeling like passing out
• fever
• back or neck pain

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq. A healthcare provider will monitor for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to delay or completely stop treatment with Tecentriq if patients have severe side effects.

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 received an organ transplant
• have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
• have received radiation treatment to their chest area
• have a condition that affects their nervous system, such as myasthenia gravis or Guillain-Barré syndrome
• are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
  • A healthcare provider should do a pregnancy test before they start treatment with Tecentriq
  • They should use an effective method of birth control during their 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. Patients should 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 when used alone include:

• feeling tired or weak
• decreased appetite
• nausea
• cough
• shortness of breath

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

• feeling tired or weak
• nausea
• hair loss
• constipation
• diarrhea
• decreased appetite

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 about the benefits and side effects of Tecentriq.

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 see http://www.Tecentriq.com for full Prescribing Information and additional Important Safety Information.

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentech’s approved PD-L1 checkpoint inhibitor, the company’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. 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 five 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 and 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.

References

¹ Cho BC, Rodriguez-Abreu D, et al. Updated analysis and patient-reported outcomes from CITYSCAPE: a randomized, double-blind, Phase II study of the anti-TIGIT antibody tiragolumab + atezolizumab vs placebo + atezolizumab as first-line treatment for PD-L1+ NSCLC. Presented at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2021; 2021 December 8-11. Abstract #LBA2.
² Johnston RJ, Comps-Agrar L, et al. Cancer Cell. 2014;26(6):923-937.
³ National Institutes of Health. U.S. National Library of Medicine. Clinicaltrials.gov (NCT02794571; NCT03563716; NCT04294810; NCT04256421; NCT04513925; NCT04300647; NCT04832854; NCT04619797; NCT04543617; NCT04540211; NCT04665843; NCT03193190; NCT03281369; NCT03869190; NCT04524871; NCT04584112; NCT04045028; NCT02794571). [Last accessed 08 Dec 2021]. Available from: https://clinicaltrials.gov/.