What is TECENTRIQ®?

TECENTRIQ is an Fc-engineered, humanised immunoglobulin G1 (IgG1) monoclonal antibody that directly binds to PD-L1 and provides a dual blockade of the PD-1 and B7.1 receptors, releasing PD-L1/PD-1 mediated inhibition of the immune response, including reactivating the antitumour immune response without inducing antibody-dependent cellular cytotoxicity.

Programmed death-ligand 1 (PD-L1) may be expressed on tumour cells and/or tumour-infiltrating immune cells, and can contribute to the inhibition of the antitumour immune response in the tumour microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T-cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production.

TECENTRIQ spares the PD-L2/PD-1 interaction allowing PD-L2/PD-1 mediated inhibitory signals to persist.1

Indications

 


TECENTRIQ (atezolizumab) in combination with nab-paclitaxel is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumours have PD-L1 expression ≥ 1% and who have not received prior chemotherapy for metastatic disease.

TECENTRIQ, in combination with Avastin (bevacizumab), paclitaxel and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous non-small cell lung cancer (mNSCLC). In patients with EGFR mutant or ALK-positive mNSCLC, TECENTRIQ, in combination with bevacizumab, paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies.

TECENTRIQ as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. Patients with EGFR activating mutations or ALK-positive tumour mutations should also have received targeted therapy before receiving TECENTRIQ.

TECENTRIQ as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC):

  • after prior platinum‑containing chemotherapy, or

  • who are considered cisplatin ineligible, and whose tumours have a PD-L1 expression ≥5%

Breast Cancer

1L TNBC / IMpassion130

The first cancer immunotherapy combination to extend survival in PD-L1+ advanced TNBC for 1L treatment*

Phase III, double-blind, two-arm, multi-center, international, randomised, placebo-controlled study in patients with unresectable locally advanced or metastatic TNBC who had not received prior chemotherapy for metastatic disease.

Co-primary endpoints: overall survival (OS) & progression-free survival (PFS) in the intention-to-treat (ITT) population and in patients with PD-L1 expression ≥ 1%.

Key secondary endpoints: overall response rate (ORR), duration of response (DoR).

A total of 902 patients were enrolled and were randomised (1:1) to receive TECENTRIQ in combination with nab-paclitaxel, or nab-paclitaxel only. Patients were stratified by presence of liver metastases, prior taxane treatment, and by PD-L1 expression status in tumour-infiltrating immune cells (IC) (PD-L1 stained tumour-infiltrating immune cells [IC] <1% of tumour area vs ≥ 1% of the tumour area) assessed by the VENTANA PD-L1 (SP142) Assay.

TECENTRIQ in combination with nab-paclitaxel showed survival benefit against nab-paclitaxel in mTNBC patients with PD-L1 expression ≥ 1%.1,10*

There was a statistically significant and meaningful benefit in median PFS in the population with PD-L1+ tumours treated with TECENTRIQ in combination with nab-paclitaxel vs nab-paclitaxel alone (7.5 months vs 5.0 months; HR=0.62; 95% CI,0.49,0.78; P<0.001)​

 

chart1_breast_cancer

nab-pac= nab-paclitaxel

There was a clinically meaningful improvement in median OS in the population with PD-L1+ tumours treated with TECENTRIQ in combination with nab-paclitaxel vs nab-paclitaxel alone (25 months vs 18 months; HR=0.71; 95% CI, 0.54,0.93)*

nab-pac= nab-paclitaxel
*As per the prespecified analysis hierarchy, OS comparisons between treatment arms in the PD-L1+ population were not formally tested in this interim analysis, and the result is provided for descriptive purposes only.

Expression of PD-L1≥1% in IC was predictive of benefit in patients undergoing treatment with TECENTRIQ in combination with nab-paclitaxel.1*

HR= hazard ratio
nab-pac= nab-paclitaxel
*As per the prespecified analysis hierarchy, OS comparisons between treatment arms in the PD-L1+ population were not formally tested in this interim analysis, and the result is provided for descriptive purposes only.


Testing TNBC patients for PD-L1 status at metastatic diagnosis will help you select patients for TECENTRIQ in combination with nab-paclitaxel and improve 1L outcomes

 

Learn more about the safety profile of TECENTRIQ in combination with nab-paclitaxel.

Lung Cancer

1L mNSCLC / IMpower150

Phase III multicentre, international, randomised, open-label, 3-arm trial evaluating TECENTRIQ in combination with carboplatin/paclitaxel with or without Avastin (bevacizumab) in chemotherapy-naïve patients with metastatic non-squamous mNSCLC.

During ESMO 2018, Prof. Martin Reck, MD, PhD (Principal investigator of the IMpower150 trial) from Grosshansdorf Lung Clinic, Grosshansdorf, Germany provided a summary of the trial design and its key results.

This video has been produced and funded by VJ Oncology. F. Hoffmann-La Roche Ltd did not participate in the filming or editing of this video. The video reflects independent opinions of the speaker. F. Hoffmann-La Roche Ltd has been given permission to publish this video here. Prof. Martin Reck has also provided explicit permission for this video to be presented here.

Co-primary endpoints: overall survival (OS) & progression-free survival (PFS). Key secondary endpoints: overall response rate (ORR), duration of response (DoR).

A total of 1,202 patients were enrolled and were randomised (1:1:1) to receive TECENTRIQ in combination with carbo/pac with or without Avastin. Data only from the TECENTRIQ+Avastin+carbo/pac versus Avastin & carbo/pac arm are shown in the results

TECENTRIQ* combination: demonstrated survival benefit against a proven regimen in mNSCLC.1

  • Median OS was higher in TECENTRIQ* combination vs Avastin+carbo/pac arm (19.8 months vs 14.9 months; HR=0.76 (95% CI, 0.63, 0.93; P<0.006).

  • Median 12-month PFS was greater in TECENTRIQ* combination vs Avastin+carbo/pac (38% vs 20%; HR=0.59; 95% CI,0.50,0.69; P<0.0001)​

​​TECENTRIQ* is the first cancer immunotherapy combination to demonstrate clinically meaningful survival in EGFR/ALK+ and liver metastases mNSCLC patients.1,2

HR= Hazard ratio
ITT= Intention-to-treat

  • First cancer immunotherapy to show meaningful OS advantage in EGFR/ALK+ patients treated with TECENTRIQ* combination who have progressed on TKIs (not reached vs 17.5 months; HR= 0.54; 95% CI, 0.29, 1.03) and liver metastases patients (13.3 months vs 9.4 months; HR 0.52 (95% CI, 0.33, 0.82).

DURABLE RESPONSES WITH TECENTRIQ* COMBINATION THERAPY1,2

  • ORR was 56.4% (95% CI, 51.4, 61.4) with TECENTRIQ* combination vs 40.2% (95% CI, 35.3, 45.2) with Avastin+carbo/pac

  • TECENTRIQ* combination delivered a manageable and generally well-tolerated safety profile.

TECENTRIQ*= TECENTRIQ+Avastin+carboplatin/paclitaxel

Learn more about the safety profile of TECENTRIQ in combination with Avastin+carbo/pac.

2L NSCLC / OAK

Phase III, multicentre, international, randomised, open-label trial evaluating TECENTRIQ against docetaxel in previously treated advanced NSCLC, regardless of PD-L1 expression. A total of 1225 patients were enrolled, with the primary analysis population consisting of the first 850 randomised patients.1,3

IC=tumour-infiltrating immune cell; TC=tumour cell.

  • 55% of patients were alive at 1 year with TECENTRIQ vs 41% with docetaxel (median follow-up time was 21 months)
  • An improvement in median OS was observed with TECENTRIQ vs docetaxel in both non-squamous (15.6 vs 11.2 months; HR=0.73; 95% CI, 0.60, 0.89) and squamous (8.9 vs 7.7 months; HR=0.73; 95% CI, 0.54, 0.98) NSCLC
  • Improved survival was observed with TECENTRIQ at all levels of PD-L1 expression, including for patients with little or no expression (TC and IC <1%: 12.6 vs 8.9 months; HR=0.75)

Learn more about the safety profile of TECENTRIQ as monotherapy.

Bladder Cancer

Tecentriq mUC bladder cancer approval

1L mUC / IMvigor210

Phase II, 2-cohort, multicentre, international, single-arm trial in locally advanced or metastatic urothelial carcinoma (N=438).4,5

TECENTRIQ: DURABLE RESPONSE IN FIRST-LINE, CISPLATIN-INELIGIBLE PATIENTS WHOSE TUMOURS HAVE A PD-L1 EXPRESSION ≥5%


2L mUC / IMvigor211

IMvigor211, patients previously treated with a platinum-containing regimen

Open-label, multicentre, international, randomised study evaluating TECENTRIQ vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who progressed during or following a platinum-containing regimen (N=931).

Primary endpoint: overall survival (OS). Key secondary endpoints: objective response rate (ORR), progression-free survival (PFS) and duration of response (DOR).

The study used a hierarchical testing procedure that required the primary endpoint to be met in the IC2/3 population to claim a positive study outcome.

In IMvigor211 the primary pre-specified OS IC2/3 endpoint was not met.1

  • OS hazard ratio (HR) of 0.87 (95% CI, 0.63, 1.21; P=0.41)

Durable responses demonstrated in the ITT population (median follow-up: 17 months)1,6,7

IC=tumour-infiltrating immune cell.

A 1-year OS of 39% in the ITT population of IMvigor211 was consistent with efficacy results seen in previously reported studies, including a 1-year OS of 37% in Cohort 2 of IMvigor210.

TECENTRIQ showed a favourable safety profile vs chemotherapy.

IMvigor211 data were generally consistent with prior TECENTRIQ studies in patients with locally advanced or metastatic urothelial carcinoma.1

Learn more about the safety profile of TECENTRIQ as monotherapy

2L mUC / SAUL

Phase IIIb, multicentre, international, single-arm study in pretreated patients with locally advanced or metastatic urothelial or non-urothelial carcinoma* of the urinary tract (n=1004).9

Primary endpoints

  • Safety

Secondary endpoints

  • Overall survival (OS)
  • Progression-free survival (PFS)
  • Overall response rate (ORR)
  • Disease control rate (DCR) and duration of response (DoR)

The expert’s view

Prof. Axel Merseburger discusses the recently published SAUL data presented at the European Association of Urology 2019 Congress held in Barcelona, Spain.

 

SAUL: ESTABLISHED SAFETY PROFILE OF TECENTRIQ ACROSS A WIDE mUC  POPULATION WITH A RANGE OF COMORBIDITIES

Safety overview in subgroups of special interest

AE; adverse event, CNS; central nervous system, ECOG; Eastern cooperative oncology group

aAll patients except subgroups excluded from IMvigor211.
bNo treatment-related deaths.
c(3%) treatment-related deaths (dyspnoea, respiratory failure, drug-induced liver injury).
d(0.5%) treatment-related deaths (colitis, intestinal perforation, dyspnoea)

  • ​Low incidence of ≥grade 3 treatment-related adverse events
  • < 1% of patients discontinued treatment due to an immune-related adverse events

SAUL: 46% were alive at 1 year with TECENTRIQ9

For patients with disease characteristics similar to those participating in the IMvigor211* study median overall survival (OS) was 10 months (n= 643).9

CI: Confidence interval
*Defined as the SAUL intent-to-treat population minus the populations excluded from IMvigor211 (open-label, multicentre, international, randomised study).

SAUL TRIAL

  • Disease control rate (DCR) was 40% in previously-treated mUC patients
  • Median duration of response (DoR) was not reached after 12 months follow up

*Non-urothelial carcinoma is not included in the marketing authorisation for TECENTRIQ, and accounted for only 5% of the population in this trial. Presentation of this data is in no way intended to promote the use of TECENTRIQ (atezolizumab) for non-urothelial carcinoma.

Safety Profile

Adverse reactions for TECENTRIQ as monotherapy

The safety of TECENTRIQ as monotherapy is based on pooled data in 3,075 patients across multiple tumour types. The most common adverse reactions (>10%) were fatigue (35.5%), decreased appetite (26%), nausea (23.7%), cough (20.7%), dyspnoea (20.7%), pyrexia (19.9%), diarrhoea (19.8%), rash (19.2%), back pain (15.3%), vomiting (15.3%), asthenia (14.8%), arthralgia (13.9%), pruritus (12.5%) and urinary tract infection (11.7%).

ARs=adverse reactions. *Includes reports of rash, rash maculopapular, erythema, rash pruritic, dermatitis acneiform, eczema, dermatitis, rash erythematous, rash macular, rash papular, skin ulcer, folliculitis, skin exfoliation, erythema multiforme, rash pustular, dermatitis bullous, acne, furuncle, palmar-plantar erythrodysaesthesia syndrome, seborrhoeic dermatitis, dermatitis allergic, drug eruption, rash generalised, erythema of eyelid, skin toxicity, toxic epidermal necrolysis, toxic skin eruption, dermatitis exfoliative, exfoliative rash, eyelid rash, fixed eruption, generalised erythema, rash papulosquamous, and rash vesicular.
 

Low incidence of immune-related ARs across monotherapy studies (N=3178)

Immune-related hypophysitis and nephritis occurred in <0.1% of patients treated with TECENTRIQ monotherapy. Immune-related myocarditis occurred in <0.1% of patients across all TECENTRIQ clinical trials. <1% of patients discontinued treatment due to an immune-related AR.

Adverse reactions for TECENTRIQ as combination therapy

Adverse reactions for TECENTRIQ as combination therapy with nab-paclitaxel

The safety of TECENTRIQ given in combination with nab-paclitaxel has been tested in 452 patients with metastatic TNBC.10 The most common adverse events were similar to those of the nab-paclitaxel group, with no new adverse events identified for the combination of TECENTRIQ and nab-paclitaxel. 

The most common adverse reactions (>20%) were alopecia (56.4%), fatigue (46.7%), nausea (46%), diarrhoea (32.5%), anemia (27.7%), constipation (25%), cough (24.8%), headache (23.2%), peripheral neuropathy (21.7%), neutropenia (20.8%), and decreased appetite (20.1%). 

No new safety risks were identified with TECENTRIQ in combination with nab-paclitaxel.10

AR: adverse reactions

 

Adverse reactions for TECENTRIQ as combination therapy with Avastin + carbo/pac

The safety of TECENTRIQ given in combination with paclitaxel and carboplatin, with or without Avastin, has been evaluated in 793 patients with metastatic NSCLC. The most common adverse reactions (>20%) were peripheral neuropathy (42.6%), nausea (35.6%), anaemia (32.7%), neutropenia (32.4%), fatigue (29.8%), rash (29.8%), constipation (27.2%), decreased appetite (26.2%), diarrhoea (26.0%), thrombocytopenia (24.0%), arthralgia (23.8%).

 

Adverse reactions (ARs) in ≥10% of patients treated with TECENTRIQ + Avastin + carbo/pac and at a higher incidence* than in patients with Avastin + carbo/pac alone.8

*Between-arm difference of ≥5% (all grades) or ≥2% (grades 3-4).
†Three patients receiving TECENTRIQ + Avastin + carbo/pac had grade 5 febrile neutropenia.

Low incidence of immune-related ARs with TECENTRIQ +Avastin+carbo/pac (N=1,202).8

ARs=adverse reactions
‡ The incidence of hypophysitis occurred with TECENTRIQ+Avastin+carbo/pac. All other incidences occurred with TECENTRIQ monotherapy, as no clinically relevant differences were observed with the combination. Immune-related myocarditis occurred in <1.0% of patients across all TECENTRIQ clinical trials. §Bleeding events included haemoptysis, haematuria, pulmonary haemorrhage, cerebral haemorrhage, intestinal haemorrhage, large intestinal haemorrhage and cerebrovascular accident.

Additional Resources

In cancer immunotherapy research, science is changing the score. Starting with the PD-L1 pathway, Roche is taking a dynamic approach to research by exploring how to modulate the antitumour immune response.

For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalised immunotherapy to people with cancer.

This medicinal product is subject to additional monitoring in EMA-approved countries. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

References

  1. TECENTRIQ Summary of Product Characteristics. Roche. August 2019.

  2. TECENTRIQ Core Data Sheet. Version 13.0. Roche. February 2019.

  3. Rittmeyer A, Barlesi F, Waterkamp D, et al; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255-265.

  4. Balar AV, Galsky MD, Rosenberg JE, et al; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. Doi: 10.1016/S0140-6736(16)32455-2.

  5. Loriot Y, Rosenberg JE, Powles T, et al. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): updated OS, safety and biomarkers from the phase III IMvigor210 study. Poster presented at: ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Poster #738P.

  6. Powles T, Durán I, van der Heijden MS, et al; IMvigor211 Study Group. Atezolizumab vs. chemotherapy for platinum-treated advanced urothelial carcinoma.

  7. Powles T, Loriot Y, Durán I, et al. IMvigor211: a phase III randomized study examining atezolizumab vs. chemotherapy for platinum-treated advanced urothelial carcinoma. Presented at: 2nd Special Conference EACR AACR SIC; June 24-27, 2017; Florence, Italy.

  8. Socinski MA, Jotte R, Cappuzzo F, et al; IMpower150 Study Group. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288-2301.

  9. Sternberg CN, et al. Primary results from SAUL, a multinational single-arm safety study of atezolizumab therapy for locally advanced or metastatic urothelial or nonurothelial carcinoma of the urinary tract. Eur Urol (2019), https://doi.org/10.1016/j.eururo.2019.03.015

  10. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):2108-2121.

  11. 2nd interim overall survival analysis presented at ASCO 2019.

Date of preparation: August 2019 l PR/ATEZ/1704/0013d(1)a